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Antiviral treatment of hepatitis C virus infection and factors affecting efficacy.

ABSTRACT: Hepatitis C virus (HCV) infection is the leading cause of chronic liver-related diseases, including cirrhosis, liver failure, and hepatocellular carcinoma. Currently, no effective vaccine is available for HCV infection. Polyethylene glycol interferon-? (PegIFN-?) in combination with ribavirin (RBV) is the standard of care (SOC) for chronic hepatitis C. However, the efficacy of PegIFN-? and RBV combination therapy is less than 50% for genotype 1 HCV, which is the dominant virus in humans. In addition, IFN and RBV have several severe side effects. Therefore, strategies to improve sustained virological response (SVR) rates have been an important focus for clinical physicians. The serine protease inhibitors telaprevir and boceprevir were approved by the United States Food and Drug Administration in 2011. The addition of HCV protease inhibitors to the SOC has significantly improved the efficacy of treatments for HCV infection. Several direct-acting antiviral drugs currently in late-stage clinical trials, both with and without peg-IFN and RBV, have several advantages over the previous SOC, including higher specificity and efficacy, fewer side effects, and the ability to be administered orally, and might be optimal regimens in the future. Factors affecting the efficacy of anti-HCV treatments based on IFN-? include the HCV genotype, baseline viral load, virological response during treatment, host IL28B gene polymorphisms and hepatic steatosis. However, determining the effect of the above factors on DAA therapy is necessary. In this review, we summarize the development of anti-HCV agents and assess the main factors affecting the efficacy of antiviral treatments.

SUBMITTER: Zhu Y

PROVIDER: S-EPMC3870549 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Antiviral treatment of hepatitis C virus infection and factors affecting efficacy.

Zhu Yan Y Chen Song S

World journal of gastroenterology 20131201 47

Hepatitis C virus (HCV) infection is the leading cause of chronic liver-related diseases, including cirrhosis, liver failure, and hepatocellular carcinoma. Currently, no effective vaccine is available for HCV infection. Polyethylene glycol interferon-α (PegIFN-α) in combination with ribavirin (RBV) is the standard of care (SOC) for chronic hepatitis C. However, the efficacy of PegIFN-α and RBV combination therapy is less than 50% for genotype 1 HCV, which is the dominant virus in humans. In addi ...[more]

PMID: 24379621

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Project description:UnlabelledBluetongue is a major infectious disease of ruminants caused by bluetongue virus (BTV), an arbovirus transmitted by Culicoides. Here, we assessed virus and host factors influencing the clinical outcome of BTV infection using a single experimental framework. We investigated how mammalian host species, breed, age, BTV serotypes, and strains within a serotype affect the clinical course of bluetongue. Results obtained indicate that in small ruminants, there is a marked difference in the susceptibility to clinical disease induced by BTV at the host species level but less so at the breed level. No major differences in virulence were found between divergent serotypes (BTV-8 and BTV-2). However, we observed striking differences in virulence between closely related strains of the same serotype collected toward the beginning and the end of the European BTV-8 outbreak. As observed previously, differences in disease severity were also observed when animals were infected with either blood from a BTV-infected animal or from the same virus isolated in cell culture. Interestingly, with the exception of two silent mutations, full viral genome sequencing showed identical consensus sequences of the virus before and after cell culture isolation. However, deep sequencing analysis revealed a marked decrease in the genetic diversity of the viral population after passaging in mammalian cells. In contrast, passaging in Culicoides cells increased the overall number of low-frequency variants compared to virus never passaged in cell culture. Thus, Culicoides might be a source of new viral variants, and viral population diversity can be another factor influencing BTV virulence.ImportanceBluetongue is one of the major infectious diseases of ruminants. It is caused by an arbovirus known as bluetongue virus (BTV). The clinical outcome of BTV infection is extremely variable. We show that there are clear links between the severity of bluetongue and the mammalian host species infected, while at the breed level differences were less evident. No differences were observed in the virulence of two different BTV serotypes (BTV-8 and BTV-2). In contrast, we show that the European BTV-8 strain isolated at the beginning of the bluetongue outbreak in 2006 was more virulent than a strain isolated toward the end of the outbreak. In addition, we show that there is a link between the variability of the BTV population as a whole and virulence, and our data also suggest that Culicoides cells might function as an "incubator" of viral variants.

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Antiviral treatment of hepatitis C virus infection and factors affecting efficacy.

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Antiviral treatment of hepatitis C virus infection and factors affecting efficacy.

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