R T Chung

..It has remained unclear how HIV, a nonhepatotropic virus, accelerates the progression of liver disease by HCV...

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..We conducted a multicenter, randomized trial comparing peginterferon plus ribavirin with interferon plus ribavirin for the treatment of chronic hepatitis C in persons coinfected with HIV...

..Eventually, it is anticipated that genotype-phenotype correlations will permit selection of optimized antiviral regimens once virus specific enzymatic inhibitors have been approved...

..We analysed changes in HCV RNA and the frequency of hepatotoxicity in co-infected patient enrolling in AIDS Clinical Trials Group trials, and determined whether HCV impairs successful immune reconstitution in these populations...

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..Further work is needed to develop more-accurate assays for acute HCV infection, to define host and viral factors that predict outcome and to define the optimal duration and regimen of therapy...

..However, after adjusting for drug exposure and accounting for duration of therapy, only neutropenia was independently associated with virologic response...

..The availability of a cell-based test for viral replication will facilitate screening of inhibitory compounds, analysis of IFN-resistance mechanisms, and analysis of virus-host cell interactions...

..Hematologic toxicity and dose modifications were frequent. Our experience with antiviral therapy for HCV post-OLT remains disappointing but PEG-IFN + RBV appears to produce VR in a sizable portion of IFN + RBV non-responders...

..A significant portion of successfully treated patients experience LDL and cholesterol rebound to levels associated with increased coronary disease risk. Lipids should be carefully monitored in persons receiving antiviral therapy...

..Overall, NS5a is not as integral a determinant of interferon responsiveness as previously suggested...

..Levels may increase above pre-infection baseline lipid levels and should be monitored...

..To test the hypothesis that antigen-specific interferon (IFN)gamma responses are correlated with milder liver disease in subjects coinfected with HIV-1 and hepatitis C virus (HCV)...

..These data suggest differential regulation of HCV RNA in the serum and PBMC compartments and may partially explain the limited HCV antiviral response rates observed in coinfected persons...

..These data suggest that broad CD8(+) T-cell responses alone may be insufficient to contain HCV replication, and also that early therapy is effective independent of such responses...

..HCV-monoinfected patients. Reasons for this remain unclear. This study evaluated kinetic parameters and treatment responses in co-infected vs monoinfected patients...

..Finally, we will discuss the rapidly evolving area of therapy, with particular attention to many of the newer agents now in clinical trials, as well as combinations of these agents...

..These data suggest that there are several mechanisms by which suppression of HIV replication and a reconstituted immune system influence diversity of HCV in HIV-HCV-coinfected subjects...

..GBV-C RNA clearance with HCV therapy was associated with neither short-term loss of HIV control nor impaired immune status. The association of GBV-C genotype 2 with higher CD4(+) cell counts merits further study...

..0 mEq/mL. In conclusion, use of decision analysis models can help in therapeutic decisions for patients with HCV-1b...

..The association of anaemia with outcomes in the HCV/HIV coinfected persons undergoing HCV treatment remains unclear...

..The risk of interactions between drugs used to treat hepatitis C and those for HIV, such as between ribavirin and didanosine, needs to be considered before initiating treatment in HIV-HCV-coinfected patients...

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..These data suggest that a defect in cytokine activation may occur in HCV/HIV co-infected persons that limits efficient clearance of HCV from the liver...

..Thus, the identification of more effective and better tolerated agents is a high priority. We applied chemical biology to screen small molecules that regulate HCV...

..The response rates of HCV infection to interferon therapy vary depending on viral and host factors. We hypothesized that key regulators of the IFN signaling pathway are predictive of treatment outcome...

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..We conclude that in cases suggestive of ACR, careful consideration should be given to treatment for recurrent HCV in lieu of or in concert with intensive immunosuppression...

..It is provocative to speculate that extrahepatic HCV diversity may be an important determinant of treatment response and thus warrants additional study, particularly during HCV/HIV coinfection...

