Abstract

BackgroundHepatitis B virus (HBV) infection is a major public health problem globally. HBV genotypes and subgenotypes influence disease transmission, progression, and treatment outcome. A study was conducted among treatment naive chronic HBV patients in southern Vietnam to determine the genotypes and subgenotypes of HBV.MethodsA prospective, exploratory study was conducted among treatment naïve chronic HBV patients attending at the Hospital for Tropical Diseases, in Ho Chi Minh City, Vietnam during 2012, 2014 and 2016. HBV DNA positive samples (systematically selected 2% of all treatment naïve chronic patients during 2012 and 2014, and 8% of all treatment naïve chronic patients during 2016) were subjected to whole genome sequencing (WGS) either by Sanger or Illumina sequencing. WGS was used to define genotype, sub-genotype, recombination, and the prevalence of drug resistance and virulence-associated mutations.ResultsOne hundred thirty five treatment naïve chronic HBV patients including 18 from 2012, 24 from 2014, and 93 from 2016 were enrolled. Of 135 sequenced viruses, 72.6% and 27.4% were genotypes B and C respectively. Among genotype B isolates, 87.8% and 12.2% were subgenotypes B4 and B2 respectively. A G1896A mutation in the precore gene was present in 30.6% of genotype B isolates. The genotype C isolates were all subgenotype C1 and 78.4% (29/37) of them had at least one basal core promoter (BCP) mutation. A1762T and G1764 T mutations and a double mutation (A1762T and G1764 T) in the BCP region were significantly more frequent in genotype C1 isolates (p < 0.001).ConclusionHBV genotype B including subgenotype B4 is predominant in southern Vietnam. However, one fourth of the chronic HBV infections were caused by subgenotype C1.

Highlights

  • Hepatitis B virus (HBV) infection is a major public health problem globally

  • Worldwide, an estimated 2 billion people have been infected with the hepatitis B virus (HBV) and of these 250 million suffer from chronic HBV infection [1].HBV infection either leads to spontaneous recovery or to chronic HBV, which causes chronic liver disease, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC) [2]

  • The geolocations of the 135 patients enrolled in the study were mapped; 87 districts were represented from the 26 southern provinces of Vietnam

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Summary

Introduction

Hepatitis B virus (HBV) infection is a major public health problem globally. HBV genotypes and subgenotypes influence disease transmission, progression, and treatment outcome. HBV is a small circular DNA virus (~3.2 kb in length) that contains 4 genes with partially overlapping open reading frames (ORFs). These overlapping ORFs encode the polymerase protein, the surface antigen, the core antigen and the X protein. Criteria for assigning a new subgenotype have been proposed recently [5] They include: i) analysis of full-length genome, ii) adherence to intra-genotypic nucleotide divergence (>4.5% and

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