Michael P Manns

..CONCLUSION: Vaniprevir is a potent HCV protease inhibitor with a predictable resistance profile and favorable safety profile that is suitable for QD or BID administration...

..Generally, glycyrrhizin treatment was well tolerated...

..To review long-term safety data from the rollover study ETV-901, focusing on adverse events (AEs) with a potential nucleos(t)ide association...

..This review summarizes the results of SPRINT-2, a phase III double blind, placebo controlled study in which the efficacy and safety of Boceprevir, a new HCV protease inhibitor, was compared to SOC...

..Thus, these cases highlight that clearance of low levels of HCV viremia is possible in the absence of a strong adaptive immune response which might explain the low seroconversion rate after occupational exposure to HCV...

..Therefore, our data do not support an important role of circulating BA in the control of human energy metabolism...

..The aim of the present study was to investigate the clinical and histological efficacy of lactulose in patients with inflammatory bowel disease (IBD), for which probiotic therapy yielded promising results...

..After having shown activation of NBC by carbachol and forskolin in murine colon, we now investigated these pathways in HEK293 cells transiently expressing a GFP-tagged pNBC1 construct...

..In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001) vaccination in patients with advanced HCC...

..Hopefully, new treatment modalities will be available in the near future. Helicase, protease and the RNA polymerase are potential targets to suppress HCV replication and several immunotherapeutic approaches are explored...

..There is increasing interest in identifying patients with chronic hepatitis C genotype 2 or 3 infection in whom it is possible to lower the burden of therapy while retaining high levels of efficacy...

..For most patients with chronic hepatitis B, including those infected neonatally and those with HBeAg-negative disease, safe, tolerable, and effective alternatives to IFN are needed...

..BI201335 is a highly specific and potent HCV protease inhibitor. This multiple rising dose trial evaluated antiviral activity and safety in chronic HCV genotype-1 patients...

..We compared the effects of budesonide (a steroid that is rapidly metabolized, with low systemic exposure) and prednisone, both in combination with azathioprine...

..Further research will be needed to develop optimum and cost-effective treatment strategies for the general HCV-infected population, particularly patients with comorbidities...

..This review describes the efficacy and optimisation of the current standard therapy of hepatitis C and its problems in special patient populations. New treatment directions beyond interferon alpha based therapies are on the horizon...

..If there is any evidence of an aetiological association of replicative hepatitis C infection and the above-mentioned extrahepatic diseases, antiviral treatment should be considered...

..Here we review the specific challenges posed by HCV, and recent developments in the design of vaccines and novel antiviral agents...

..Given the importance of serological testing, the IAHG is also working on guidelines and procedures for more reliable and standardized testing of autoantibodies...

..This review will summarise the current knowledge on pathogenesis, frequency and treatment options of HBV reactivations in patients with impaired immunity...

..In this randomised trial, peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin...

..Antiviral activity of TMC435, an oral, once-daily, HCV NS3/4A protease inhibitor, was evaluated with pegylated interferon-α2a/ribavirin (P/R) in HCV genotype-1 patients...

..Famciclovir therapy was safe and well tolerated; serious adverse events were reported infrequently. Famciclovir treatment may be beneficial in patients with hepatitis B infection post-OLT...

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..Natural killer (NK) cells might be associated with control of HCV infection. We examined the effects of IFNalpha on human NK cells and its relevance to HCV infection...

..However, there is limited information on HBsAg levels considering the dynamic natural course of HBV-infection. This study aimed to determine HBsAg levels in the different phases of HBV-infection in European HBsAg-positive patients...

..These results highlight the importance of blocking these suppressor mechanisms early in the disease in developing immunotherapy protocols...

..Hepatology 2003;38:218-229)...

..However, recent studies described a decline in HCV-specific CD8+ T-cells during interferon treatment, suggesting that the success of acute HCV therapy might be independent of adaptive immunity...

..UGT1A3 transcription was reduced in the presence of promoter SNPs. These data demonstrate xenobiotic induced regulation of the UGT1A3 gene by the AhR, which shows genetic variability...

..With sophisticated differentiation protocols, hepatic gene expression can be induced in a proportion of ES cells with gene expression patterns similar to early fetal liver...

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..Additionally, we identified the IL-6-gp130-STAT3-dependent proteins KC and SAA2 as new candidates for therapeutic targets in liver diseases...