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..The trend toward a greater initial viral load decrease in patients with LD grafts and the significantly sharper increase suggest that the liver plays a predominant role in both HCV clearance and replication...

..The high degree of concordance of HCV epitopes identified from liver and PBMC suggests that this strategy is a reasonable alternative to liver biopsy for characterizing the CTL response to HCV in chronically infected persons...

..Our results suggest that an analysis of PD-1 expression alone is not sufficient to predict infection outcome or to determine T-cell functionality in HCV infection...

..The authors sought to determine whether hepatic steatosis is associated with hepatocellular carcinoma (HCC) in a cohort of patients with hepatitis C-related cirrhosis...

..To test the hypothesis that hepatitis C virus (HCV)-specific interferon (IFN)gamma immune responses are correlated with HCV virological response following treatment in subjects with HIV-1 and HCV co-infection...

..We sought to determine the safety, tolerability, and acceptance of postexposure prophylaxis with peginterferon alfa-2b in healthcare workers (HCWs) exposed to blood from HCV-infected patients...

..This article summarizes that conference...

..Higher HCV RNA levels were associated with earlier elevations in HOMA-IR. Collectively, these results provide strong evidence that HCV induces the development of IR...

..To evaluate the role of PKR in HCV-related hepatocellular carcinoma (HCC), we compared PKR and related protein expression in paired tumor (T) and surrounding nontumor (NT) tissue...

..In addition, they show a consistent and profound impairment in cellular immune responses to HCV compared to HIV-1 in HIV-1-HCV-coinfected persons...

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..Here we describe seven unique HCV genotype 4a full genomes, in addition to a single genotype 4d genome, and characterize their sequence diversity in relation to other more closely characterized HCV genotypes...

..Most HCC develops in the cirrhotic liver, but the linkage between cirrhosis and HCC is likely multifactorial. In this review, we summarize current knowledge regarding the pathogenetic mechanisms of viral HCC...

..We aimed to determine the correlations between these alleles and natural outcomes of HCV and determine associated key T-cell responses...

..Overexpression of epidermal growth factor (EGF) in the liver induces transformation to hepatocellular carcinoma in animal models. Polymorphisms in the EGF gene modulate EGF levels...

..On a liver biopsy, the histological features of IgG4-associated cholangitis may be distinctive, and in conjunction with IgG4 immunohistochemical stain, may help distinguish this disease from primary sclerosing cholangitis...

..We sought to determine whether circulating apoptotic markers are altered in acute liver failure (ALF), differ with etiology, or predict clinical outcome in this condition...

..Gaining insight into the mechanisms that underlie the immunopathogenesis of these persistent viral infections could lead to new therapeutic strategies for patients with HCV/HIV-1 coinfection...

..Applying concepts learned in HIV therapeutics will hopefully lead to a prudent and cautious path in HCV treatment paradigms, particularly with respect to drug resistance...

..We assessed the costs, clinical benefits, and cost effectiveness of US surveillance and alternative strategies for HCC in cirrhosis using a computer-based state transition model with parameters derived from available literature...

..For these reasons, nonselective shunt surgery such as the proximal splenorenal or the transjugular intrahepatic portosystemic shunt should not be performed in patients with advanced hepatic schistosomiasis...

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..In this study, LTRs receiving IFN did not have an increased frequency of anti-HLA antibodies. This may partially explain the safety of IFN previously reported in LTRs requiring antiviral therapy...

..CONCLUSION: These results suggest a novel therapeutic approach for the treatment of HCV infection...

..Both animal and limited human studies have shown that RAS inhibition with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor-1 [AT-1] blockers (ARBs) has antifibrogenic properties...

..7; P < 0.003). In conclusion, this study identified known and previously unreported risk factors for severe hepatotoxicity that should be considered before the initiation of ART...

