These data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-alpha.
To our knowledge, this is the strongest and most significant genetic effect associated with natural clearance of HCV, and these results implicate a primary role for IL28B in resolution of HCV infection.
The association of the IL28B locus with natural and treatment-associated control of HCV indicates the importance of innate immunity and interferon lambda in the pathogenesis of HCV infection.
Association of a single nucleotide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in HIV/hepatitis C virus-coinfected patients.
This review will summarize currently available data on the clinical impact of IL28B polymorphisms on HCV infection and the potential mechanisms for its effects.
This study identified genetic variation near the IL28B gene and aa substitution of the core region as predictors of sustained virological response to a triple therapy of telaprevir/PEG-IFN/ribavirin in Japanese patients infected with HCV genotype 1b.
Recently, genome-wide association studies in patients affected by HCV infection have identified a strong association between sustained virological response to peg-interferon/ribavirin and spontaneous viral clearance and common single nucleotide polymorphisms (SNPs) near the IL28B gene, encoding for interferon-lambda-3.
Genetic analyses of IL28B in patients and donors and of the core and nonstructural protein 5A regions encoded by HCV RNA predicted an SVR with 83% sensitivity and 82% specificity; this was more effective than analysis of any single genetic feature.
Determination of the IL28B genotype and whether patients have an RVR might be used in future studies of patients with hepatitis C virus genotype 1 or 4.
SNPs in the promoter region of IL-28B were first shown to be associated with HCV treatment-induced viral clearance and subsequently to be a key determinant of spontaneous HCV resolution in infected individuals.
In Cox proportional hazards analysis (without IL28B), HCV seroconversion illness with jaundice was the only factor predicting spontaneous clearance (adjusted hazards ratio = 2.86; 95% confidence interval = 1.24, 6.59; P = 0.014).
We review the genetic studies that uncovered the association between IL28B and HCV clearance, the biology of IFN-λ3, the clinical implications of the genetic association, and areas of future research.
The final score included 4 variables: 2 host-related variables (IL28B SNP rs12979860 and liver stiffness) and 2 HCV-related variables (genotype and viral load).
Our findings suggest that IL28B may account for some differences in HCV outcome but that other factors including the viral genotype, host genetics and the host-virus interaction are likely to influence the outcome of HCV infection.
Protective interleukin-28B genotype affects hepatitis C virus clearance, but does not contribute to HIV-1 control in a cohort of African-American elite controllers/suppressors.
The critical role of interleukin-28B (IL28B)/interferon-λ3 (IFN-λ3) polymorphisms on the susceptibility to hepatitis C virus infection and the response to peginterferon-ribavirin therapy has encouraged exploration of similar effects on other viruses.