..Taken together, our results demonstrate a secretagogue-induced increase of NBCe1 membrane expression. Vesicle traffic and exocytosis might thus represent a novel mechanism of intestinal NBC activation by secretagogues...

..There is no currently approved treatment. We investigated the safety and efficacy of 48 weeks of treatment with peginterferon alfa-2a plus adefovir dipivoxil, peginterferon alfa-2a alone, and adefovir dipivoxil alone...

..Thus, depending on the efficacy of Fas receptor activation, hepatocytes and nonparenchymal cells can either behave as type I or type II cells...

..845; 95% CI). In conclusion, hepatic caspase activity might play a role in HCV clearance and could also predict the efficacy of antiviral therapy...

..In addition to the better-known factors- including coinfections with HBV and HIV- progression of liver disease is adversely affected by smoking, hepatic steatosis and insulin resistance...

..That is, IM HBIG is not dose-saving; however, it may be cost-effective if the price per unit is lower. Individualized dosing intervals should be further evaluated as a cost-effective alternative to fixed dosing schemes...

..Indinavir (IDV) can lead to hyperbilirubinemia in Gilbert's syndrome (UGT1A1*28), which does not explain interindividual severity differences and may thus involve additional UGT1A variants...

..We performed anti-HDV IgM testing in a well defined cohort of HDV-infected patients who were treated with pegylated interferon-α2a plus adefovir, or either drug alone...

..Of note, both patients recovered from their initial unconjugated hyperbilirubinemia despite continuation of ribavirin therapy, which indicates that compensatory mechanisms leading to a normalization of UGT1A1 activity are likely...

..Interestingly, siRNA seems a promising innovative treatment option to inhibit specifically HBV replication in vivo...

..In summary, our data show that the IL-4 effects on human intestinal mast cell functions are reversible and accompanied by an increased activity of ERK1/2 and c-Fos...

..Monitoring of HBsAg levels can be useful in individualizing optimal treatment duration in HBV-infected patients...

..As quantitative assays for HBsAg recently became available, we have investigated whether quantitative HBsAg measurements can substitute for hepatitis B virus (HBV) DNA quantification in treatment monitoring...

..UDP glucuronosyltransferases (UGT1A) are proteins with indirect antioxidant, cytoprotective, and genoprotective capabilities; we examined UGT1A regulation in response to coffee in cultured cells and mice...

..We suggest that CD49d can be used as an alternative marker for Gr-1 to differentiate between the subpopulations of MDSCs together with CD11b, which will ultimately help in understanding the mechanisms of immune suppression by MDSCs...

..A quantitative HCV core antigen (HCVcoreAg) immunoassay has been developed for the confirmation of viremia in patients with hepatitis C...

..The role of the adaptive immune system in controlling HDV infection during spontaneous or treatment-induced viral clearance is not well understood...

..The exact mechanisms underlying the antiviral and antitumor effects of IFNalpha are not completely understood. In this study, we investigated if the pro-apoptotic factor caspase-8 is a target gene of IFNalpha signalling...

..However, these drugs worsen hepatitis C virus (HCV) recurrence after liver transplantation, suggesting that they may directly exacerbate HCV infection...

..The expression of Cul3 during hepatic differentiation therefore safeguards against the formation of progenitor cells that carry a great potential for transformation into tumor-initiating cells...

..Here, for the first time, we have identified and analyzed their role in inflammatory bowel disease (IBD)...

..AhR-mediated regulation of the human UGT1A4 gene by two XRE and a modulation by naturally occurring genetic variability by SNPs is demonstrated, which indicates gene-environment interaction with potential relevance for drug metabolism...

..Our data establish a central role for Nrf2 in the protection against Faa-induced liver injury; the Nrf2 regulated cellular defense not only prevents acute Faa-induced liver failure but also delays hepatocarcinogenesis in HT1...

..To define the IL-6-dependent intracellular pathways more specifically, we generated a hepatocyte-specific gp130 knockout mouse...

..The accuracy of these parameters in predicting transplantation or death shows significant variation in different countries...

..CONCLUSION: We provide evidence that mTOR inhibition has a substantial effect on sequential carcinogenesis and may offer an effective strategy to delay liver tumor development in patients at risk...

..In conclusion, MMP expression during the course of chronic hepatitis C appears to be a closely regulated process, with different clusters of coordinately regulated MMP genes being identified...

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..Further studies should address the question, of whether the use of potent adjuvant systems results in higher response rates...