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..Randomized trials to investigate immediate versus delayed treatment of acute hepatitis C infection are warranted. In view of these strongly positive outcomes, increased vigilance for acute hepatitis C becomes essential...

..FCH may in part explain the accelerated development of cirrhosis previously observed among coinfected patients. Clinicians should remain vigilant for FCH in the HIV/HCV population and consider antiviral treatment in this setting...

..Finally, the latter result suggests that our replication model may be useful for identifying agents capable of driving replicating virus into error catastrophe...

..Here we examined the effect of a lymphotropic virus, HIV-1, on the ability of coinfected patients to maintain spontaneous control of HCV infection...

..Results of HCV and HBV treatment trials in HIV-coinfected patients and strategies for patient management are discussed herein...

..This article reviews modifications of current therapies, outlines the viral life cycle and focuses on novel therapeutic agents currently being studied...

..5%. Genotype 1 was found in 83.3% of infected patients. Median HCV RNA level was 6.08x106 IU/mL. High virus loads and genotype 1 prevalence may be important to interferon-based antiviral response rates among coinfected patients...

..This anti-HCV action by ME3738 was synergistically enhanced when combined with IFN-alpha. ME3738 might be a useful anti-HCV drug either with or without IFN-alpha...

..In approximately half of the HCV (+) patients with PTDM, the onset of PTDM was related to the recurrence of allograft hepatitis. Improvement in glycemic control was achieved in the patients who responded to antiviral therapy...

..Together, these data indicate that viral escape from CD8+ T cell responses occurs during human HCV infection and that acute immune selection pressure is of sufficient magnitude to influence HCV evolution...

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..We used an HCV cell-based expression model to examine the interaction between HCV protein expression and host type I IFN signaling components in the Jak-STAT kinase pathway...

..Further studies are warranted to identify noninvasive markers of liver disease for the clinical management of HCV disease, particularly when liver biopsies have not been performed or are contraindicated...

..5 microM). We then synthesized an analog of these compounds with optimized activity...

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..Moreover, these data provide important parameters for evaluation of candidate HCV vaccines, and provide rationale for immunotherapy in chronic HCV infection...

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..CONCLUSIONS: HCV is independently associated with increased IR after OLT. These findings provide a possible pathogenetic basis for the association of DM with HCV...

..Moreover, they show that rare populations of memory CD4 T cells can be studied ex vivo in human diseases...

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..HCV therefore synergizes with weight in the promotion of IR. Steatosis was not a prerequisite for the development of IR, implying that HCV's effects on IR may be independent of steatosis...

..Based on these findings, we would advocate a 12 week period of observation for spontaneous clearance before treatment initiation. If no clearance has occurred by 12 weeks, treatment should be initiated...

..Regardless of which criteria are adopted to define eligibility, strict adherence to the criteria is important to achieve acceptable outcomes...

..Our progress in understanding the molecular underpinnings of interferon treatment failure in HCV infection has resulted in several promising and novel treatment strategies for HCV treatment non-responders...

..This case underscores the importance of restoration of the immune system in the control of hepatitis C virus viremia and disease progression and the need to minimize or obviate immunosuppression in organ transplant recipients...

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..These studies will shed considerable light on HIV-HCV pathogenic interactions and offer a means of productively disrupting these interactions. ..

..By developing investigators committed to patient-oriented research, Dr. Chung has strong confidence that they will follow suit in mentoring their own fellows and faculty, in so doing creating a highly desirable multiplier effect. ..

..These studies will shed considerable light on HIV-HCV pathogenic interactions and offer a means of productively disrupting these interactions. ..

..Second, discovery of hit compounds that positively or negatively regulate HCV replication will ultimately help lead to identification of novel cellular targets that can be exploited to further interrupt the viral lifecycle. ..

..Together, these models will help provide insights into the factors responsible for this devastating complication of chronic HCV infection. ..

..These studies will shed considerable light on HIV-HCV pathogenic interactions and offer a means of productively disrupting these interactions. ..