Role of Viral and Host factors in Treatment Outcomes of Interferon based therapy in Chronic HCV Pakistani patients

Abstract

To date the only standard of care for Hepatitis C virus (HCV) infection is combinational therapy of interferon and ribavirin. Interferon based therapy is a treatment of long duration, associated with cost-effects and serious side-effects. The struggle for discovering new direct-acting antiviral agents (DAAs) against HCV infection is still continued. The researchers are making efforts to use combinational therapy against HCV without the involvement of interferon. The majority of patients are treated with interferon plus weight based ribavirin. Therefore, the present study was designed to search for independent markers that may significantly predict the treatment outcomes of interferon based therapy of HCV infection in Pakistani population. This study would assist the clinic doctors and researchers for personalized treatment of HCV infection. Both viral and host factors were considered for the prediction of interferon based therapy of HCV infection in the present study. There were recruited 140 chronic HCV patients and 120 healthy individuals. In the current study; patient characteristics, single nucleotide polymorphisms (SNPs) of important genes, viral genotypes and baseline viral load were considered. SNPs of the host genome were studied by allele specific polymerase chain reaction (AS-PCR), amplification refractory mutation system polymerase chain reaction (ARMS-PCR), and restriction length polymorphism polymerase chain reaction (RFLP-PCR). HCV genotyping was performed by Ohno method. HCV viral quantification was performed by real time PCR. The results showed that HCV genotype 3 was the most prevalent genotype (81%) with a very high response rate (91%). The distribution of other HCV genotypes was Abstract xxii comparatively less and also showed decreased response rate to interferon based therapy. The level of alanine aminotransferase (ALT) and low baseline viral load were linked with enhanced response rate to combinational therapy of HCV infection. Regarding SNPs in the host genome; SNPs of interleukin 28B (IL28B) clustered RefSNPs (rs) 12979860 and rs8099917, IL18 promoter variants, -607C/A (rs1946518) and -137G/C (rs187238), oligoadenylate synthetase gene 1 (OAS1) at exon 7 splice accepter site (SAS), rs10774671, osteopontin (OPN) -442 C/T (rs11730582), TGF-β1 functional polymorphism at codon 10 T/C (rs1982073) and codon 25 G/C (rs1800471), a single nucleotide variant in intron 6 of GALNT8 rs10849138 were analyzed for their association with natural clearance and interferon based therapy of HCV infection. There was found significant associations of IL28B rs12979860CC genotype, OAS1 rs12979860GG genotype, IL18 -607AA genotype, OPN -442TT genotype with HCV infection and treatment response. In conclusion, HCV genotyping and testing of IL28B polymorphism may be used as predictive markers for the outcomes of interferon based therapy in Pakistani population.