INFLUENCE OF HOST AND VIRAL FACTORS IN HEPATITIS C VIRUS INFECTION: ROLE OF TA REPEAT, IFNL3 AND IFNL4 POLYMORPHISMS IN HCV INFECTION AND OUTCOME OF TREATMENT

Abstract

Hepatitis C virus (HCV) is a serious public health problem affecting 170 million carriers worldwide. It is a leading cause of chronic hepatitis, cirrhosis, and liver cancer and is the primary cause for liver transplantation. HCV genotype 6 (HCV-6) is uniquely prevalent in Southern China and Southeast Asia, contributing to almost 30% of all HCV infections in patients and emigrants from these countries. Our data showed that HCV core antigen (HCVcAg) levels in the serum has emerged as a potential marker for active HCV infection and may be used to evaluate response to antiviral therapy and disease progression. There was an excellent correlation between HCV RNA and HCVcAg concentrations, particularly in HCV/HIV co-infected individuals. Serum levels of HCVcAg were associated with ss469415590 polymorphism. As the HCVcAg assay is a reliable test and has the advantages of being rapid and reproducible, it could be used as an alternative to HCV RNA assays in resource-limited settings. Host genetic factors can affect the outcome of HCV infection resulting in either spontaneous clearance from acute infection without treatment or persistence leading to chronic HCV and liver cirrhosis. The interleukin-28B (IL28B) gene polymorphism is a strong baseline predictor of sustained virological response (SVR) in treatment. The length of thymine–adenine dinucleotide repeats, or (TA)n, in the regulatory region of IL28B can affect interferon transcription. In order to determine predictive values in HCV infection, we explored the correlation among factors including (TA)n genotypes, clinical features, interferon-λ-3 (IFNL3) and interferon-λ-4 (IFNL4) polymorphisms, and HCV treatment outcome. We found that the variation of (TA)n ranged from 6 to 16 and the most frequent (TA)n was 12 in our population. The (TA)n genotypes was not associated with spontaneous clearance of HCV infection but was associated with treatment response in patients infected with HCV-1, HCV-3 and HCV-6. In contrast, IFNL3 and IFNL4 polymorphisms were predictive of treatment outcome only for patients infected with HCV-1. In our meta-analysis study, the PEG-IFN plus RBV combination were effective for HCV-6 patients, with a pooled SVR rate of 79.8% in our study. Moreover, treatment outcomes of HCV-6 patients were superior to HCV-1, and comparable to those of HCV-2 and HCV-3. Regardless of treatment duration and type of PEG-IFN, efficacy of treatment for 48 weeks was superior to that for 24 weeks. The level of fibrosis affected SVR in HCV-6 patients, while sex (male or female) had no significant influence on treatment outcome. Moreover, IL28B and IFNL4 polymorphisms were not significantly associated with treatment outcome in HCV-6 patients.