..NY-ESO-1, a member of the cancer testis antigen family, is one possible candidate for a tumor-specific antigen in HCC. The aim of this study was to show the relevance of NY-ESO-1 in hepatocellular carcinoma...

..The aim of our study was to search for highly up-regulated genes in primary malignant liver tumours and to analyse their expression at the mRNA- and protein level...

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..In summary, the degree of tumor selectivity of viral replication marginally influences antitumoral immune responses, but is a major determinant of antivector immunity and systemic toxicity...

..Studies have shown that serum HBsAg quantification during, and at end of, treatment may predict long-term HBsAg loss...

..Moreover, Adp53sensor provides a strategy that should be applicable to other transcriptionally regulated DNA viruses...

..Increased oxidative stress has been implicated in the pathophysiology of many diseases including ethanol-induced liver disease. Therefore, the role of Nrf2(-/-) in ethanol-induced liver injury was investigated...

..Glucuronidation and its variability are likely to represent an important factor for individualized drug therapy and risk prediction impacting the drug development and licensing processes...

..The method utilizes a technological platform that is widely used in clinical practice and could therefore be easily adapted for routine clinical applications...

..Therefore, we demonstrate that ME3738 triggers IL-6 expression, which activates pathways that are relevant to protect from Con A-induced liver failure...

..Reverse transcriptase-polymerase chain reaction analysis showed Tankyrase-2 expression in human pancreatic tumour. These findings show the relevance of spontaneous murine tumour models for the identification of human tumour antigens...

..In contrast, a sustained response concerning HCV is durable. We recommend long-term monitoring of HBV/HCV-co-infected patients after IFN a-based therapies...

..These data suggest that inhibition of the IMPDH seems not to be the major mechanism of ribavirin in enhancing the antiviral effect of interferon alfa in chronic hepatitis C...

..Thus our results suggest that the role of gp130-dependent signaling is not a direct influence on cell cycle progression after partial hepatectomy but is to activate protective pathways important to enable hepatocyte proliferation...

..However, motivation and compliance are requisites and a CIFN induction is not required...

..This review describes recent advances in the treatment of HCV infection with PEGylated interferon (interferon modified with polyethylene glycol [PEG] ) combined with ribavirin...

..Finally, immunotherapies to enhance HCV-specific immune responses are also attractive strategies to control HCV infection and to prevent chronic liver disease...

..Pre-emptive antiviral treatments should be administered since delayed antiviral treatment is frequently unable to prevent liver failure...

..Earlier initiation might even have prevented the need of liver transplantation. Thus, in patients with pre-existing liver cirrhosis an early switch to adefovir dipivoxil appears indicated after emergence of lamivudine resistance...

..Only limited data is available on the frequency and clinical significance of very low hepatitis C viremia (<600 IU/ml) determined by novel sensitive methods for HCV quantification...

..Further trials are urgently needed to clarify the role of different immunosuppressive compounds in hepatitis C after transplantation...

..The lamivudine-enhanced replication shown by these mutants suggests that continuation of therapy with lamivudine could be deleterious in some patients...

..The efficacy of pegylated interferon alpha and ribavirin in HBV/HCV co-infected patients is unknown...

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..The combination of PEG-interferon and ribavirin improves the overall sustained response rates to 54-56% and represents the new standard therapy for patients with chronic hepatitis C infection in most patients...

..HBV/HCV coinfection is not uncommon with an estimated 7 - 20 million individuals affected worldwide. Patients with HBV/HCV coinfection have an increased risk for cirrhosis, hepatocellular carcinoma (HCC) and even death...

..Established staging systems (Child-Pugh, Okuda and UICC classification) were compared with new prognostic scores from Italy (CLIP) and Spain (BCLC)...

..Our results show that the presence of HLA-DRB1*11 and HLA-DQB1*03 alleles is associated with a reduced risk for the development of HCV induced end stage liver disease...

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..Aim was to investigate possible underlying causes of presumed cryptogenic liver disease...

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..Thus, we suggest treating all patients with HCV-genotype 2 and 3 for only 24 weeks when PEG-IFN alpha-2b is used in combination with ribavirin...

..Exposure to HBV is surprisingly high, and the number of hepatitis C virus (HCV)-positive individuals was also higher than those reported from Western European areas...

..Nuclear factor of activated T cells and NF-kappaB seem to be necessary for the induction of TNF-alpha, IL-3, and IL-13 but are less important for the transcription of IL-5...