Bruce Bacon

..These data support the model for HH in which HFE mutations lead to inappropriately low crypt cell iron, with resultant stabilization of DMT1(IRE) mRNA, up-regulation of DMT1, and increased absorption of dietary iron...

..Analysis of mice from crosses between C57BL/6 and AKR mice should allow the mapping and subsequent identification of genes modifying the severity of iron loading in this murine model of HH...

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..The medical literature describes a colorful history of HH with important contributions from faculty at Saint Louis University...

..Resistance needs to be carefully monitored as these newer and more potent drugs are added to IFN and RBV backbone drugs. Adverse events will be more frequent and will require special attention...

..The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines...

..We now are at the cusp of yet another such overhaul with the protease inhibitors about to be introduced into the market...

..Boceprevir, a protease inhibitor that binds to the HCV nonstructural 3 (NS3) active site, has been suggested as an additional treatment...

..With the identification of the HFE gene, we are beginning to unravel many of the mysteries of both normal iron absorption and the disorder of iron metabolism found in patients with HH...

..Future pharmacologic agents are currently in development for patients failing treatment or those who have relapsed...

..Hereditary hemochromatosis is a common inherited disorder of iron metabolism. The gene HFE, which contains two missense mutations (C282Y and H63D), was recently identified...

..The articles in this supplement describe the issues in clinical trial design and the evaluation of evidence from clinical trials in patients with chronic hepatitis C...

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..This study suggests that the combination of IFN and ribavirin is a useful modality of therapy in patients with chronic hepatitis C who did not respond to IFN alone...

..CONCLUSION: Long-term maintenance peginterferon in patients with advanced chronic hepatitis C is associated with an excess overall mortality, which was primarily due to nonliver-related causes among patients with bridging fibrosis...

..The knockout mouse model of HH will facilitate investigation into the pathogenesis of increased iron accumulation in HH and provide opportunities to evaluate therapeutic strategies for prevention or correction of iron overload...

..This however did not reach statistical significance. CONCLUSIONS: Hepatic alpha-smooth muscle actin expression, as a marker of hepatic stellate cell activation appears reversible and tends to correlate with necroinflammatory activity...

..Liver transplantation has been established as an effective therapy for patients with end-stage liver disease...

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..Implications for alcohol-induced hepatic fibrosis and future directions for research will also be discussed...

..The block in intracellular transport, accelerated turnover, and failure of the C282Y protein to be presented normally on the cell surface provide a possible basis for impaired function of this mutant protein in HH...

..These changes do not seem to be associated with clinical signs or complications and triglyceride levels decline while patients are still on therapy and return to normal after stopping...

..These findings also raise the question of whether mutations in the HFE gene can disrupt this association and thereby contribute to some forms of neonatal iron overload...

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..A control group (group 2) of 231 CHC patients was identified by using a 2-year database (January 2000-June 2001) of patients without evidence of greater than 33% steatosis or SH...

..The product of HIC and age is highly sensitive and specific for diagnosis of high-grade fibrosis and can be obtained using MRI...

..We examined the effect of HFE mutations on posttransplantation survival in patients with hepatic iron overload...

..This article reviews the epidemiology, natural history, clinical and economic burden, and screening and treatment options for HCV...

..Palliative measures, including ablative therapy and chemoembolization, can be used. With increasing clinical recognition,hemochromatosis should be diagnosed earlier and progression to cirrhosis and HCC should be minimized...

..In hepatitis C, an increased number of CD14-positive cells are associated with high inflammatory activity...

..The mechanism by which HFE influences hepcidin expression is an area of current investigation and may offer insights into the phenotypic variability observed in persons with mutations in HFE...

..Many patients with hepatitis C cirrhosis and low Model for End-Stage Liver Disease scores are too early for transplant but too thrombocytopenic to treat with interferon...

..We conducted a large, randomized, multinational, noninferiority trial to determine whether similar efficacy could be achieved with only 16 weeks of treatment with peginterferon alfa-2a and ribavirin...

..This study investigated the expression and regulation of protein kinase C (PKC) in HSC...

..The data support further clinical studies of CPG 10101 for treating chronic HCV infection...

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..Two major hypotheses have been proposed to explain the pathogenesis of HFE-related hereditary hemochromatosis: the hepcidin hypothesis and the duodenal crypt cell programming hypothesis...

..We speculate that decreased hepcidin expression relative to body iron stores contributes to the iron homeostasis abnormalities characteristic of HH...

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..The use of the oral chelator deferiprone remains controversial, and work is continuing on the development of new orally effective iron chelators...

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..This study confirms the important role for TFR2 in iron homeostasis and provides a tool for investigating the excess iron absorption and abnormal iron distribution in iron-overload disorders...

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..These observations indicate that the H67D mutation leads to partial loss of Hfe function and can contribute to murine HH...

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..HFE, the protein defective in hereditary hemochromatosis, and transferrin receptor 2 (TfR2) are two novel protein candidates that could be involved in mechanisms of iron transport across the platelet plasma membrane...

..These findings support the concept that the combination of HH-induced iron overload and HCV has a potentiating effect on hepatic fibrogenesis...

..ALT levels are a poor marker of disease severity and/or indication for treatment in patients with chronic hepatitis C...

..IFN monotherapy nonresponder patients tended to have a higher HIC. With IFN plus ribavirin, the sustained virologic response rate was not affected by the HIC...

..Future investigations will refine our knowledge of the mechanisms of action of HFE protein, the phenotypic variability observed in persons homozygous for the C282Y mutation, and the mechanisms responsible for non-HFE-related HH...

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..Diabetes was reported in 35%, 25%, and 9%. The concurrence of clinical and histologic features of steatohepatitis with another chronic liver disease may be a reflection of the frequency of steatohepatitis in the population at large...

..A brief review of the clinical enzymology of AST and methods used to quantify serum macro-AST activity is provided...

..CONCLUSIONS: Aldehydic products of lipid peroxidation do not directly activate HSC in early culture and alternative pathways may be responsible for HSC activation during oxidative stress...

..We found no difference in serum AG with different causes of cirrhosis. We also suggest a lower reference range for normal serum AG...

..In control human liver, Kupffer cells had a very low expression of CD14. These findings suggest that CD14-positive monocytes/macrophages may contribute to the process of hepatic fibrogenesis in HH...

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..This expression pattern suggests the presence of two regulatory mechanisms, the first triggered during acute hepatocellular injury, the second during the progression of chronic liver disease...

..This randomized, dose-ranging, phase 2 study compared the efficacy and safety of entecavir with lamivudine in lamivudine-refractory patients...

..The stimulation of intracellular signaling pathways in HSC by this well-characterized ethanol metabolite may contribute to ethanol-induced hepatic fibrogenesis...

..However, the overall proportion of those with active insurance, the quality of life, and the psychological well-being of these subjects were similar to those of unaffected siblings...

..The demonstration that hepatic stellate cell activation can be suppressed by PKC inhibitors suggests a role for PKC in the regulation of hepatic stellate cell activation...

..This article reports the highlights of the conference and summarizes the main conclusions and implications for clinical and experimental hepatology...

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..Since activated HSC play a key role in hepatic fibrogenesis, these experiments will contribute to an improved understanding of the basic biochemical processes underlying hepatic fibrosis. ..