MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Seminars in Liver Disease' source. Wed, 08 Feb 2012 16:28:30 +0100 http://www.medworm.com/index.php?rid=5526041&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1297922 Semin Liver Dis 2011; 31: 331-339DOI: 10.1055/s-0031-1297922ABSTRACTThe burden of hepatitis C virus (HCV)-related morbidity and mortality continues to rise. Progression to advanced liver disease among HCV-infected individuals generally requires decades, but we are entering an era where those infected with HCV in the 1970s and 1980s are at significant risk of mortality. Liver disease has overtaken drug-related harm as the major cause of mortality in HCV-infected individuals in many settings. Direct-acting antiviral therapies have provided renewed optimism, but HCV treatment uptake will need to increase markedly to reduce liver disease mortality. This review provides updated information on the natural history of HCV, disease-specific causes of mortality among people with HCV, estimates and p... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5526041 Wed, 21 Dec 2011 05:00:00 +0100 5526041 http://www.medworm.com/index.php?rid=5526040&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1297930 Semin Liver Dis 2011; 31: 420-426DOI: 10.1055/s-0031-1297930ABSTRACTA 51-year-old man from Puerto Rico with Child-Turcotte-Pugh Class C decompensated cirrhosis due to genotype 1a chronic hepatitis C was referred for worsening jaundice and diuretic-resistant ascites. He began experiencing symptoms of hepatic decompensation 5 months prior to referral with new-onset ascites and spontaneous bacterial peritonitis, evolving into diuretic-resistant ascites, increasing jaundice, and a MELD increase from 12 to 29. During his hospitalization, his MELD score increased to >40 from a rapidly increasing international normalized ratio (INR) and evolving type 1 hepatorenal syndrome. Clinically, the patient appeared quite well despite such a high MELD score. After an extensive pretransplant evaluation a... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5526040 Wed, 21 Dec 2011 05:00:00 +0100 5526040 http://www.medworm.com/index.php?rid=5526039&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1297929 Semin Liver Dis 2011; 31: 410-419DOI: 10.1055/s-0031-1297929ABSTRACTNew treatments for chronic hepatitis C combining direct-acting antivirals (DAAs) with pegylated interferon and ribavirin (PEG-IFN/RBV) have dramatically increased the number of patients whose viral load declines to undetectable levels early in treatment. Most go on to achieve a sustained virologic response, but some patients who maintain undetectable levels of virus throughout treatment later relapse during follow-up. These data suggest that hepatitis C virus (HCV) genomes may persist in form(s) that are refractory to eradication by DAAs and PEG-IFN/RBV. Here we examine the molecular biology of HCV replication and review the clinical virology of relapse for clues as to how the virus might survive months of antiviral therap... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5526039 Wed, 21 Dec 2011 05:00:00 +0100 5526039 http://www.medworm.com/index.php?rid=5526038&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1297921 Semin Liver Dis 2011; 31: 327-330DOI: 10.1055/s-0031-1297921© Thieme Medical PublishersArticle in Thieme eJournals:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5526038 Wed, 21 Dec 2011 05:00:00 +0100 5526038 http://www.medworm.com/index.php?rid=5526037&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1297925 Semin Liver Dis 2011; 31: 356-374DOI: 10.1055/s-0031-1297925ABSTRACTHepatitis C virus (HCV) is a hepatotropic RNA virus with an extraordinary propensity to persist in the vast majority of infected individuals. During replication, because of the inherent infidelity of the viral RNA polymerase, each progeny RNA genome contains mutations that lead to a continuous diversification of the viral population. Consequently, HCV circulates in vivo as a quasispecies, which is a dynamic distribution of divergent but closely related genomes subjected to a continuous process of genetic variation, competition, and selection. This genomic heterogeneity confers a remarkable advantage to the viral population allowing for a rapid adaptation to a changing environment when the virus is subject to selective cons... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5526037 Wed, 21 Dec 2011 05:00:00 +0100 5526037 http://www.medworm.com/index.php?rid=5526036&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1297923 Semin Liver Dis 2011; 31: 340-346DOI: 10.1055/s-0031-1297923ABSTRACTThe widespread availability of injectable therapies and increase in illicit injection drug use were responsible for the rapid emergence of hepatitis C virus (HCV) infection in the latter half of the 20th century. Iatrogenic exposures and illicit injection drug use have been the predominant risk factors for HCV transmission worldwide. In developing countries, unsafe therapeutic injection practices appear to be responsible for most infections. In developed countries, donor testing has virtually eliminated transfusion-related infections, but infections transmitted to patients by unsafe injections practices is an emerging problem. Injection drug use is the major risk factor for HCV; incidence remains high among new injectors, ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5526036 Wed, 21 Dec 2011 05:00:00 +0100 5526036 http://www.medworm.com/index.php?rid=5526035&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1297928 This article covers new concepts of treatment of hepatitis C with DAAs and gives an overview of the recent highlights in direct-acting antiviral development.[...]© Thieme Medical PublishersArticle in Thieme eJournals:Table of contents  |  Abstract  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5526035 Wed, 21 Dec 2011 05:00:00 +0100 5526035 http://www.medworm.com/index.php?rid=5526034&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1297927 Semin Liver Dis 2011; 31: 387-398DOI: 10.1055/s-0031-1297927ABSTRACTAccording to the Institute of Medicine, the risk of clinically significant vitamin D deficiency increases at 25-hydroxyvitamin D levels below 20 ng/mL. By this standard, most cirrhotic hepatitis C virus- (HCV-) positive patients and many noncirrhotic patients are vitamin D-deficient. The high prevalence of vitamin D deficiency among HCV patients is a cause for concern for several specific reasons. Classic studies established the importance of vitamin D and calcium in maintaining bone. Vitamin D's beneficial effects on bone are likely to be vital for HCV-infected patients because these individuals have a high prevalence of low bone mineral density. Many pharmaceutical agents reduce bone density and exposure to these drugs m... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5526034 Wed, 21 Dec 2011 05:00:00 +0100 5526034 http://www.medworm.com/index.php?rid=5526033&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1297926 Semin Liver Dis 2011; 31: 375-386DOI: 10.1055/s-0031-1297926ABSTRACTIn recent years, some genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with hepatitis C viral containment, treatment response, and disease progression. IL28B is a gene on chromosome 19, coding for interferon-λ3, and two polymorphisms upstream of this the gene have been strongly associated with clinical outcomes after treatment for the hepatitis C virus (HCV). The IL28B polymorphisms have additionally been associated with spontaneous clearance. The mechanism has yet to be clearly defined, but appears to involve differential responsiveness to interferon signaling between the favorable and unfavorable genotypes. ITPA is a gene on chromosome 20, coding for inosine triph... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5526033 Wed, 21 Dec 2011 05:00:00 +0100 5526033 http://www.medworm.com/index.php?rid=5526032&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1297931 Semin Liver Dis 2011; 31: 427-428DOI: 10.1055/s-0031-1297931© Thieme Medical PublishersArticle in Thieme eJournals:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5526032 Wed, 21 Dec 2011 05:00:00 +0100 5526032 http://www.medworm.com/index.php?rid=5526031&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1297924 Semin Liver Dis 2011; 31: 347-355DOI: 10.1055/s-0031-1297924ABSTRACTHepatocellular carcinoma (HCC) is a common cause of cancer-related mortality. The worldwide incidence of HCC and the hepatitis C virus (HCV) has increased over several decades suggesting an etiologic link. Progress has been made recently in several fields related specifically to HCV and HCC. The epidemiology has been better characterized, surveillance and treatment programs have been instituted, and data have emerged detailing the effect of other risk factors for HCC in patients with HCV. Studies of HCV-related HCC suggest differences in oncogenic potential according to genotype and mutations in the viral sequence. These same mutations are associated with interferon treatment failure, insulin resistance, and expression of ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5526031 Wed, 21 Dec 2011 05:00:00 +0100 5526031 http://www.medworm.com/index.php?rid=5209957&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1286058 Semin Liver Dis 2011; 31: 272-279DOI: 10.1055/s-0031-1286058ABSTRACTSystemic iron homeostasis is regulated by the interaction of the peptide hormone, hepcidin and the iron exporter, ferroportin. Mutations in FPN1, the gene that encodes ferroportin, result in iron-overload disease that shows dominant inheritance and variation in phenotype. The inheritance of ferroportin-linked disorders can be explained by the finding that ferroportin is a multimer and the product of the mutant allele participates in multimer formation. The nature of the ferroportin mutant can explain the variation in phenotype, which is due to either decreased iron export activity or decreased ability to be downregulated by hepcidin. Iron export through ferroportin is determined by the concentration of ferroportin in plasm... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5209957 Wed, 07 Sep 2011 04:00:00 +0100 5209957 http://www.medworm.com/index.php?rid=5209956&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1286059 Semin Liver Dis 2011; 31: 280-292DOI: 10.1055/s-0031-1286059ABSTRACTHereditary hemochromatosis is a genetic disorder of iron overload. Over the past 15 years, significant advances have been made in understanding the molecular pathogenesis of this disorder. First, genetic studies linked this disorder to mutations in several genes, including HFE, transferrin receptor 2 (TFR2), hepcidin (HAMP), ferroportin (SLC40A1), and hemojuvelin (HFE2). Recent progress has generated significant insight into the function of these molecules in systemic iron homeostasis, and has revealed that despite the genetic and phenotypic diversity of hereditary hemochromatosis, there are common pathogenic mechanisms underlying this disease. The common downstream mechanism of iron overload in hereditary hemochromatosis ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5209956 Wed, 07 Sep 2011 04:00:00 +0100 5209956 http://www.medworm.com/index.php?rid=5209955&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1286057 Semin Liver Dis 2011; 31: 260-271DOI: 10.1055/s-0031-1286057ABSTRACTThe growing availability of genetic tests for most inherited iron-overload conditions and our current ability to assess hepatic iron stores, and at a lesser extent, liver fibrosis by noninvasive methods have reduced the need for liver biopsy in patients with hepatic iron excess. Histologic evaluation of the liver remains useful (1) in well-defined genetic iron overload disorders to evaluate associated hepatic damage, (2) in unclassified genetic or acquired iron excess to guide etiologic diagnosis and to establish prognosis, and (3) in research studies for a whole and reliable assessment of the liver. The identification of iron overload, the description of its cellular and lobular distribution, semiquantitative assessment o... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5209955 Wed, 07 Sep 2011 04:00:00 +0100 5209955 http://www.medworm.com/index.php?rid=5209954&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1286053 Semin Liver Dis 2011; 31: 231-232DOI: 10.1055/s-0031-1286053© Thieme Medical PublishersArticle in Thieme eJournals:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5209954 Wed, 07 Sep 2011 04:00:00 +0100 5209954 http://www.medworm.com/index.php?rid=5209953&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1286062 Semin Liver Dis 2011; 31: 319-326DOI: 10.1055/s-0031-1286062ABSTRACTA 15-year-old Caucasian female on human chorionic gonadotropin (HCG) diet presented with fever, cholestasis, coagulopathy, hemolytic anemia, and acute renal dysfunction. Imaging of the biliary system and liver were normal. She responded to intravenous antibiotics, vitamin K and blood transfusions but experienced relapse upon discontinuation of antibiotics. She had remission with reinstitution of antibiotics. Liver biopsy revealed pronounced bile ductular reaction, bridging fibrosis, and hepatocytic anisocytosis and anisonucleosis with degenerative enlarged eosinophilic hepatocytes, suggestive of Wilson disease. Diagnosis of Wilson disease was further established based on the low serum ceruloplasmin, increased urinary and h... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5209953 Wed, 07 Sep 2011 04:00:00 +0100 5209953 http://www.medworm.com/index.php?rid=5209952&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1286060 Semin Liver Dis 2011; 31: 293-301DOI: 10.1055/s-0031-1286060ABSTRACTAdvances in our knowledge of hereditary hemochromatosis (HH) over the past 150 years have revealed new insights into this common genetic disorder. Meticulous family and HLA association studies followed ultimately by cloning of the HFE gene have dramatically changed our understanding of the natural history and manifestations of HH. Cross-sectional studies demonstrated that HH had a highly variable clinical and biochemical penetrance in susceptible individuals of northern European descent. “State-of-the-art” large longitudinal population studies have accurately defined the natural history. We now recognize that HH is not as discreet an entity as previously thought because genetic and environmental modifiers of disease pe... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5209952 Wed, 07 Sep 2011 04:00:00 +0100 5209952 http://www.medworm.com/index.php?rid=5209951&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1286054 Semin Liver Dis 2011; 31: 233-238DOI: 10.1055/s-0031-1286054ABSTRACTWilson disease is an autosomal recessive disorder of copper transport characterized by toxic accumulation of copper in the liver, brain, and other organs. It is lethal if untreated, but effective treatment is available. The broad spectrum of clinical manifestations, including hepatic and neuropsychiatric symptoms, can present over a large age range, contributing to difficulty in recognition of this disease. The diagnosis has traditionally rested on measurements of ceruloplasmin and copper in urine and liver, but it remains a challenge due to ambiguous biochemical results that can overlap with healthy carriers. Although hepatic copper concentration has been the gold standard for diagnosis, direct sequencing of the ATP7B gen... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5209951 Wed, 07 Sep 2011 04:00:00 +0100 5209951 http://www.medworm.com/index.php?rid=5209950&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1286056 Semin Liver Dis 2011; 31: 245-259DOI: 10.1055/s-0031-1286056ABSTRACTNearly a century after Dr. Samuel Alexander Kinnier Wilson composed his doctoral thesis on the pathologic findings of “lenticular degeneration” in the brain associated with cirrhosis of the liver we know that the underlying molecular basis for this autosomal recessive inherited disorder that now bears his name is mutation of a copper transporting ATPase, ATP7B, an intracellular copper transporter mainly expressed in hepatocytes. Loss of ATP7B function is the basis for reduced hepatic biliary copper excretion and reduced incorporation of copper into ceruloplasmin. During the intervening years, there was recognition of the clinical signs, histologic, biochemical features, and mutation analysis of ATP7B that characterize ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5209950 Wed, 07 Sep 2011 04:00:00 +0100 5209950 http://www.medworm.com/index.php?rid=5209949&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1286055 Semin Liver Dis 2011; 31: 239-244DOI: 10.1055/s-0031-1286055ABSTRACTCopper accumulation in the liver is associated with cellular and apoptotic injury. Wilson disease is the most well-characterized disorder of disordered copper metabolism. Other less-common disorders include Indian childhood cirrhosis, endemic Tyrolean infantile cirrhosis, and idiopathic copper toxicosis. The histopathologic spectrum of the liver in Wilson disease is extremely variable and overlaps among the different entities, though this review will focus on the pathology of Wilson disease. The findings lack specificity, although characteristic findings are observed. Unlike other disorders of copper overload, the pathologic changes are typically sequential, ranging from little or no significant findings to cirrhosis with ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5209949 Wed, 07 Sep 2011 04:00:00 +0100 5209949 http://www.medworm.com/index.php?rid=5209948&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1286061 Semin Liver Dis 2011; 31: 302-318DOI: 10.1055/s-0031-1286061ABSTRACTNumerous clinical entities have now been identified to cause pathologic iron accumulation in the liver. Some are well described and have a verified hereditary basis; in others the genetic basis is still speculative, while in several cases nongenetic iron-loading factors are apparent. The non-HFE hemochromatosis syndromes identifies a subgroup of hereditary iron loading disorders that share with classic HFE-hemochromatosis, the autosomal recessive trait, the pathogenic basis (i.e., lack of hepcidin synthesis or activity), and key clinical features. Yet, they are caused by pathogenic mutations in other genes, such as transferrin receptor 2 (TFR2), hepcidin (HAMP), hemojuvelin (HJV), and ferroportin (FPN), and, unlike HFE-hem... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=5209948 Wed, 07 Sep 2011 04:00:00 +0100 5209948 http://www.medworm.com/index.php?rid=4776505&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1276649 Semin Liver Dis 2011; 31: 223-230DOI: 10.1055/s-0031-1276649ABSTRACTLiver involvement in genetic and metabolic disorders may result in intrahepatic accumulation of specific precursors or byproducts, which have distinctive features on light microscopy. The “polyglucosan disorders” are diseases in which polyglucosan (abnormal glycogen with decreased branching) is formed and deposited in various tissues because of decreased or absent glycogen branching enzyme activity. These disorders include Lafora disease (myoclonus epilepsy) and type IV glycogen storage disease. Polyglucosan deposits in both conditions result in ground-glass hepatocellular inclusions resembling those seen in chronic hepatitis B virus infection. In the present report, we describe a case of the rare, adulthood fo... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4776505 Sun, 01 May 2011 23:00:00 +0100 4776505 http://www.medworm.com/index.php?rid=4776504&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1276641 Semin Liver Dis 2011; 31: 215-222DOI: 10.1055/s-0031-1276641ABSTRACTThe field of genomics has entered a new era in which the ability to identify genetic variants that impact complex human traits and disease in an unbiased fashion using genome-wide approaches is widely accessible. To date, the workhorse of these efforts has been the genome-wide association study (GWAS), which has quickly moved from novel to routine, and has provided key insights into aspects of the underlying allelic architecture of complex traits. The main lesson learned from the early GWAS efforts is that though many disease-associated variants are often discovered, most have only a minor effect on disease, and in total explain only a small amount of the apparent heritability. Here we provide a brief overview of the genet... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4776504 Sun, 01 May 2011 23:00:00 +0100 4776504 http://www.medworm.com/index.php?rid=4776503&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1276648 Semin Liver Dis 2011; 31: 208-214DOI: 10.1055/s-0031-1276648ABSTRACTThe genetic background of patients with liver diseases modulates hepatic injury, with some individuals being predisposed to better defenses and regenerative capacity. In this review, we focus our description of this phenomenon on inherited disorders affecting the liver, with a particular emphasis on Wilson disease (WD), genetic hemochromatosis, and α-1 anti-trypsin disease (A1-AT). Wide variations in the clinical phenotype of WD may in part be related to the mutations of the ATP7B genotype, though modifier genes and environmental factors also likely play an important role. There is also a significant variability in the expression of iron overload in patients with genetic hemochromatosis that are homozygous for the C28... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4776503 Sun, 01 May 2011 23:00:00 +0100 4776503 http://www.medworm.com/index.php?rid=4776502&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1276647 Semin Liver Dis 2011; 31: 188-207DOI: 10.1055/s-0031-1276647ABSTRACTGenetic variants within the major histocompatibility complex (MHC) on chromosome 6 have been shown to confer risk for primary sclerosing cholangitis (PSC) ~30 years ago. However, robust genetic associations outside this genetic region have been difficult to establish. By genome-wide association analysis, a surprising large overlap of genetic risk loci outside of the MHC with prototypical autoimmune diseases has been recognized. In this article, we review the present knowledge of susceptibility loci in PSC, by assessing the robustness of the findings and speculating on potential mechanistic roles of predicted risk genes in PSC pathogenesis. We suggest a model where the primary insult is likely to resemble the tissue injury ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4776502 Sun, 01 May 2011 23:00:00 +0100 4776502 http://www.medworm.com/index.php?rid=4776501&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1276646 Semin Liver Dis 2011; 31: 173-187DOI: 10.1055/s-0031-1276646ABSTRACTHepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are two leading causes of cancer death in the world. Liver carcinogenesis is driven by genetic alterations in combination with viral and environmental factors. β-catenin and P53 mutations represent the two main genetic alterations described in HCC, and P53 and KRAS mutations in CC, but rare genetic alterations could be particularly valuable if they constitute drug-able targets (such as PIK3CA or EGFR mutations). Recent progress using global genomic analysis has highlighted the marked genetic heterogeneity of this disease and this approach has also been used to assess prognosis or refine the diagnosis. The validation of sorafenib as the first targeted therapy u... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4776501 Sun, 01 May 2011 23:00:00 +0100 4776501 http://www.medworm.com/index.php?rid=4776500&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1276645 Semin Liver Dis 2011; 31: 157-172DOI: 10.1055/s-0031-1276645ABSTRACTGallstone disease affects almost 20% of individuals in Westernized countries. As its incidence in the developing countries is rising considerably, currently, it is the second most common gastroenterological condition worldwide. Gallstone formation is driven by an interaction between genetic and environmental risk factors. Previous studies have demonstrated that the genetic background accounts for ~25% of the total disease risk. Linkage and case-control studies of candidate genes and recent genome-wide studies have identified multiple lithogenic genes, in particular the hepatocanalicular cholesterol transporter ABCG5/G8 and the bilirubin conjugating enzyme UGT1A1, as major genetic determinants of gallstones in humans. In th... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4776500 Sun, 01 May 2011 23:00:00 +0100 4776500 http://www.medworm.com/index.php?rid=4776499&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1276644 Semin Liver Dis 2011; 31: 147-156DOI: 10.1055/s-0031-1276644ABSTRACTPrimary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that has a prevalence of 1 in 1000 women over the age of 40. Treatment is presently limited to ursodeoxycholic acid, a hydrophilic bile acid that has nonspecific, choleretic, effects in cholestatic liver disease. PBC has strong autoimmune features, including highly specific loss of tolerance to a ubiquitous mitochondrial antigen. Both environmental and genetic factors are considered important in the pathogenesis of disease. Prior to the advent of genome-wide association studies, only class II human leucocyte antigen (HLA) loci (HLA-DRB1*08, *11, and *13) had been reproducibly shown to associate with disease. Non-HLA loci were suggested for several genes... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4776499 Sun, 01 May 2011 23:00:00 +0100 4776499 http://www.medworm.com/index.php?rid=4776498&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1276643 Semin Liver Dis 2011; 31: 128-146DOI: 10.1055/s-0031-1276643ABSTRACTExcess alcohol consumption with consequent alcoholic liver disease (ALD) and metabolic syndrome-related nonalcoholic fatty liver disease (NAFLD) are recognized as the most common causes of liver dysfunction worldwide. However, although the majority of heavy drinkers and individuals with obesity/insulin resistance will develop steatosis, only a minority progress to steatohepatitis, fibrosis, and cirrhosis. Both ALD and NAFLD are best considered complex disease traits where subtle interpatient genetic variations and environment interact to produce disease phenotype and determine disease progression. A decade after the sequencing of the human genome, the development of technologies to support the comprehensive study of genomi... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4776498 Sun, 01 May 2011 23:00:00 +0100 4776498 http://www.medworm.com/index.php?rid=4776497&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1276642 Semin Liver Dis 2011; 31: 115-127DOI: 10.1055/s-0031-1276642ABSTRACTThe outcome of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are heterogeneous, ranging from an asymptomatic self-limiting infection to cirrhosis and hepatocellular carcinoma. Several viral environmental and demographic variables have been identified as determinants of disease outcome, but these fail to explain a large proportion of the variability. Evidence from twin studies suggests that the host genetic background is an important contributor to disease outcome. Identification of genes that influence the outcome of infection has been attempted using a wide spectrum of approaches including candidate gene disease association studies, genome-wide scanning in affected sibling pairs and most recently genome-w... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4776497 Sun, 01 May 2011 23:00:00 +0100 4776497 http://www.medworm.com/index.php?rid=4776496&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1276640 Semin Liver Dis 2011; 31: 111-114DOI: 10.1055/s-0031-1276640© Thieme Medical PublishersArticle in Thieme eJournals:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4776496 Sun, 01 May 2011 23:00:00 +0100 4776496 http://www.medworm.com/index.php?rid=4508474&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1272838 Semin Liver Dis 2011; 31: 104-110DOI: 10.1055/s-0031-1272838ABSTRACTThe authors present an interesting case of a 60-year-old man who underwent right hepatectomy for a diagnosis of hepatocellular carcinoma (HCC) on a background of noncirrhotic chronic hepatitis C. Pathologic examination confirmed the presence of HCC near the porta hepatis, which invaded the right portal vein branch. In addition, a well-demarcated 13.5 × 7.8 × 4.0 cm yellow and firm area upstream of the HCC was noted. This yellow area corresponded to a tumoral ductular proliferation, which cytologically was extremely bland, but invaded portal tracts and the adjacent liver parenchyma. This tumoral proliferation mimicked ductular reaction, except that it had more anastomosing structures and was associated with abundant hyali... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4508474 Tue, 22 Feb 2011 00:00:00 +0100 4508474 http://www.medworm.com/index.php?rid=4508473&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1272837 Semin Liver Dis 2011; 31: 091-103DOI: 10.1055/s-0031-1272837ABSTRACTIn this review, the authors focus on the use of immunohistochemistry to characterize the different types and subtypes of benign hepatocellular nodules. They describe the classical and currently accepted features leading to the easy and formal diagnosis of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA). In addition, they report some atypical features and difficulties in the interpretation of section staining analyses, which represent important parameters for pathologists. A significant contribution of molecular biology to the characterization of FNH has been to reclassify some cases of FNH as inflammatory HCA. Furthermore, the pattern of overexpression of glutamine synthetase (GS), a target gene of β-... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4508473 Tue, 22 Feb 2011 00:00:00 +0100 4508473 http://www.medworm.com/index.php?rid=4508472&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1272836 Semin Liver Dis 2011; 31: 082-090DOI: 10.1055/s-0031-1272836ABSTRACTThe liver biopsy specimen represents valuable material for the assessment of fibrosis and cirrhosis. Despite limitations related to sampling and interpretation, histologic examination remains the gold standard for staging chronic liver diseases. Hepatic fibrosis is currently viewed as a dynamic process that may often regress after successful treatment of chronic liver diseases. Even the excess fibrous tissue of cirrhotic livers may sometimes regress over time. Distinguishing between the amount of hepatic fibrosis and the disease stage is important for the assessment of the effects of antifibrotic treatments. Recent studies suggest that the proportion of the liver biopsy specimen occupied by collagen is correlated with the ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4508472 Tue, 22 Feb 2011 00:00:00 +0100 4508472 http://www.medworm.com/index.php?rid=4508471&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1272834 Semin Liver Dis 2011; 31: 071-081DOI: 10.1055/s-0031-1272834ABSTRACTAllograft dysfunction with clinical, serologic, and histologic features resembling autoimmune hepatitis (AIH) may develop in pediatric and adult patients who have received a liver transplant (LT) for end-stage diseases other than AIH. This condition is now known as de novo AIH, although its pathophysiology is still uncertain and whether it represents a specific type of rejection or a genuine form of AIH is under debate. The occurrence of de novo AIH seems to be unrelated to the etiology of the disease necessitating liver transplantation, but it has been correlated with antiviral treatment in cases of hepatitis C virus (HCV) infection recurring after LT. Several investigators have reported adverse outcome of de novo AIH, in... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4508471 Tue, 22 Feb 2011 00:00:00 +0100 4508471 http://www.medworm.com/index.php?rid=4508470&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1272835 Semin Liver Dis 2011; 31: 061-070DOI: 10.1055/s-0031-1272835ABSTRACTFibrolamellar carcinoma is a rare primary malignant liver neoplasm that usually affects adolescents and young adults with no underlying liver disease. Morphologically, the tumor cells resemble oncocytic hepatocytes arranged in cords with a stroma of lamellated collagen fibers. Immunohistochemical studies have found that fibrolamellar carcinomas express markers associated with both biliary (CK7 and epithelial membrane antigen) and hepatocytic (heppar-1and glypican-3) differentiation, as well as markers associated with hepatic progenitor cells (CK19 and EpCAM) and stem cells (CD133 and CD44). Genetic studies show fewer alterations compared with classic hepatocellular carcinoma. Pooled data from comparative genomic hybridizat... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4508470 Tue, 22 Feb 2011 00:00:00 +0100 4508470 http://www.medworm.com/index.php?rid=4508469&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1272839 Semin Liver Dis 2011; 31: 049-060DOI: 10.1055/s-0031-1272839ABSTRACTCholangiocarcinomas are malignant tumors that derive from cholangiocytes of small intrahepatic bile ducts or bile ductules (intrahepatic cholangiocarcinoma; ICC), or of large hilar or extrahepatic bile ducts (extrahepatic cholangiocarcinoma; ECC). ICC and ECC differ in morphology, pathogenesis, risk factors, treatment, and prognosis. This review focuses on ICC, which is rising in incidence with the emergence of hepatitis C virus (HCV) infection as a risk factor. The authors examined 73 ICC, which were resected at The Mount Sinai Medical Center in New York City, and reviewed the literature. The tumors were categorized into classical and nonclassical ICCs based on histopathology. Classical ICCs (54.8%) were characterized by ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4508469 Tue, 22 Feb 2011 00:00:00 +0100 4508469 http://www.medworm.com/index.php?rid=4508468&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1272833 Semin Liver Dis 2011; 31: 033-048DOI: 10.1055/s-0031-1272833ABSTRACTPrimary hepatothiasis (HL) and recurrent pyogenic cholangitis (RPC) are two terms describing the different aspects of the same disease, with HL emphasizing the pathologic changes and RPC emphasizing the clinical presentation and suppurative inflammation. It is predominantly a disease of the Far East. In the 1960s, it was the third most common cause of emergency abdominal surgery at a university hospital in Hong Kong. Thereafter, its incidence has decreased considerably, possibly due to improved standards of living and Westernized diet. Clinically, patients may present acutely with recurrent bacterial cholangitis and its possible complications, such as liver abscess and septicemic shock, or with chronic complications, such ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4508468 Tue, 22 Feb 2011 00:00:00 +0100 4508468 http://www.medworm.com/index.php?rid=4508467&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1272832 Semin Liver Dis 2011; 31: 011-032DOI: 10.1055/s-0031-1272832ABSTRACTIn most cholangiopathies, liver diseases of different etiologies in which the biliary epithelium is the primary target in the pathogenic sequence, the central mechanism involves inflammation. Inflammation, characterized by pleomorphic peribiliary infiltrate containing fibroblasts, macrophages, lymphocytes, as well as endothelial cells and pericytes, is associated to the emergence of “reactive cholangiocytes.” These biliary cells do not possess bile secretory functions, are in contiguity with terminal cholangioles, and are of a less-differentiated phenotype. They have acquired several mesenchymal properties, including motility and ability to secrete a vast number of proinflammatory chemo/cytokines and growth fac... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4508467 Tue, 22 Feb 2011 00:00:00 +0100 4508467 http://www.medworm.com/index.php?rid=4508466&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1272831 Semin Liver Dis 2011; 31: 003-010DOI: 10.1055/s-0031-1272831ABSTRACTProgressive familial intrahepatic cholestatic diseases encompass a group of autosomal recessive hereditary diseases, which usually present in infancy or childhood, with cholestasis of hepatocellular origin. The currently preferred nomenclature for the three PFIC disorders that have been characterized to date is FIC1 deficiency, BSEP deficiency, and MDR3 deficiency, relating to mutations in the specific genes involved in bile acid formation and transport. Since the first description of these diseases, extensive clinical, biochemical, and molecular studies have increased our understanding of the features specific to each one of them. This review focuses mainly on the liver histology, summarizing their characteristic patholog... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4508466 Tue, 22 Feb 2011 00:00:00 +0100 4508466 http://www.medworm.com/index.php?rid=4508465&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0031-1272830 Semin Liver Dis 2011; 31: 001-002DOI: 10.1055/s-0031-1272830© Thieme Medical PublishersArticle in Thieme eJournals:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4508465 Tue, 22 Feb 2011 00:00:00 +0100 4508465 http://www.medworm.com/index.php?rid=4083290&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1267542 Semin Liver Dis 2010; 30: 422-428DOI: 10.1055/s-0030-1267542ABSTRACTPrimary hepatic signet ring cell neuroendocrine tumor is extremely rare and is characterized by distinct intracytoplasmic hyaline vacuoles that are mucin negative and cytokeratin positive. The unique histological features may cause difficulty in diagnosis and delay patient care. Here the authors report a 49-year-old man with an incidental finding of a 2.7 cm liver mass in the absence of chronic liver disease. The resected tumor was grossly unencapsulated but well demarcated with friable tissue texture. Microscopically, the entire tumor consisted of sheets of monotonous cells separated by delicate microvasculature. The tumor cells had granular chromatin, inconspicuous nucleoli, and eosinophilic cytoplasm. Many of the tumor ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083290 Mon, 18 Oct 2010 23:00:00 +0100 4083290 http://www.medworm.com/index.php?rid=4083289&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1267541 Semin Liver Dis 2010; 30: 411-421DOI: 10.1055/s-0030-1267541ABSTRACTLiver transplantation has rapidly advanced from an experimental therapy to a mainstream treatment option for a wide range of acute and chronic liver diseases. Indications for liver transplant have evolved to include previously contraindicated conditions such as hepatocellular carcinoma and alcohol-related liver disease. Cirrhosis from chronic hepatitis C infection remains the most common indication today. Multidisciplinary evaluation for liver transplantation is intended to confirm the patient's suitability and identify the appropriate timing of transplant, although the latter is problematic as a result of the ongoing donor organ shortage. Deceased liver donors have been increasing in number, but increasing donor age has b... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083289 Mon, 18 Oct 2010 23:00:00 +0100 4083289 http://www.medworm.com/index.php?rid=4083288&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1267540 Semin Liver Dis 2010; 30: 402-410DOI: 10.1055/s-0030-1267540ABSTRACTHepatocyte injury is ubiquitous in clinical practice, and the mode of cell death associated with this injury is often apoptosis, especially by death receptors. Information from experimental systems demonstrates that hepatocyte apoptosis is sufficient to cause liver hepatic fibrogenesis. The mechanisms linking hepatocyte apoptosis to hepatic fibrosis remain incompletely understood, but likely relate to engulfment of apoptotic bodies by professional phagocytic cells and stellate cells, and release of mediators by cells undergoing apoptosis. Inhibition of apoptosis with caspase inhibitors has demonstrated beneficial effects in murine models of hepatic fibrosis. Recent studies implicating Toll-like receptor 9 in liver injury a... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083288 Mon, 18 Oct 2010 23:00:00 +0100 4083288 http://www.medworm.com/index.php?rid=4083287&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1267539 Semin Liver Dis 2010; 30: 391-401DOI: 10.1055/s-0030-1267539ABSTRACTNonalcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease affecting both adults and children in the United States and many other parts of the world. NAFLD encompasses a wide spectrum of conditions associated with overaccumulation of lipids in the liver. It is strongly associated with obesity and insulin resistance and has been growingly recognized as an independent risk factor for cardiovascular disease. In this review, recently uncovered novel aspects of the molecular events responsible for the development and progression of this highly prevalent and potentially serious disease are discussed. These studies bring new insights that may significantly impact the clinical approach to p... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083287 Mon, 18 Oct 2010 23:00:00 +0100 4083287 http://www.medworm.com/index.php?rid=4083286&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1267538 Semin Liver Dis 2010; 30: 378-390DOI: 10.1055/s-0030-1267538ABSTRACTHepatic steatosis is now understood to play an important role in the development of advanced liver disease. Alcoholic and nonalcoholic fatty liver each begin with the accumulation of lipids in the liver. Lipid accumulation in the liver can occur through maladaptations of fatty acid uptake (either through dietary sources or from fat tissue), fatty acid synthesis, fatty acid oxidation, or export of lipids from the liver. Alterations in mechanisms of fatty acid uptake through both dietary uptake and lipolysis in adipose tissue can contribute to the pathogenesis of both disorders, as can effects on fatty acid transporters. Effects on lipid synthesis in alcoholic and nonalcoholic fatty liver involve the endoplasmic reticulum (E... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083286 Mon, 18 Oct 2010 23:00:00 +0100 4083286 http://www.medworm.com/index.php?rid=4083285&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1267537 Semin Liver Dis 2010; 30: 361-377DOI: 10.1055/s-0030-1267537ABSTRACTSeveral national and international guidelines have been published in the last years focusing on the problem of how to best treat patients with chronic hepatitis B virus (HBV) infection. Therapy with interferon or nucleos(t)ide analogues has been shown to be most effective in suppressing HBV deoxyribonucleic acid (DNA) levels and preventing fibrosis progression herby also reducing the risk of hepatocellular carcinoma (HCC). However even suppression of viral replication below the limit of detection does not prevent HCC development although fibrosis can be stopped. Thus, improvement of therapeutic strategies and the establishment of more sensitive markers that may help to decide when therapy should be initiated and stopped re... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083285 Mon, 18 Oct 2010 23:00:00 +0100 4083285 http://www.medworm.com/index.php?rid=4083284&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1267536 Semin Liver Dis 2010; 30: 348-360DOI: 10.1055/s-0030-1267536ABSTRACTHepatitis C infection has evolved in the past quarter century from a newly recognized entity without a known pathogen (non-A, non-B hepatitis) to one of the world's most prevalent causes of liver disease, an important source for hepatocellular carcinoma, and the major indication for liver transplantation. It is caused by a virus with a complex replication cycle that occurs in multiple genotypes, of which the four most prevalent (1, 2, 3, and 4) exhibit differences in clinical behavior and responses to therapy. Chronic hepatitis C virus (HCV) in particular has evolved from a disease with no known treatment to one with several primary treatment options, none of which is uniformly effective, and a growing list of secondary tr... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083284 Mon, 18 Oct 2010 23:00:00 +0100 4083284 http://www.medworm.com/index.php?rid=4083283&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1267535 Semin Liver Dis 2010; 30: 333-347DOI: 10.1055/s-0030-1267535ABSTRACTWith the advent of efficient systems to propagate the hepatitis C virus (HCV) in cultured cells important new discoveries have been made. For instance, several molecules required for HCV infection of hepatocytes have been identified and first insights into the entry pathway have been gained. Ribonucleic acid (RNA) replication and virion assembly were found to be tightly linked to lipid metabolism and numerous host factors contributing to viral replication have been identified. Some of them such as cyclophilin A or microRNA-122 are attractive targets for antiviral therapy as are the viral serine-type protease residing in nonstructural protein 3 (NS3) and the NS5B RNA-dependent RNA polymerase. More recently, the viral phosph... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083283 Mon, 18 Oct 2010 23:00:00 +0100 4083283 http://www.medworm.com/index.php?rid=4083282&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1267534 Semin Liver Dis 2010; 30: 319-332DOI: 10.1055/s-0030-1267534ABSTRACTHepatitis A and hepatitis C viruses (HAV and HCV) are both positive-strand ribonucleic acid (RNA) viruses with hepatotropic lifestyles. Despite several important differences, they share many biological and molecular features and similar genome replication schemes. Despite this, HAV infections are usually effectively controlled by the host with elimination of the virus, whereas HCV most often is able to establish lifelong persistent infection. The mechanisms underlying this difference are unknown. The cellular helicases RIG-I and MDA5, and Toll-like receptor 3, are pattern recognition receptors that sense virus-derived RNAs within hepatocytes in the liver. Activation of these receptors leads to their interaction with specif... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083282 Mon, 18 Oct 2010 23:00:00 +0100 4083282 http://www.medworm.com/index.php?rid=4083281&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1267730 Semin Liver Dis 2010; 30: 311-318DOI: 10.1055/s-0030-1267730© Thieme Medical PublishersArticle in Thieme eJournals:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083281 Mon, 18 Oct 2010 23:00:00 +0100 4083281 http://www.medworm.com/index.php?rid=3774038&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1262516 Semin Liver Dis 2010; 30: 302-309DOI: 10.1055/s-0030-1262516© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3774038 Thu, 22 Jul 2010 05:48:33 +0100 3774038 http://www.medworm.com/index.php?rid=3774037&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1262515 We present a patient with HBeAg-negative chronic hepatitis B, in whom significant regression of hepatic fibrosis was achieved after a lengthy antiviral treatment. A liver biopsy specimen obtained at initiation of treatment showed chronic hepatitis B with mild activity (histologic activity index: 7) and marked fibrosis (stage 4, in a scale of 0 to 6). A second biopsy specimen, obtained 10 years later, demonstrated almost complete resolution of necroinflammatory activity and fibrosis. One year after the second biopsy, seroconversion from HBsAg positive to anti-HBs positive status was achieved, and antiviral treatment was discontinued. This case is illustrative of the significant histologic improvement that can be accomplished in chronic hepatitis B when viral activity is suppressed long term... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3774037 Thu, 22 Jul 2010 05:48:33 +0100 3774037 http://www.medworm.com/index.php?rid=3774036&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1255357 Semin Liver Dis 2010; 30: 288-295DOI: 10.1055/s-0030-1255357ABSTRACTLiver regeneration has traditionally been investigated in mammalian models. Recent technological developments in mouse genetics have greatly enhanced the resolving power of these studies. In addition, the zebrafish system has emerged as a complementary genetic system to study liver regeneration. One of the most promising attributes of the zebrafish system is its amenability to large-scale screens including genetic and chemical screens. Also, as our understanding of liver development is becoming more detailed, it is important to evaluate the commonalities and differences between organ development and regeneration.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Sem... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3774036 Thu, 22 Jul 2010 05:48:33 +0100 3774036 http://www.medworm.com/index.php?rid=3774035&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1255356 Semin Liver Dis 2010; 30: 271-287DOI: 10.1055/s-0030-1255356ABSTRACTIron is a crucially important element in normal cellular function and thus the regulation of iron homeostasis is tightly controlled. When this regulation is disrupted, for instance in hereditary hemochromatosis, abnormal intestinal absorption of iron leads to cellular toxicity, tissue injury, and organ fibrosis via the deposition of this iron in parenchymal cells of a number of different organs such as the heart, pancreas, and liver. Iron-generated oxyradicals contribute to the peroxidation of lipid membranes leading to organelle fragility and cellular toxicity. This process is thought to contribute to hepatocellular necrosis and/or apoptosis in the liver with the subsequent activation of hepatic stellate cells and the dev... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3774035 Thu, 22 Jul 2010 05:48:33 +0100 3774035 http://www.medworm.com/index.php?rid=3774034&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1255355 Semin Liver Dis 2010; 30: 258-270DOI: 10.1055/s-0030-1255355ABSTRACTLiver injury causes vascular disorganization and local tissue hypoxia starting early in disease course. In this context, hypoxia acts not only as an aggravating factor of cell damage and inflammation, but also as an inhibitor of liver regeneration, a major stimulus of angiogenesis and fibrogenesis, and a promoter of liver carcinogenesis. Many of the effects of hypoxia are mediated by hypoxia-inducible factor-1α (HIF-1α), an oxygen-sensitive transcription factor. Compared to cells in the periportal area, intralobular hepatic stellate cells (HSCs) are more responsive to hypoxia and like other pericytes play a key role in angiogenesis through interactions with endothelial cells platelet-derived growth factor (PGDF) ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3774034 Thu, 22 Jul 2010 05:48:33 +0100 3774034 http://www.medworm.com/index.php?rid=3774033&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1255354 Semin Liver Dis 2010; 30: 245-257DOI: 10.1055/s-0030-1255354ABSTRACTMacrophages are found in close proximity with collagen-producing myofibroblasts and indisputably play a key role in fibrosis. They produce profibrotic mediators that directly activate fibroblasts, including transforming growth factor-β1 and platelet-derived growth factor, and control extracellular matrix turnover by regulating the balance of various matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases. Macrophages also regulate fibrogenesis by secreting chemokines that recruit fibroblasts and other inflammatory cells. With their potential to act in both a pro- and antifibrotic capacity, as well as their ability to regulate the activation of resident and recruited myofibroblasts, macrophages and... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3774033 Thu, 22 Jul 2010 05:48:33 +0100 3774033 http://www.medworm.com/index.php?rid=3774032&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1255353 Semin Liver Dis 2010; 30: 232-244DOI: 10.1055/s-0030-1255353ABSTRACTInflammation is strongly associated with chronic hepatic injury and the ensuing wound-healing process. Recent evidence from mouse models and human studies implicates Toll-like receptors (TLRs) as important regulators of the inflammatory response and a functional link between inflammation and fibrosis in the chronically injured liver. Here, we review mechanisms by which TLR4 and TLR4 ligands from the intestinal microbiota contribute to hepatic injury, inflammation, hepatic stellate cell activation, and fibrosis.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3774032 Thu, 22 Jul 2010 05:48:33 +0100 3774032 http://www.medworm.com/index.php?rid=3774031&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1255352 Semin Liver Dis 2010; 30: 226-231DOI: 10.1055/s-0030-1255352ABSTRACTFibrosis is a common feature of chronic liver injury and is initiated by cell death inside the liver. Hepatocyte death results in apoptotic bodies and other cellular debris, which are phagocytosed by hepatic stellate cells (HSCs), resulting in their activation, proliferation, differentiation, and matrix deposition. This profibrotic effect of cellular death is balanced by an antifibrotic effect of HSC death. Many HSC survival signals are obtained from the extracellular matrix, and active proapoptotic signals are provided by immune cells, particularly natural killer (NK) cells. Quiescent HSCs are relatively resistant to apoptotic signals but become sensitive after activation. The important role of NK cells in inducing HSC ap... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3774031 Thu, 22 Jul 2010 05:48:33 +0100 3774031 http://www.medworm.com/index.php?rid=3774030&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1255351 Semin Liver Dis 2010; 30: 215-225DOI: 10.1055/s-0030-1255351ABSTRACTChemokines are a class of small chemotactic molecules with cytokine-like functions, which are well known to orchestrate inflammatory responses within different organs. Overall, more than 50 ligands and 19 receptors belong to the network. In recent years, accumulating functional and genetic evidence suggests that chemokines play a critical role in acute and chronic liver diseases, mediating the infiltration of immune cells (monocytes, T-cells) into the injured liver along a concentration gradient. However, chemokines can also directly affect the biology of liver resident cells, such as hepatic stellate cells and hepatocytes during inflammatory and fibrogenic tissue responses. Although the chemokine system has long been cons... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3774030 Thu, 22 Jul 2010 05:48:33 +0100 3774030 http://www.medworm.com/index.php?rid=3774029&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1255350 Semin Liver Dis 2010; 30: 211-214DOI: 10.1055/s-0030-1255350© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3774029 Thu, 22 Jul 2010 05:48:33 +0100 3774029 http://www.medworm.com/index.php?rid=4083300&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1262516 Semin Liver Dis 2010; 30: 302-309DOI: 10.1055/s-0030-1262516© Thieme Medical PublishersArticle in Thieme eJournals:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083300 Tue, 20 Jul 2010 23:00:00 +0100 4083300 http://www.medworm.com/index.php?rid=4083299&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1262515 We present a patient with HBeAg-negative chronic hepatitis B, in whom significant regression of hepatic fibrosis was achieved after a lengthy antiviral treatment. A liver biopsy specimen obtained at initiation of treatment showed chronic hepatitis B with mild activity (histologic activity index: 7) and marked fibrosis (stage 4, in a scale of 0 to 6). A second biopsy specimen, obtained 10 years later, demonstrated almost complete resolution of necroinflammatory activity and fibrosis. One year after the second biopsy, seroconversion from HBsAg positive to anti-HBs positive status was achieved, and antiviral treatment was discontinued. This case is illustrative of the significant histologic improvement that can be accomplished in chronic hepatitis B when viral activity is suppressed long term... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083299 Tue, 20 Jul 2010 23:00:00 +0100 4083299 http://www.medworm.com/index.php?rid=4083298&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1255357 Semin Liver Dis 2010; 30: 288-295DOI: 10.1055/s-0030-1255357ABSTRACTLiver regeneration has traditionally been investigated in mammalian models. Recent technological developments in mouse genetics have greatly enhanced the resolving power of these studies. In addition, the zebrafish system has emerged as a complementary genetic system to study liver regeneration. One of the most promising attributes of the zebrafish system is its amenability to large-scale screens including genetic and chemical screens. Also, as our understanding of liver development is becoming more detailed, it is important to evaluate the commonalities and differences between organ development and regeneration.[...]© Thieme Medical PublishersArticle in Thieme eJournals:Table of contents  |  Abstract  |  Full tex... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083298 Tue, 20 Jul 2010 23:00:00 +0100 4083298 http://www.medworm.com/index.php?rid=4083297&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1255356 Semin Liver Dis 2010; 30: 271-287DOI: 10.1055/s-0030-1255356ABSTRACTIron is a crucially important element in normal cellular function and thus the regulation of iron homeostasis is tightly controlled. When this regulation is disrupted, for instance in hereditary hemochromatosis, abnormal intestinal absorption of iron leads to cellular toxicity, tissue injury, and organ fibrosis via the deposition of this iron in parenchymal cells of a number of different organs such as the heart, pancreas, and liver. Iron-generated oxyradicals contribute to the peroxidation of lipid membranes leading to organelle fragility and cellular toxicity. This process is thought to contribute to hepatocellular necrosis and/or apoptosis in the liver with the subsequent activation of hepatic stellate cells and the dev... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083297 Tue, 20 Jul 2010 23:00:00 +0100 4083297 http://www.medworm.com/index.php?rid=4083296&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1255355 Semin Liver Dis 2010; 30: 258-270DOI: 10.1055/s-0030-1255355ABSTRACTLiver injury causes vascular disorganization and local tissue hypoxia starting early in disease course. In this context, hypoxia acts not only as an aggravating factor of cell damage and inflammation, but also as an inhibitor of liver regeneration, a major stimulus of angiogenesis and fibrogenesis, and a promoter of liver carcinogenesis. Many of the effects of hypoxia are mediated by hypoxia-inducible factor-1α (HIF-1α), an oxygen-sensitive transcription factor. Compared to cells in the periportal area, intralobular hepatic stellate cells (HSCs) are more responsive to hypoxia and like other pericytes play a key role in angiogenesis through interactions with endothelial cells via platelet-derived growth factor (PG... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083296 Tue, 20 Jul 2010 23:00:00 +0100 4083296 http://www.medworm.com/index.php?rid=4083295&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1255354 Semin Liver Dis 2010; 30: 245-257DOI: 10.1055/s-0030-1255354ABSTRACTMacrophages are found in close proximity with collagen-producing myofibroblasts and indisputably play a key role in fibrosis. They produce profibrotic mediators that directly activate fibroblasts, including transforming growth factor-β1 and platelet-derived growth factor, and control extracellular matrix turnover by regulating the balance of various matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases. Macrophages also regulate fibrogenesis by secreting chemokines that recruit fibroblasts and other inflammatory cells. With their potential to act in both a pro- and antifibrotic capacity, as well as their ability to regulate the activation of resident and recruited myofibroblasts, macrophages and... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083295 Tue, 20 Jul 2010 23:00:00 +0100 4083295 http://www.medworm.com/index.php?rid=4083294&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1255353 Semin Liver Dis 2010; 30: 232-244DOI: 10.1055/s-0030-1255353ABSTRACTInflammation is strongly associated with chronic hepatic injury and the ensuing wound-healing process. Recent evidence from mouse models and human studies implicates Toll-like receptors (TLRs) as important regulators of the inflammatory response and a functional link between inflammation and fibrosis in the chronically injured liver. Here, we review mechanisms by which TLR4 and TLR4 ligands from the intestinal microbiota contribute to hepatic injury, inflammation, hepatic stellate cell activation, and fibrosis.[...]© Thieme Medical PublishersArticle in Thieme eJournals:Table of contents  |  Abstract  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083294 Tue, 20 Jul 2010 23:00:00 +0100 4083294 http://www.medworm.com/index.php?rid=4083293&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1255352 Semin Liver Dis 2010; 30: 226-231DOI: 10.1055/s-0030-1255352ABSTRACTFibrosis is a common feature of chronic liver injury and is initiated by cell death inside the liver. Hepatocyte death results in apoptotic bodies and other cellular debris, which are phagocytosed by hepatic stellate cells (HSCs), resulting in their activation, proliferation, differentiation, and matrix deposition. This profibrotic effect of cellular death is balanced by an antifibrotic effect of HSC death. Many HSC survival signals are obtained from the extracellular matrix, and active proapoptotic signals are provided by immune cells, particularly natural killer (NK) cells. Quiescent HSCs are relatively resistant to apoptotic signals but become sensitive after activation. The important role of NK cells in inducing HSC ap... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083293 Tue, 20 Jul 2010 23:00:00 +0100 4083293 http://www.medworm.com/index.php?rid=4083292&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1255351 Semin Liver Dis 2010; 30: 215-225DOI: 10.1055/s-0030-1255351ABSTRACTChemokines are a class of small chemotactic molecules with cytokine-like functions, which are well known to orchestrate inflammatory responses within different organs. Overall, more than 50 ligands and 19 receptors belong to the network. In recent years, accumulating functional and genetic evidence suggests that chemokines play a critical role in acute and chronic liver diseases, mediating the infiltration of immune cells (monocytes, T-cells) into the injured liver along a concentration gradient. However, chemokines can also directly affect the biology of liver resident cells, such as hepatic stellate cells and hepatocytes during inflammatory and fibrogenic tissue responses. Although the chemokine system has long been cons... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083292 Tue, 20 Jul 2010 23:00:00 +0100 4083292 http://www.medworm.com/index.php?rid=4083291&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fdx.doi.org%2F10.1055%2Fs-0030-1255350 Semin Liver Dis 2010; 30: 211-214DOI: 10.1055/s-0030-1255350© Thieme Medical PublishersArticle in Thieme eJournals:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=4083291 Tue, 20 Jul 2010 23:00:00 +0100 4083291 http://www.medworm.com/index.php?rid=3506025&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1253523 We present a patient with an initial and acute presentation of jaundice and marked persistent pruritus. Laboratory and radiology test results eliminated the possibility of acute hepatitis A/B/C viral infections, primary biliary cirrhosis, autoimmune hepatitis, Wilson disease, paraneoplastic cholestasis, and obstructive biliary disease. Centrilobular cholestasis was prominent in a liver biopsy specimen. Benign recurrent intrahepatic cholestasis (BRIC) was diagnosed through a review of the clinical history, available data, and the subsequent exclusion of other possible etiologies. The patient's clinical features resolved within 3 months of medical treatment.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3506025 Tue, 27 Apr 2010 13:22:47 +0100 3506025 http://www.medworm.com/index.php?rid=3506024&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1253228 Semin Liver Dis 2010; 30: 195-204DOI: 10.1055/s-0030-1253228ABSTRACTCholestasis is a reduction in bile flow that occurs from a variety of causes in humans. This produces hepatocellular injury and fibrosis. Considering that there are limited therapies for this disease, there has been interest in understanding the mechanism by which cholestasis produces injury. Studies have demonstrated that oxidative stress occurs in livers of humans with cholestasis. In vitro studies have demonstrated that bile acids kill hepatocytes by a mechanism that depends upon reactive oxygen species (ROS). Further studies, however, have demonstrated that this mechanism is of limited importance in vivo. Cholestasis also initiates an inflammatory response resulting in accumulation of neutrophils in the liver. Inhibiti... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3506024 Tue, 27 Apr 2010 13:22:47 +0100 3506024 http://www.medworm.com/index.php?rid=3506023&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1253227 Semin Liver Dis 2010; 30: 186-194DOI: 10.1055/s-0030-1253227ABSTRACTHepatobiliary transport systems are essential for the uptake and excretion of a variety of compounds including bile acids. Disruption and dysregulation of this excretory pathway result in cholestasis, leading to the intrahepatic accumulation of bile acids and other toxic compounds with progression of liver pathology. Cholestasis induced by inflammation is a common complication in patients with extrahepatic infections or inflammatory processes, generally referred to as sepsis-associated cholestasis. Microbial products, including endotoxin, induce signaling pathways within hepatocytes either directly, or through activation of proinflammatory cytokines, leading to rapid and profound reductions in bile flow. The expression and... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3506023 Tue, 27 Apr 2010 13:22:47 +0100 3506023 http://www.medworm.com/index.php?rid=3506022&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1253226 Semin Liver Dis 2010; 30: 178-185DOI: 10.1055/s-0030-1253226ABSTRACTOrganic solute transporter alpha-beta (OSTα-OSTβ) is a unique heteromeric transporter localized to the basolateral membrane of epithelial cells involved in sterol transport. It is believed to be the primary bile acid efflux transporter in the intestine of mammals and is therefore essential to bile acid homeostasis and the enterohepatic circulation. First described in the evolutionarily primitive small skate, , this facilitated transporter requires expression of both subunits for its function. It can transport a variety of bile acids, as well as estrone 3-sulfate, dehydroepiandrosterone 3-sulfate, digoxin, and prostaglandin E. Expression of both subunits is variable between species and tissues; in humans high expr... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3506022 Tue, 27 Apr 2010 13:22:47 +0100 3506022 http://www.medworm.com/index.php?rid=3506021&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1253225 Semin Liver Dis 2010; 30: 160-177DOI: 10.1055/s-0030-1253225ABSTRACTAlthough hereditary or acquired defects in hepatobiliary transporter systems cause or predispose to cholestasis, adaptive bile acid transporter changes can counteract cholestasis by reducing hepatocellular and systemic concentrations of retained cholephiles. An important level in the regulation of adaptive bile acid transporters and overflow pathways is mediated at the transcriptional level by nuclear hormone receptors. Moreover, therapeutic approaches targeting nuclear receptors in cholestasis may stimulate these adaptive changes and open a new perspective for the treatment of cholestatic liver diseases. This review gives a comprehensive overview on bile acid transporters in the enterohepatic circulation and their adaptiv... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3506021 Tue, 27 Apr 2010 13:22:47 +0100 3506021 http://www.medworm.com/index.php?rid=3506020&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1253224 Semin Liver Dis 2010; 30: 147-159DOI: 10.1055/s-0030-1253224ABSTRACTIntrahepatic cholestasis of pregnancy and drug-induced cholestasis are two clinically important forms of acquired cholestatic liver disease. The understanding of the underlying mechanisms of acquired cholestasis has recently made considerable progress by the identification of canalicular ATP-binding cassette (ABC) transporters as likely targets for these forms of cholestasis. Cholestasis of pregnancy is linked to estrogen and progesterone metabolites. These metabolites have been shown to impair the bile salt export pump (BSEP) function by an indirect mechanism. In addition, genetic variants (as well as mutants) of the genes coding for the phosphatidylcholine translocator MDR3 and BSEP and for the farnesoid X receptor, whic... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3506020 Tue, 27 Apr 2010 13:22:47 +0100 3506020 http://www.medworm.com/index.php?rid=3506019&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1253223 Semin Liver Dis 2010; 30: 134-146DOI: 10.1055/s-0030-1253223ABSTRACTClass III multidrug resistance P-glycoproteins, Mdr2 in mice and MDR3 in human, are canalicular phospholipid translocators involved in biliary phospholipid (phosphatidylcholine) excretion. The role of an gene defect in liver disease has been initially proven in a subtype of progressive familial intrahepatic cholestasis called PFIC3, a severe pediatric liver disease that may require liver transplantation. Several mutations have been identified in children with PFIC3 and are associated with low level of phospholipids in bile leading to a high biliary cholesterol saturation index. mutations are associated with loss of canalicular MDR3 protein and /or loss of protein function. There is evidence that a biallelic or monoallelic ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3506019 Tue, 27 Apr 2010 13:22:47 +0100 3506019 http://www.medworm.com/index.php?rid=3506018&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1253222 Semin Liver Dis 2010; 30: 125-133DOI: 10.1055/s-0030-1253222ABSTRACTThe primary transporter responsible for bile salt secretion is the bile salt export pump (BSEP, ABCB11), a member of the ATP-binding cassette (ABC) superfamily, which is located at the bile canalicular apical domain of hepatocytes. In humans, deficiency results in several different genetic forms of cholestasis, which include progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2), as well as other acquired forms of cholestasis such as drug-induced cholestasis (DIC) and intrahepatic cholestasis of pregnancy (ICP). Because bile salts play a pivotal role in a wide range of physiologic and pathophysiologic processes, regulation of BSEP expression has been a subject... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3506018 Tue, 27 Apr 2010 13:22:47 +0100 3506018 http://www.medworm.com/index.php?rid=3506017&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1253221 Semin Liver Dis 2010; 30: 117-124DOI: 10.1055/s-0030-1253221ABSTRACTProgressive familial intrahepatic cholestasis type 1 is a rare genetic liver disease that presents in the first year of life. Bile salts are elevated and these patients are often jaundiced. Despite the cholestasis, serum gamma-glutamyltransferase activity is normal or reduced. Pruritus is a major symptom in these patients. Partial external biliary diversion is helpful in several patients as it reduces the pruritus and postpones or even avoids liver transplantation. The disease is caused by mutations in the gene that preclude the normal expression of . ATP8B1 is a protein that acts as a lipid flippase, transporting phosphatidylserine from the exoplasmic to the cytoplasmic leaflet of the canalicular membrane of hepatocytes. ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3506017 Tue, 27 Apr 2010 13:22:47 +0100 3506017 http://www.medworm.com/index.php?rid=3506016&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1253220 Semin Liver Dis 2010; 30: 113-115DOI: 10.1055/s-0030-1253220© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3506016 Tue, 27 Apr 2010 05:08:31 +0100 3506016 http://www.medworm.com/index.php?rid=3289390&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1247137 Semin Liver Dis 2010; 30: 107-112DOI: 10.1055/s-0030-1247137ABSTRACTThe authors present the case of a 48-year-old man with hepatitis B cirrhosis, who developed two primary malignant liver tumors that were morphologically distinct from each other. The first tumor was a hepatocellular carcinoma and the second tumor, detected 17 months later was a hepatic carcinosarcoma with cholangiocarcinomatous and sarcomatous components, without any hepatocellular carcinoma component. Clonality studies using microsatellite-based loss of heterozygosity (LOH) demonstrated different LOH patterns existed between the hepatocellular carcinoma and the hepatic carcinosarcoma, indicative of different clonal origins. The authors discuss the histogenesis, histopathologic diagnosis, and clinical behavior of hepatic c... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3289390 Sat, 20 Feb 2010 14:23:38 +0100 3289390 http://www.medworm.com/index.php?rid=3289389&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1247136 Semin Liver Dis 2010; 30: 099-106DOI: 10.1055/s-0030-1247136ABSTRACTThe incidence of hepatocellular carcinoma (HCC) is growing dramatically in the Western world. It is currently the fifth most common cancer worldwide, and the third most common cause of death from cancer. Studies clearly demonstrate that surveillance programs can increase the proportion of HCCs that are detected at an early stage, and improved therapeutic modalities, applied to early stage HCCs, improve cure rates and duration of survival in noncurable cases. What constitutes appropriate surveillance remains an unresolved issue. Measurements of serum α-fetoprotein and imaging, especially with ultrasound, are the most widely used elements in surveillance programs. The authors present a 70-year-old woman with chronic hep... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3289389 Sat, 20 Feb 2010 14:23:38 +0100 3289389 http://www.medworm.com/index.php?rid=3289388&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1247135 Semin Liver Dis 2010; 30: 087-098DOI: 10.1055/s-0030-1247135ABSTRACTThe etiology of liver cancer is well known, but despite recent progress in the application of molecular techniques for the analysis of the development of these tumors, we still lack precise knowledge about pathogenesis of hepatocellular carcinoma (HCC). Animal models can provide essential knowledge about HCC pathogenesis, particularly if they mimic the tissue environment in which human tumors develop. The synergism between studies in animal models and human tumors is strengthened by using comparative genomic analysis to identify genes and pathways that are critical for both mouse and human oncogenesis. In this article, the authors discuss some selective examples of constitutive, conditional, and inducible models of HCC dev... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3289388 Sat, 20 Feb 2010 14:23:38 +0100 3289388 http://www.medworm.com/index.php?rid=3289387&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1247134 Semin Liver Dis 2010; 30: 075-086DOI: 10.1055/s-0030-1247134ABSTRACTIdentification of novel oncogenes and tumor suppressors in hepatocellular carcinoma (HCC) is challenging, both because of the tumor complexity and the difficulty in integrating the very large amount of data provided by different approaches. The authors consider it very important to identify new pathways of carcinogenesis and to understand the mechanisms underlying their alteration in tumors to design personalized treatments for HCC. In this review, the main global genomic approaches are considered in detail. The authors present a catalog of the most important oncogenes and tumor suppressor genes that have been found to be mutated in HCC and hepatocellular adenoma. They also review the results provided by transcriptome and ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3289387 Sat, 20 Feb 2010 14:23:38 +0100 3289387 http://www.medworm.com/index.php?rid=3289386&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1247133 Semin Liver Dis 2010; 30: 061-074DOI: 10.1055/s-0030-1247133ABSTRACTStaging and treatment indication are relevant topics in the management of patients with hepatocellular carcinoma (HCC) and for optimal results, they have to take into account liver function, tumor stage, and physical status. For any staging system to be meaningful it has to link staging with treatment indication; this should be based on robust scientific data. Currently, the sole proposal that serves both aims is the Barcelona Clinic Liver Cancer (BCLC) approach. It takes into account the relevant parameters of all important dimensions and divides patients into very early/early, intermediate, advanced, and end-stage. Early-stage HCC patients should be considered for potentially curative options such as resection, ablation,... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3289386 Sat, 20 Feb 2010 14:23:38 +0100 3289386 http://www.medworm.com/index.php?rid=3289385&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1247132 Semin Liver Dis 2010; 30: 052-060DOI: 10.1055/s-0030-1247132ABSTRACTThe endpoint in cancer research is overall survival. Nonetheless, other potential surrogate endpoints, such as response rate and time to progression, are currently used. Measurement of response rate in hepatocellular carcinoma (HCC) has become a controversial issue. The World Health Organization (WHO) criteria underestimate the actual response rate; thus, they were amended in 2000 by a panel of experts convened by the European Association for the Study of the Liver (EASL) to take into account treatment-induced tumor necrosis. Applying these guidelines, there was an association between response rate and outcome prediction. More recently, the Response Evaluation Criteria in Solid Tumors (RECIST) guideline was proposed as a m... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3289385 Sat, 20 Feb 2010 14:23:38 +0100 3289385 http://www.medworm.com/index.php?rid=3289384&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1247131 Semin Liver Dis 2010; 30: 035-051DOI: 10.1055/s-0030-1247131ABSTRACTHepatocellular carcinoma (HCC) is one of most lethal cancers worldwide. Strategic decisions for the advancement of molecular therapies in this neoplasm require a clear understanding of its molecular classification. Studies indicate aberrant activation of signaling pathways involved in cellular proliferation (e.g., epidermal growth factor and RAS/mitogen-activated protein kinase pathways), survival (e.g., Akt/mechanistic target of rapamycin pathway), differentiation (e.g., Wnt and Hedgehog pathways), and angiogenesis (e.g., vascular endothelial growth factor and platelet-derived growth factor), which is heterogeneously presented in each tumor. Integrative analysis of accumulated genomic datasets has revealed a global scheme... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3289384 Sat, 20 Feb 2010 14:23:38 +0100 3289384 http://www.medworm.com/index.php?rid=3289383&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1247130 Semin Liver Dis 2010; 30: 026-034DOI: 10.1055/s-0030-1247130ABSTRACTIncreasing evidence suggests that many, perhaps all solid tumors contain a subset of cells that possess functional properties similar to the normal tissue stem cells, including self-renewal, unlimited proliferative capacity, and pluripotency. The hierarchical cancer model that places a cancer stem cell (CSC) population at the apex of tumor formation is based on this notion. The cancer stem cell hypothesis posits that CSCs are responsible not only for tumor initiation, but also generation of metastasis and local recurrence after therapy. Current definitions of the CSC are based only on functional properties regardless of potential cellular origin. Histopathology investigations of chronic liver diseases and experimental stud... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3289383 Sat, 20 Feb 2010 14:23:38 +0100 3289383 http://www.medworm.com/index.php?rid=3289382&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1247129 Semin Liver Dis 2010; 30: 017-025DOI: 10.1055/s-0030-1247129ABSTRACTRecently, an East–West consensus on the histopathologic criteria for the diagnosis of high-grade dysplastic nodules (HGDN) versus early hepatocellular carcinoma (HCC) was reached. Next to classical morphologic criteria such as nucleocytoplasmic ratio, thickness of cell plates, mitotic index, and architectural disturbance like acinar structures, one of the most relevant criteria to diagnose early HCC is stromal invasion. Because a structured basement membrane is lacking along the hepatocytes in the liver, invasion cannot be defined as tumor growth through the basement membrane as in other tissues. However, the number of portal tracts that are present in a nodule gradually decrease because the tumoral hepatocytes start... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3289382 Sat, 20 Feb 2010 14:23:38 +0100 3289382 http://www.medworm.com/index.php?rid=3289381&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1247128 Semin Liver Dis 2010; 30: 003-016DOI: 10.1055/s-0030-1247128ABSTRACTHepatocellular carcinoma (HCC) is increasing in incidence in many countries, and is the most common cause of death in patients with cirrhosis. With regular surveillance, small early HCC lesions can be identified. An algorithm has been developed that allows for diagnosis of these lesions. Very early HCC lesions have high cure rates with appropriate treatment. If all these factors are in place most HCCs can be cured.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3289381 Sat, 20 Feb 2010 14:23:38 +0100 3289381 http://www.medworm.com/index.php?rid=3289380&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0030-1247219 Semin Liver Dis 2010; 30: 001-002DOI: 10.1055/s-0030-1247219© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=3289380 Sat, 20 Feb 2010 03:24:17 +0100 3289380 http://www.medworm.com/index.php?rid=2888145&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240011 Semin Liver Dis 2009; 29: 423-428DOI: 10.1055/s-0029-1240011ABSTRACTNonalcoholic steatosis/steatohepatitis is the most common cause for abnormal liver chemistries. Apart from metabolic syndrome, drugs may also lead to development of steatohepatitis that may, rarely, progress to cirrhosis and portal hypertension. We discuss a case of amiodarone-induced steatohepatitis with advanced fibrosis, presenting with hepatic decompensation and portal hypertension manifesting as ascites and recurrent esophageal variceal hemorrhage. Amiodarone is a lipophilic drug that concentrates in the liver and usually, over a period of time, leads to toxicity related to drug accumulation. There is marked histological similarity between amiodarone-induced liver disease and alcoholic and nonalcoholic steatohepatitis... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2888145 Wed, 14 Oct 2009 13:12:58 +0100 2888145 http://www.medworm.com/index.php?rid=2888144&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240010 Semin Liver Dis 2009; 29: 412-422DOI: 10.1055/s-0029-1240010ABSTRACTThe “statins,” or hydroxymethylglutaryl coenzyme A (HMG-CoA)-reductase inhibitors, are a generally safe class of drugs that are widely used throughout the world and are rarely associated with severe hepatotoxicity. In this article, two cases of severe hepatotoxicity attributed to statin use are presented. In addition, a detailed summary of previously published cases of statin hepatotoxicity and the risks and benefits of statins in patients with chronic liver disease are presented. Drug-induced liver injury (DILI) from statins typically presents with an acute hepatocellular liver injury pattern, although mixed or cholestatic injury patterns have also been reported. Nonspecific autoantibodies as well as clinical,... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2888144 Wed, 14 Oct 2009 13:12:58 +0100 2888144 http://www.medworm.com/index.php?rid=2888143&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240009 Semin Liver Dis 2009; 29: 400-411DOI: 10.1055/s-0029-1240009ABSTRACTGenetic studies on drug-induced liver injury (DILI) have proved challenging, both because of their rarity and their difficulty in replicating observed effects. However, significant progress has now been achieved by both candidate-gene and genome-wide association studies. These two approaches are considered in detail, together with examples of DILI due to specific drugs where consistent associations have been reported. Particular consideration is given to associations between antituberculosis drug-related liver injury and the “slow acetylator” genotype for -acetyltransferase 2, amoxicillin/clavulanate-related liver injury, and the human leukocyte antigen (HLA) class II allele and flucloxacillin-related injury an... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2888143 Wed, 14 Oct 2009 13:12:58 +0100 2888143 http://www.medworm.com/index.php?rid=2888142&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240008 Semin Liver Dis 2009; 29: 393-399DOI: 10.1055/s-0029-1240008ABSTRACTThere is a pressing need for new clinical tests that will help physicians distinguish drug-induced liver injury (DILI) from other, more common causes of liver injury, and that can identify which specific drug is the culprit when DILI occurs in the setting of polypharmacy. In situations where there are few alternative treatments, new tests are needed that can differentiate patients with DILI who would develop progressive liver injury if treatment is not stopped from patients who can safely continue drug therapy via “adaptation.” Although there has been little progress in developing and validating such tests, new insights into the mechanisms underlying DILI suggest that the desired biomarkers probably exist and c... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2888142 Wed, 14 Oct 2009 13:12:58 +0100 2888142 http://www.medworm.com/index.php?rid=2888141&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240007 Semin Liver Dis 2009; 29: 383-392DOI: 10.1055/s-0029-1240007ABSTRACTNo conclusive data exist that define the mechanisms of idiosyncratic drug-induced liver injury (DILI) in humans; therefore, we are forced to speculate based on their clinical characteristics. The major characteristics are most easily explained by an immune mechanism. Many cases of idiosyncratic DILI tend to have a longer delay in onset and sometimes do not occur rapidly on rechallenge. These instances of DILI have been attributed to metabolic idiosyncrasy. However, these characteristics may also reflect an autoimmune mechanism, and most drugs that cause idiosyncratic DILI are also associated with various types of other autoimmune reactions. A characteristic feature of the immune system is that different individuals respond... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2888141 Wed, 14 Oct 2009 13:12:58 +0100 2888141 http://www.medworm.com/index.php?rid=2888140&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240006 Semin Liver Dis 2009; 29: 373-382DOI: 10.1055/s-0029-1240006ABSTRACTHerbal and dietary supplements (HDS) are commonly used in the United States and throughout the world. The Dietary Supplement Health and Education Act and public standards set through the U.S. Pharmacopeia provide regulatory framework for these products. These regulations help to ensure the safety of grandfathered and new HDS coming onto the market, and the opportunity to identify and take action against unsafe products that have been distributed. The clinical patterns of presentation and severity of HDS-associated hepatotoxicity can be highly variable, even for the same product. In addition, accurate causality assessment in cases of suspected HDS hepatotoxicity is confounded by infrequent ascertainment of product intake by... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2888140 Wed, 14 Oct 2009 13:12:58 +0100 2888140 http://www.medworm.com/index.php?rid=2888139&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240005 This article outlines a practical approach to the diagnosis of DILI on liver biopsy, including the common patterns of injury observed in drug- and toxin-induced liver pathology and prognostic pathological features that may be associated with the outcome of patients with DILI.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2888139 Wed, 14 Oct 2009 13:12:58 +0100 2888139 http://www.medworm.com/index.php?rid=2888138&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240004 Semin Liver Dis 2009; 29: 357-363DOI: 10.1055/s-0029-1240004ABSTRACTThe development of acute hepatocellular injury with jaundice in patients with drug-induced liver injury (DILI) has been associated with a case-fatality rate of 10 to 50%, depending on the drug involved. This observation, called “Hy's rule,” is frequently used by regulatory agencies in assessing the hepatotoxic potential of drugs being tested in clinical trials. Registry studies from Sweden, Spain, and the United States have confirmed the validity of Hy's rule by demonstrating a 9 to 12% mortality rate in consecutive DILI patients. In patients with suspected DILI, the causative agent should be immediately discontinued, and hospitalized patients with severe coagulopathy or encephalopathy should be referred for po... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2888138 Wed, 14 Oct 2009 13:12:58 +0100 2888138 http://www.medworm.com/index.php?rid=2888137&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240003 Semin Liver Dis 2009; 29: 348-356DOI: 10.1055/s-0029-1240003ABSTRACTAssigning causality in drug-induced liver injury (DILI) due to a particular medication or herbal and dietary supplement relies on clinical history, exclusion of competing causes, prior reports of DILI, and judgment—no objective laboratory or histological tests exist to confirm a diagnosis of suspected DILI. Current causality assessment instruments are based on algorithmic scoring systems but are not widely used. Expert opinion remains the gold standard, but is cumbersome and has limited reproducibility. The lack of a valid and widely available causality assessment method hinders the identification of genetic and biochemical markers that may help better define DILI. Emerging technologies in pharmacogenomics and toxico... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2888137 Wed, 14 Oct 2009 13:12:58 +0100 2888137 http://www.medworm.com/index.php?rid=2888136&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240002 Semin Liver Dis 2009; 29: 337-347DOI: 10.1055/s-0029-1240002ABSTRACTIdiosyncratic drug-induced liver injury (DILI) is a significant health problem because of its unpredictable nature, poorly understood pathogenesis, and potential to cause fatal outcomes. It is also a significant hurdle for drug development and marketing of safe prescription medications. Idiosyncratic DILI is generally rare, but its occurrence is likely underappreciated due to the lack of active reporting or surveillance systems and substantial challenges involved in its recognition and diagnosis. Nonetheless, DILI is a common cause of potentially serious and fatal acute liver failure in both children and adults. Population-based studies that accurately estimate the incidence and full spectrum of DILI are limited. However, ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2888136 Wed, 14 Oct 2009 13:12:58 +0100 2888136 http://www.medworm.com/index.php?rid=2888135&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1240001 Semin Liver Dis 2009; 29: 335-336DOI: 10.1055/s-0029-1240001© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2888135 Wed, 14 Oct 2009 00:47:35 +0100 2888135 http://www.medworm.com/index.php?rid=2693347&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1233537 Semin Liver Dis 2009; 29: 331-334DOI: 10.1055/s-0029-1233537ABSTRACTThe pathogenesis of autoimmune hepatitis entails complex interactions between triggering factors, autoantigens, genetic predisposition, and immunoregulatory networks. Implicated triggering factors are numerous and include toxins, medications, and infectious agents. In this article, we present a unique case of a 31-year-old woman with severe autoimmune hepatitis apparently abruptly triggered by vaccination. All evidence suggests this was an idiosyncratic response to either hepatitis A or yellow fever vaccination.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2693347 Thu, 13 Aug 2009 10:53:53 +0100 2693347 http://www.medworm.com/index.php?rid=2693346&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1233530 The objectives of this report are to characterize the populations that are underdiagnosed or difficult to manage and to provide guidelines for meeting their challenges. The elderly have an aggressive, indolent liver disease that responds well to conventional corticosteroid treatment, but the diagnosis of this disease can be hampered by concurrent illnesses and medication. Genetic factors affect the expression and outcome of autoimmune hepatitis in different genders, and they may influence the nature and reactivity to triggering antigens or hormonal imbalances. Pregnancy can ameliorate autoimmune hepatitis, whereas delivery can exacerbate it. Asymptomatic patients and those with mild laboratory derangements may not require immediate therapy, but they commonly require treatment later. Centri... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2693346 Thu, 13 Aug 2009 10:53:53 +0100 2693346 http://www.medworm.com/index.php?rid=2693345&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1233535 Semin Liver Dis 2009; 29: 307-314DOI: 10.1055/s-0029-1233535ABSTRACTAutoimmune polyglandular syndromes are rare autoimmune endocrinopathies that are associated with nonendocrine autoimmunopathies. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also named autoimmune polyglandular syndrome type 1 (APS-1), is distinguished from autoimmune polyglandular syndrome 2 (APS-2). Major disease components of APECED are adrenal insufficiency, hypoparathyroidism, and candidiasis. The diagnosis is established by the presence of two out of the three components. Minor clinical features include autoimmune hepatitis, which occurs in up to 20% of APECED patients, and ranges from a mild to a fulminant course. The disease mostly affects juvenile patients from Sardegna, Italy, Finland, ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2693345 Thu, 13 Aug 2009 10:53:53 +0100 2693345 http://www.medworm.com/index.php?rid=2693344&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1233529 Semin Liver Dis 2009; 29: 297-306DOI: 10.1055/s-0029-1233529ABSTRACTAutoimmune hepatitis (AIH) is characterized by inflammatory liver histology, circulating non-organ-specific autoantibodies, and increased levels of immunoglobulin (Ig) G in the absence of a known etiology. Two types of childhood AIH are recognized according to seropositivity: smooth muscle antibody (SMA) and/or antinuclear antibody (ANA), which is AIH type 1; and antibodies to liver-kidney microsome type 1 (anti-LKM1), which is AIH type 2. There is a female predominance in both. Autoimmune hepatitis type 2 presents more acutely, at a younger age, and commonly with IgA deficiency; however, duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, resp... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2693344 Thu, 13 Aug 2009 10:53:53 +0100 2693344 http://www.medworm.com/index.php?rid=2693343&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1233531 Semin Liver Dis 2009; 29: 286-296DOI: 10.1055/s-0029-1233531ABSTRACTFor those with autoimmune hepatitis (AIH), indications for liver transplantation include end-stage liver failure (as suggested by a MELD score >16), the onset of liver cancer, intractable symptoms that make the patient's life intolerable, and fulminant liver failure; outcomes are excellent, with 10-year survival in excess of 70%. For those with a fulminant presentation, the impact of corticosteroids is controversial and liver transplantation may be required. Autoimmune hepatitis recurs in approximately one third and may be detected up to 10 years or more post-transplant. There are no agreed-on criteria for the diagnosis, and differentiation from rejection and other causes of graft damage can be difficult. There is no st... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2693343 Thu, 13 Aug 2009 10:53:53 +0100 2693343 http://www.medworm.com/index.php?rid=2693342&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1233534 Semin Liver Dis 2009; 29: 273-285DOI: 10.1055/s-0029-1233534ABSTRACTFirst described in 1950, autoimmune hepatitis (AIH) was the first chronic liver disease with a favorable response to drug therapy and a dismal prognosis when left untreated. In the decades since the first treatment studies, the basic strategic principle of inducing remission with steroids and azathioprine has not been modified. The main problems are a timely diagnosis before cirrhosis develops, the avoidance of immunosuppressant side effects, nonresponders to standard induction therapy, and adherence to therapy. Alternative drugs for immunosuppression have been tested in small series and include transplant immunosuppressants. A large multicenter prospective treatment trial suggests that budesonide may offer an alternative ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2693342 Thu, 13 Aug 2009 10:53:53 +0100 2693342 http://www.medworm.com/index.php?rid=2693341&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1233536 Semin Liver Dis 2009; 29: 262-272DOI: 10.1055/s-0029-1233536ABSTRACTAutoimmune hepatitis (AIH) is often diagnosed late in the disease course and usually requires lifelong immunosuppressive therapy. Unfortunately, the etiology of the disease and the mechanisms leading to the autoimmune destruction of the liver parenchyma are only poorly understood. For a long time, one reason for this lack of apprehension was the absence of reliable animal models with a chronic immune response against liver tissues. Initial attempts to break tolerance against hepatocytes usually just resulted in mild, transient hepatitis flares. Recently, however, some approaches have been made to establish models of chronic AIH that reflect the immunopathogenic mechanisms seen in humans. In this article, we reflect on rece... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2693341 Thu, 13 Aug 2009 10:53:53 +0100 2693341 http://www.medworm.com/index.php?rid=2693340&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1233532 Semin Liver Dis 2009; 29: 254-261DOI: 10.1055/s-0029-1233532ABSTRACTThe diagnosis of autoimmune hepatitis (AIH) can be challenging due to the variable clinical and laboratory findings. The original diagnostic criteria published in 1993 by the International Autoimmune Hepatitis Group (IAIHG) were revised in 1999 in an attempt to standardize the diagnosis. However, these criteria are complex and can be cumbersome in clinical practice. In 2008, simplified diagnostic criteria were reported to facilitate the bedside diagnosis of AIH. The scoring systems have been evaluated in several retrospective case series and tested for their ability to reliably diagnose and exclude AIH. However, the scoring systems did not fare as well in patients with concomitant cholestatic disease, fatty liver disease, ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2693340 Thu, 13 Aug 2009 10:53:53 +0100 2693340 http://www.medworm.com/index.php?rid=2693339&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1233533 This article critically discusses the current knowledge of the diagnostic and clinical significance of AIH-related autoantibody reactivities, focusing on key issues that the physician needs to be aware of to be able to request the appropriate testing and to interpret correctly the laboratory results within the clinical context of the patient.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2693339 Thu, 13 Aug 2009 10:53:53 +0100 2693339 http://www.medworm.com/index.php?rid=2693338&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1233528 Semin Liver Dis 2009; 29: 239-240DOI: 10.1055/s-0029-1233528© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2693338 Thu, 13 Aug 2009 10:53:53 +0100 2693338 http://www.medworm.com/index.php?rid=2357973&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1216299 We present the case of a patient with hepatitis B virus infection and alcohol use (30 g/day by self-report) who developed cirrhosis and proceeded to liver transplantation at age 49. The explanted liver showed cirrhosis with evidence of burnt-out steatohepatitis and hepatitis B virus and a 0.7-cm focus of well-differentiated hepatocellular carcinoma. He was managed following transplant with tacrolimus, prednisone, lamivudine, adefovir, and hepatitis B immune globulin infusions. His post-transplant course was complicated by several episodes of elevated liver enzymes. Liver biopsy 3 months after liver transplantation showed acute rejection and mild steatohepatitis. Liver biopsy 6 months after liver transplantation showed marked steatosis (~95%) with moderate steatohepatitis and evidence of tr... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2357973 Thu, 23 Apr 2009 01:31:18 +0100 2357973 http://www.medworm.com/index.php?rid=2357966&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214377 Semin Liver Dis 2009; 29: 222-232DOI: 10.1055/s-0029-1214377ABSTRACTHepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and contributes significantly to cancer-related morbidity and mortality. Chronic alcohol consumption has long been associated with progressive liver disease toward the development of hepatic cirrhosis and the subsequent increased risk for developing HCC. In assessing the role of alcohol during hepatic disease, and as a carcinogen, many of the deleterious effects of alcohol can be attributed to alcohol metabolism in hepatocytes. In addition to the direct effects of alcohol/alcohol metabolism on hepatocyte transformation, increasing evidence indicates that other intrahepatic and systemic effects of alcohol are likely to play an equally sig... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2357966 Thu, 23 Apr 2009 01:31:17 +0100 2357966 http://www.medworm.com/index.php?rid=2357959&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214376 Semin Liver Dis 2009; 29: 211-221DOI: 10.1055/s-0029-1214376ABSTRACTAlcoholic liver disease involves significant crosstalk among intracellular signaling events in the liver. Overall, inflammatory and innate immune responses in Kupffer cells due to elevated gut-derived plasma endotoxin levels, increased reactive oxygen species-induced damage, and profibrogenic factors such as acetaldehyde or lipid peroxidation products contribute to activation of hepatic stellate cells, the key cell type involved in liver fibrosis. Using in vitro and in vivo approaches, there has been great progress in our understanding of the mechanisms leading to liver fibrosis: potential biomarkers of fibrosis have been identified, and several candidate targets for antifibrotic drugs have been elucidated.[...]© Thieme M... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2357959 Thu, 23 Apr 2009 01:31:17 +0100 2357959 http://www.medworm.com/index.php?rid=2357951&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214375 Semin Liver Dis 2009; 29: 200-210DOI: 10.1055/s-0029-1214375ABSTRACTSubpopulations of individuals with alcohol-induced fatty livers and nonalcoholic steatosis develop steatohepatitis. Steatohepatitis is defined histologically: increased numbers of injured and dying hepatocytes distinguish this condition from simple steatosis. The increased hepatocyte death is generally accompanied by hepatic accumulation of inflammatory cells and sometimes increases in myofibroblastic cells, leading to hepatic fibrosis and eventually, cirrhosis. The purpose of this review is to summarize similarities and differences in the pathogenesis of steatohepatitis in alcoholic fatty liver disease and nonalcoholic fatty liver disease.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract �... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2357951 Thu, 23 Apr 2009 01:31:17 +0100 2357951 http://www.medworm.com/index.php?rid=2357943&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214374 Semin Liver Dis 2009; 29: 188-199DOI: 10.1055/s-0029-1214374ABSTRACTThis review will focus on the prevalence of hepatitis c virus (HCV) infection in alcoholics with and without liver disease. Evidence will be presented to demonstrate that ethanol and chronic HCV infection synergistically accelerate liver injury. Some of the major postulated mechanisms responsible for disease progression include high rates of apoptosis, lipid peroxidation, and generation of free radicals and reactive oxygen species with reduced antioxidant capacity of the liver. Acquisition and persistence of HCV infection may be due to the adverse effects of ethanol on humoral and cellular immune responses to HCV. Dendritic cells (DC) appear to be one of the major targets for ethanol's action and DC dysfunction impairs the... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2357943 Thu, 23 Apr 2009 01:31:17 +0100 2357943 http://www.medworm.com/index.php?rid=2357935&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214373 Semin Liver Dis 2009; 29: 178-187DOI: 10.1055/s-0029-1214373ABSTRACTAlcoholic liver disease (ALD) is a lifestyle disease with its pathogenesis and individual predisposition governed by gene–environment interactions. Based on the “second hit” or “multiple hits” hypothesis, patients are predisposed to progressive ALD when a magic combination of gene and environmental interactions exists. Reproduction of second or multiple hits in animal models serves to test a combination and to gain mechanistic insights into synergism achieved by such combination. Numerous environmental factors have been incorporated into animal models, largely classified into nutritional, xenobiotic/pharmacologic, hemodynamic, and viral groups. A loss or gain of function genetic model has beco... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2357935 Thu, 23 Apr 2009 01:31:17 +0100 2357935 http://www.medworm.com/index.php?rid=2357928&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214372 Semin Liver Dis 2009; 29: 166-177DOI: 10.1055/s-0029-1214372ABSTRACTAlcoholic liver injury involves a complex array of derangements in cellular signaling of hepatic parenchymal and nonparenchymal cells as well as cells of the immune system. In the hepatocyte, chronic ethanol abuse leads to lipid accumulation and liver steatosis. Multiple pathways are affected to promote lipid accumulation in the ethanol-exposed hepatocyte. Chronic ethanol renders Kupffer cells hyperresponsive to endotoxin, which results in production of inflammatory cytokines and the tumor necrosis factor-α via a toll-like receptor 4 dependent pathway, leading to inflammation and hepatic necrosis. Dysfunction of the innate and adaptive immune responses caused by ethanol contributes to impaired antiviral response, infl... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2357928 Thu, 23 Apr 2009 01:31:17 +0100 2357928 http://www.medworm.com/index.php?rid=2357920&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214371 Semin Liver Dis 2009; 29: 155-165DOI: 10.1055/s-0029-1214371ABSTRACTAlcoholic liver disease is a major health care problem worldwide. Findings have demonstrated that ethanol feeding impairs several of the multiple steps in methionine metabolism that leads to progressive liver injury. Ethanol consumption has been reported to predominantly inhibit the activity of a vital cellular enzyme, methionine synthase, involved in remethylating homocysteine. By way of compensation in some species, ethanol can also increase the activity of the enzyme, betaine homocysteine methyltransferase. This enzyme catalyzes an alternate pathway in methionine metabolism and utilizes hepatic betaine to remethylate homocysteine to form methionine and maintain levels of S-adenosylmethionine, the key methylating agent. ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2357920 Thu, 23 Apr 2009 01:31:17 +0100 2357920 http://www.medworm.com/index.php?rid=2357911&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214370 Semin Liver Dis 2009; 29: 141-154DOI: 10.1055/s-0029-1214370ABSTRACTReactive oxygen species (ROS) are highly reactive molecules that are naturally generated in small amounts during the body's metabolic reactions and can react with and damage complex cellular molecules such as lipids, proteins, or DNA. This review describes pathways involved in ROS formation, why ROS are toxic to cells, and how the liver protects itself against ROS. Acute and chronic ethanol treatment increases the production of ROS, lowers cellular antioxidant levels, and enhances oxidative stress in many tissues, especially the liver. Ethanol-induced oxidative stress plays a major role in the mechanisms by which ethanol produces liver injury. Many pathways play a key role in how ethanol induces oxidative stress. This revi... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2357911 Thu, 23 Apr 2009 01:31:17 +0100 2357911 http://www.medworm.com/index.php?rid=2357902&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1214369 Semin Liver Dis 2009; 29: 139-139DOI: 10.1055/s-0029-1214369© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2357902 Thu, 23 Apr 2009 00:47:04 +0100 2357902 http://www.medworm.com/index.php?rid=2211200&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1202551 Semin Liver Dis 2009; 29: 134-138DOI: 10.1055/s-0029-1202551ABSTRACTA 15-year-old boy who underwent liver transplantation for fulminant Wilson's disease, presented with elevated transaminases 2 months post-transplant. He had recently seroconverted from previous Epstein-Barr virus (EBV) naive status and by polymerase chain reaction (PCR) had increasing viral load copies of EBV in blood. A liver biopsy was obtained 6 weeks post-transplant, which showed isolated central perivenulitis (CP). His immunosuppresion was reduced and antiviral therapy was added with subsequent increase in liver transaminases. A second liver biopsy 6 weeks later again showed isolated CP. Subsequent further reduction in immunosuppression was followed by the appearance of portal-based moderate acute cellular rejection t... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2211200 Wed, 25 Feb 2009 03:46:51 +0100 2211200 http://www.medworm.com/index.php?rid=2211199&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1192060 Semin Liver Dis 2009; 29: 121-133DOI: 10.1055/s-0029-1192060ABSTRACTThe growing discrepancy between the need and the availability of donor livers has resulted in evolving surgical approaches in liver transplantation during the last two decades to expand the donor pool. One approach is to transplant partial grafts, obtained either from a living donor or splitting a cadaveric donor liver. For both surgical methods, it is important to obtain a minimal viable graft volume to prevent small-for-size syndrome and graft failure. This minimal volume, expressed as graft-to-whole body ratio, must be between 0.8 and 1%. Living donor liver transplantation (LDLT) became the primary transplant option in many Asian countries and is increasingly performed as an adjunct transplant option in countries with l... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2211199 Wed, 25 Feb 2009 03:46:51 +0100 2211199 http://www.medworm.com/index.php?rid=2211198&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1192059 Semin Liver Dis 2009; 29: 102-120DOI: 10.1055/s-0029-1192059ABSTRACTAs outcomes after liver transplant surgery continue to improve, management of the long-term consequences of the procedure and the associated immunosuppression become increasingly important. Liver allograft recipients have, compared with age and sex-matched controls, increased risk for cardiovascular and cerebrovascular events and death, for bone disease, and for some cancers. Early recognition and treatment of modifiable risk factors, especially of hypertension (present in up to 77% recipients), diabetes (in up to 22%), obesity (up to 40%), renal impairment (in up to 50%), and hyperlipidemia (in up to 66%) are necessary to maintain prolonged and healthy survival. Early recognition of de novo cancers (which occur in up to 2... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2211198 Wed, 25 Feb 2009 03:46:51 +0100 2211198 http://www.medworm.com/index.php?rid=2211197&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1192058 Semin Liver Dis 2009; 29: 091-101DOI: 10.1055/s-0029-1192058ABSTRACTSpontaneous acceptance of liver allografts occurs in several species. However, tolerance is rare in human transplant patients even though rejection is relatively easily reversed. Histological features of acute rejection in liver transplantation are similar to those in other organs. Nevertheless, mechanisms of rejection of liver transplants may differ in degrees and cellular involvement. Liver-specific cell populations, such as Kupffer cells (KCs), liver sinusoidal epithelial cells (LSECs), and hepatic stellate cells (HSCs), may contribute to liver tolerogenicity. Other mechanisms, such as microchimerism, soluble major histocompatibility complex (MHC molecules), donor human leukocyte antigen (HLA)-C genotype, and regulatory... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2211197 Wed, 25 Feb 2009 03:46:51 +0100 2211197 http://www.medworm.com/index.php?rid=2211196&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1192057 This article focuses on the main patterns of damage that are seen in liver allograft biopsies. As with the interpretation of liver biopsies from the native liver, clinicopathological correlation is very important. The therapeutic implications of the biopsy report should also be considered, in particular whether changes in immunosuppression are indicated. For some conditions, such as liver allograft rejection, histology remains the gold standard for diagnosis. In other cases, a likely cause of graft dysfunction may already have been identified by other methods, but liver biopsy still provides useful additional information (e.g., assessing disease severity in hepatitis C infection) and may identify an additional or alternative cause for graft dysfunction (e.g., coexistent metabolic fatty liv... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2211196 Wed, 25 Feb 2009 03:46:51 +0100 2211196 http://www.medworm.com/index.php?rid=2211195&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1192056 Semin Liver Dis 2009; 29: 066-073DOI: 10.1055/s-0029-1192056ABSTRACTAlcoholic liver disease is an important cause of cirrhosis, liver-associated death, and need for liver transplant. Up to 50% of recipients use some alcohol, and perhaps 10% drink addictively. Careful evaluation by an addiction medicine specialist is the best predictive instrument before transplant surgery, whereas the 6-month rule lacks sensitivity and specificity. Addictive drinking, but not minor slips, is associated with increased mortality. There is no standard therapy for alcoholism in alcoholics waiting for a transplant or for those who have undergone a transplant. Stably abstinent, methadone-maintained opiate-dependent patients should continue methadone; are generally good candidates for liver transplant; and show l... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2211195 Wed, 25 Feb 2009 03:46:51 +0100 2211195 http://www.medworm.com/index.php?rid=2211194&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1192055 Semin Liver Dis 2009; 29: 053-065DOI: 10.1055/s-0029-1192055ABSTRACTHepatitis C virus (HCV) is a leading cause of end-stage liver disease worldwide and the most common indication for liver transplantation in the United States and Europe. HCV nearly always recurs in liver-transplanted patients, and 10 to 25% of them develop cirrhosis within 5 to 10 years. One of the strategies suggested to limit virological HCV recurrence is pretransplant antiviral treatment, but studies are warranted on the pharmacokinetics of antiviral drugs in cirrhotic patients, the benefits of fixed or escalating antiviral drug dosage schedules, the duration of the treatment, and the indications for using growth factors. Several risk factors are associated with a more aggressive recurrent HCV and early allograft failur... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2211194 Wed, 25 Feb 2009 03:46:51 +0100 2211194 http://www.medworm.com/index.php?rid=2211193&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1192054 Semin Liver Dis 2009; 29: 040-052DOI: 10.1055/s-0029-1192054ABSTRACTOptimal candidate selection and organ allocation should offer liver transplantation to those who are sufficiently sick to justify the procedure but not too sick to benefit from it, in an order determined by patients' projected survival benefit, matching organs of sufficiently good quality to the appropriate recipients. Significant steps have been made in recent years toward devising selection and allocation criteria based on more objective and evidence-based definitions of candidate disease severity, transplant futility, organ quality, and appropriate donor-recipient matching. However, much work remains to be done in the future.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full t... