Phylogenetic Diversity in Core Region of Hepatitis C Virus Genotype 1a as a Factor Associated with Fibrosis Severity in HIV-1-Coinfected Patients

Abstract

High hepatitis C virus (HCV) genetic diversity impacts infectivity/pathogenicity, influencing chronic liver disease progression associated with fibrosis degrees and hepatocellular carcinoma. HCV core protein is crucial in cell-growth regulation and host-gene expression. Liver fibrosis is accelerated by unknown mechanisms in human immunodeficiency virus-1- (HIV-1-) coinfected individuals. We aimed to study whether well-defined HCV-1a core polymorphisms and genetic heterogeneity are related to fibrosis in a highly homogeneous group of interferon-treated HIV-HCV-coinfected patients. Genetic heterogeneity was weighed by Faith's phylogenetic diversity (PD), which has been little studied in HCV. Eighteen HCV/HIV-coinfected patients presenting different liver fibrosis stages before anti-HCV treatment-initiation were recruited. Sampling at baseline and during and after treatment was performed up to 72 weeks. At inter/intrahost level, HCV-1a populations were studied using molecular cloning and Sanger sequencing. Over 400 complete HCV-1a core sequences encompassing 573 positions of C were obtained. Amino acid substitutions found previously at positions 70 and 91 of HCV-1b core region were not observed. However, HCV genetic heterogeneity was higher in mild than in severe fibrosis cases. These results suggest a potential utility of PD as a virus-related factor associated with chronic hepatitis C progression. These observations should be reassessed in larger cohorts to corroborate our findings and assess other potential covariates.

Before Direct-Acting Antivirals for Hepatitis C Virus: Evaluation of Core Protein R70Q and L/C91M Substitutions in Chronically Infected Brazilian Patients Unresponsive to IFN and/or RBV

“…In this study, we identified three individuals with R70P, two HCV-GT1a and one HCV-GT1b; one R70P individual presented with cirrhosis (F4); and all three had steatosis. This substitution has only been previously reported in Argentinian and Swedish patients, but no association has been reported [ 28 , 33 ]. A meta-analysis showed that the frequency of 70P was 3% in genotype 3 and 13% in genotype 6 [ 28 ].…”

Genetic Diversity of Hepatitis C Virus Genotype 3a Based on Complete Core Protein in Peshawar, Pakistan

“…Particularly, amino acid substitutions at positions 70 and 91 in the HCV core region have been identified as predictors of hepatocellular carcinoma (HCC) among genotype 1b-infected patients from Japan (14). Hence, these polymorphisms might be considered surrogate markers for hepatic disease stages or the eventual development to HCC (15). Although there is consensus on HCV genotype 3a prevalence in Pakistan, variable frequencies of other HCV genotypes have been reported (16).…”