Mayaphi, Simnikiwe HoratiousMartin, Desmond J.Mphahlele, M. JeffreyBlackard, Jason T.Bowyer, Sheila Mary2013-10-302014-09-012013-11Mayaphi, SH, Martin, DJ, & Mphahlele, MJ, Blackard, JT & Bowyer, SM 2013, 'Variability of the preC/C region of hepatitis B virus genotype A from a South African cohort predominantly infected with HIV', Journal of Medical Virology, vol. 85, no. 11, pp. 1883-1892.0146-6015 (print)1096-9071 (online)10.1002/jmv.23695http://hdl.handle.net/2263/32209Hepatitis B virus (HBV) is a serious global health problem, and HBV genotype is an important determinant of disease progression and treatment outcome. The aim of this study was to assess variations of the precore/core (preC/C) region in HBV genotype A. Sequencing of the preC/C and surface (S) genes of HBV was performed on plasma samples from 20 HBV/HIV co-infected and 5 HBV mono-infected individuals. All preC/C study sequences clustered with subgenotype A1, except for two which clustered with subgenotype D4 reference strains. The nucleotide and amino acid variability was far higher in the preC/C region than in the S region. Mutations associated with reduction or failure of HBV e-antigen (HBeAg) production were observed, with a preC start codon mutation being common (24%). Other mutations (e.g., P5H/L and I97L) associated with severe liver disease were also noticed, some of which were located in the major histocompatibility restricted sites. PreC/C intergenotype nucleotide divergence was >7%, while subgenotypes differed by 2.5–7%. Several study sequences were highly divergent from other African subgenotype A1 strains. This study showed that HBeAg-negative chronic hepatitis B is underestimated in subgenotype A1, and also highlighted the variant South African A1 strains. The major advantage of preC/C sequencing is that it informs patient management as HBeAg-negative chronic hepatitis B responds poorly to conventional interferon-α therapy, and some guidelines treat HBeAg-negative chronic hepatitis B differently from HBeAg-positive chronic hepatitis B. These data suggest that subgenotype A1 may be more involved in severe HBV-related diseasesen© 2013 Wiley Periodicals, Inc.This is the pre-peer reviewed version of the following article : Variability of the preC/C region of hepatitis B virus genotype A from a South African cohort predominantly infected with HIV. Journal of Medical Virology. Vol. 85, no. 11, pp. 1883-1892, 2013, doi : 10.1002/jmv.23695, which has been published in final form at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1096-9071/HBeAg-negative chronic hepatitis BMutationsGenotypingNucleotidesAmino acid (AA)Hepatitis B virus (HBV)Postprint Article