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2211193 Wed, 25 Feb 2009 03:46:51 +0100 2211193 http://www.medworm.com/index.php?rid=2211192&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1192053 Semin Liver Dis 2009; 29: 019-039DOI: 10.1055/s-0029-1192053ABSTRACTLiver transplantation expertise has expanded throughout the world to the point where liver transplants are available in most developed countries. In many cases, however, legislation and regulations have not kept pace with the advances in healthcare technology. In a few cases, these regulatory voids have lead to exploitation and profit making around transplantation activities. The growing patient demand has motivated governments to develop numerous national efforts to improve the standards by which organ donation and transplantation are practiced and programs to increase the number organ of donors, most notably in Spain. Although these efforts have helped, the worldwide demand for lifesaving transplantation exerts extreme p... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2211192 Wed, 25 Feb 2009 03:46:51 +0100 2211192 http://www.medworm.com/index.php?rid=2211191&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1192052 This article discusses the utility of the mentioned techniques along with other strategies (e.g., Model for End-Sage Liver Disease [MELD] score), as well as the evolution of indications, contraindications, and postoperative care.[...]© Thieme Medical PublishersGet connected:Table of contents  |  Abstract  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2211191 Wed, 25 Feb 2009 03:46:51 +0100 2211191 http://www.medworm.com/index.php?rid=2211190&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0029-1192051 Semin Liver Dis 2009; 29: 001-001DOI: 10.1055/s-0029-1192051© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=2211190 Wed, 25 Feb 2009 03:46:51 +0100 2211190 http://www.medworm.com/index.php?rid=1911468&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1091987 Semin Liver Dis 2008; 28: 434-439DOI: 10.1055/s-0028-1091987ABSTRACTThe authors describe multiple telangiectatic or inflammatory adenomas in a 53-year-old woman with steatohepatitis who presented with acute right upper quadrant abdominal pain. Magnetic resonance imaging revealed 6 lesions consistent with multiple hepatic adenomas, 2 of which showed hemorrhage. She underwent right lobectomy and nonanatomical segment 2 liver resections and seven nodules ranging in size from 1.0 to 5.0 cm were identified. All nodules contained portal-like structures and ductular reaction, features seen in focal nodular hyperplasia, as well as significant inflammation, telangiectatic sinusoids and immunoreactivity for serum amyloid A, placing them according to a recently described classification systems as tel... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=1911468 Tue, 28 Oct 2008 12:30:15 +0100 1911468 http://www.medworm.com/index.php?rid=1911467&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1091986 Semin Liver Dis 2008; 28: 427-433DOI: 10.1055/s-0028-1091986ABSTRACTNonalcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases worldwide, affecting men, women, and children. This is due, in part, to the obesity epidemic, which is associated with increased prevalence of NAFLD. The NAFLD spectrum ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which is the potentially progressive form. NAFLD is associated with metabolic syndrome and insulin resistance. Treatment recommendations include weight reduction through both diet and physical activity, and weight-loss surgery for extreme obesity. Most medical regimens target components of the metabolic syndrome or oxidative stress associated with the pathogenesis of NASH. These include antiobesity regimen... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=1911467 Tue, 28 Oct 2008 12:30:15 +0100 1911467 http://www.medworm.com/index.php?rid=1911466&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1091985 Semin Liver Dis 2008; 28: 407-426DOI: 10.1055/s-0028-1091985ABSTRACTNonalcoholic fatty liver disease (NAFLD) spans a spectrum from simple steatosis to nonalcoholic steatohepatitis (NASH) to cirrhosis. Simple steatosis is the substrate upon which the more serious entities in the spectrum develop; it is the first “hit” in the multistep pathogenesis of NASH, which is considered the hepatic manifestation of the metabolic syndrome. Demonstration of the existence of regulatable fatty acid transport mechanisms has contributed to clarifying the role of fatty acid disposition in obesity, the various components of NAFLD, and the metabolic syndrome. Hepatic steatosis is closely linked to obesity. This linkage is based on the fact that obesity results in marked enlargement of the intraabdo... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=1911466 Tue, 28 Oct 2008 12:30:15 +0100 1911466 http://www.medworm.com/index.php?rid=1911465&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1091984 Semin Liver Dis 2008; 28: 396-406DOI: 10.1055/s-0028-1091984ABSTRACTThe prevalence of obesity and the metabolic syndrome (MS) is on the rise, and subsequently the hepatic manifestation of MS, nonalcoholic fatty liver disease (NAFLD), has become a common entity in clinical practice. Most patients with NAFLD face medical complications related to their underlying MS in other organ systems; however, a small but significant group of patients with the more aggressive form of fatty liver, nonalcoholic steatohepatitis (NASH), are at risk of developing cirrhosis and hepatocellular carcinoma. As patients are generally asymptomatic, often their disease goes unrecognized. This is particularly true for NASH, where liver biopsy is currently required to make the diagnosis. Once diagnosed, no one treatmen... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=1911465 Tue, 28 Oct 2008 12:30:15 +0100 1911465 http://www.medworm.com/index.php?rid=1911464&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1091983 Semin Liver Dis 2008; 28: 386-395DOI: 10.1055/s-0028-1091983ABSTRACTNonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States and many other parts of the world. Its prevalence continues to rise—currently affecting ~20 to 30% of adults and 10% of children in the United States. NAFLD represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign nonprogressive clinical course, to steatohepatitis or NASH, a more serious form of NAFLD that may progress to cirrhosis and end-stage liver disease. Although currently a combination of noninvasive clinically available laboratory and imaging tests may help in the diagnostic evaluation of a patient with suspected NAFLD, a liver biopsy remains the only reliable way ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=1911464 Tue, 28 Oct 2008 12:30:15 +0100 1911464 http://www.medworm.com/index.php?rid=1911463&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1091982 Semin Liver Dis 2008; 28: 380-385DOI: 10.1055/s-0028-1091982ABSTRACTThis review covers the diagnosis and outcomes of histological subphenotypes of nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) in both children and adults. Serious outcomes of NAFLD include cirrhosis, hepatocellular carcinoma, coronary heart disease, and diabetes. The ability to determine differential outcomes by NAFLD subtypes is dependent upon both the adequate assessment of histological subtypes, as well as the appropriate measure of the outcome of interest. Steatohepatitis, which can only be diagnosed by liver biopsy, has a greater risk for both hepatic and systemic complications than simple steatosis. Differences in subphenotypes between children and adults and among children hav... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=1911463 Tue, 28 Oct 2008 12:30:15 +0100 1911463 http://www.medworm.com/index.php?rid=1911462&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1091981 Semin Liver Dis 2008; 28: 370-379DOI: 10.1055/s-0028-1091981ABSTRACTNonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of hepatic pathology, ranging from simple steatosis (also called nonalcoholic fatty liver or NAFL) in its most benign form, to cirrhosis in its most advanced form. Nonalcoholic steatohepatitis (NASH) is an intermediate level of hepatic pathology. Hepatocyte accumulation of triglyceride is a hallmark of NAFL and NASH, but this sometimes subsides once cirrhosis has developed. Triglyceride storage per se is not hepatotoxic. Rather, it is a marker of increased exposure of hepatocytes to potentially toxic fatty acids. NAFL progresses to NASH when adaptive mechanisms that protect hepatocytes from fatty acid-mediated lipotoxicity become overwhelmed and rates of hepat... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=1911462 Tue, 28 Oct 2008 12:30:15 +0100 1911462 http://www.medworm.com/index.php?rid=1911461&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1091980 Semin Liver Dis 2008; 28: 360-369DOI: 10.1055/s-0028-1091980ABSTRACTNonalcoholic fatty liver disease (NAFLD) is characterized by insulin resistance, which results in elevated serum concentration of free fatty acids (FFAs). Circulating FFAs provide the substrate for triacylglycerol formation in the liver, and may also be directly cytotoxic. Hepatocyte apoptosis is a key histologic feature of NAFLD, and correlates with progressive inflammation and fibrosis. The molecular pathways leading to hepatocyte apoptosis are not fully defined; however, recent studies suggest that FFA-induced apoptosis contributes to the pathogenesis of nonalcoholic steatohepatitis. FFAs directly engage the core apoptotic machinery by activating the proapoptotic protein Bax, in a c-jun N-terminal kinase-dependent manne... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=1911461 Tue, 28 Oct 2008 12:30:15 +0100 1911461 http://www.medworm.com/index.php?rid=1911460&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1091979 Semin Liver Dis 2008; 28: 351-359DOI: 10.1055/s-0028-1091979ABSTRACTNonalcoholic fatty liver disease (NAFLD) is the most common liver abnormality in the United States and is strongly associated with the metabolic syndrome. Although many of the risk factors are well defined, the pathogenesis of NAFLD remains poorly understood. Recent studies have implicated several important cellular processes and signaling pathways that are affected by abnormal lipid metabolism, resulting in specific biochemical, histological, and clinical changes associated with NAFLD. Pharmacotherapy for NAFLD is limited and treatments are mainly to minimize risk factors. Understanding the disease pathogenesis is therefore important in identifying individuals with increased susceptibility for disease progression so lifes... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=1911460 Tue, 28 Oct 2008 12:30:15 +0100 1911460 http://www.medworm.com/index.php?rid=1911459&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1091978 Semin Liver Dis 2008; 28: 339-350DOI: 10.1055/s-0028-1091978ABSTRACTNonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver disease in the United States and worldwide. With obesity being an important risk factor universally, NAFLD is now receiving greater attention and is regarded as a public health issue. In addition, as a result of an aging population and the improving control of other major causes of chronic liver disease, such as hepatitis C and hepatitis B, the burden of NAFLD is expected to increase in years to come. Prevalence estimates of this disease vary widely across populations because of differences in methods for diagnosis and/or definition. New strategies for the prevention, diagnosis, and management will be required to alter the course of this ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=1911459 Tue, 28 Oct 2008 12:30:15 +0100 1911459 http://www.medworm.com/index.php?rid=1911458&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1091977 Semin Liver Dis 2008; 28: 337-337DOI: 10.1055/s-0028-1091977© Thieme Medical PublishersGet connected:Table of contents  |  Full text (Source: Seminars in Liver Disease) Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=1911458 Tue, 28 Oct 2008 02:45:39 +0100 1911458 http://www.medworm.com/index.php?rid=1826109&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1085100 Semin Liver Dis 2008; 28: 328-336DOI: 10.1055/s-0028-1085100ABSTRACTA 56-year-old white male painter, with a history of major electrocution and deep thermal injury, developed mental status changes initially ascribed to an acute neurological event. Unexpectedly, magnetic resonance imaging (MRI) of the head showed areas of high signal intensity in the basal ganglia, which can be observed in advanced liver disease. An electroencephalogram (EEG) suggested metabolic encephalopathy and coexistent elevation of ammonia, indicative of significant liver disease. The patient had had a long history of right upper quadrant pain and fluctuation in liver tests following the electrocution trauma. For these symptoms, he underwent surgery 7 years prior to his current presentation of portosystemic encephalop... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=1826109 Thu, 25 Sep 2008 15:12:55 +0100 1826109 http://www.medworm.com/index.php?rid=1826108&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1085099 Semin Liver Dis 2008; 28: 315-327DOI: 10.1055/s-0028-1085099ABSTRACTBoth pregnancy and oral contraception (mainly when estrogen is included) may precipitate the development of Budd–Chiari syndrome in patients with underlying thrombophilia. By contrast, there is little evidence for such a role of pregnancy and oral contraception in women with portal vein thrombosis. In pregnant women, special modalities for anticoagulation are required, whereas the management of portal hypertension can be similar to that recommended in other diseases and settings. Hereditary hemorrhagic telangiectasia may deteriorate during pregnancy and improve after delivery. Hepatic sinusoidal dilatation and hepatic peliosis are classic complications of long-term use of oral contraceptives. The impact of pregnancy ... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=1826108 Thu, 25 Sep 2008 15:12:55 +0100 1826108 http://www.medworm.com/index.php?rid=1826107&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1085098 Semin Liver Dis 2008; 28: 302-314DOI: 10.1055/s-0028-1085098ABSTRACTVascular tumors of the liver in adult patients include cavernous hemangioma, a common benign tumor; epithelioid hemangioendothelioma, a rare, usually low-grade malignant tumor; and angiosarcoma, a rare and very aggressive tumor. All these primary mesenchymal tumors develop on a normal liver and may also affect other organs. Their pathogenesis remains largely unknown. Hepatic tumors are increasingly detected incidentally due to widespread use of modern abdominal imaging techniques. Therefore, reliable noninvasive characterization and differentiation of such liver tumors is of major importance for clinical practice. Hemangioma follows a benign course, and a nonoperative approach for the majority of these lesions is recommend... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=1826107 Thu, 25 Sep 2008 15:12:55 +0100 1826107 http://www.medworm.com/index.php?rid=1826106&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1085097 Semin Liver Dis 2008; 28: 293-301DOI: 10.1055/s-0028-1085097ABSTRACTIn the last few years, the mechanistic role of thrombophilia due to hypercoagulability and of clonal disorders of hemopoiesis such as chromosome Philadelphia-negative chronic myeloproliferative disorders has been increasingly recognized in primary splanchnic vein thrombosis. As in deep venous thrombosis of the lower limbs, the frequent finding of several prothrombotic disorders in the same individual has led to the concept of primary splanchnic vein thrombosis as a multifactorial disease. Significant progress has been made in determining the molecular bases of inherited thrombophilia, and particularly in the identification of molecular markers of clonal disease in the so-called occult or latent myeloproliferative disorders... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=1826106 Thu, 25 Sep 2008 15:12:54 +0100 1826106 http://www.medworm.com/index.php?rid=1826105&cid=s_36624_17_f&fid=36624&url=http%3A%2F%2Fwww.thieme-connect.com%2FDOI%2FDOI10.1055%2Fs-0028-1085096 Semin Liver Dis 2008; 28: 282-292DOI: 10.1055/s-0028-1085096ABSTRACTNoncirrhotic, nontumoral portal vein thrombosis (PVT) is the second most-frequent cause of portal hypertension in the world. General thrombophilic factors can be identified in approximately 60% of patients. PVT may manifest as an acute process. However, the acute episode more frequently is asymptomatic or paucisymptomatic and portal vein thrombosis is misdiagnosed until the development of complications secondary to portal hypertension, such as variceal bleeding or portal biliopathy. Although no randomized controlled trials have been performed, after the diagnosis of acute PVT early initiation of anticoagulation (within 30 days of the onset of symptoms) is recommended to achieve recanalization. In patients with portal caver... Seminars in Liver Disease journals http://www.medworm.com/rss/comments.php?id=1826105 Thu, 25 Sep 2008 15:12:54 +0100 1826105