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Hepatitis B virus sequencing and liver fibrosis evaluation in HIV/HBV co-infected Nigerians

Trop Med Int Health. 2017 Jun;22(6):744-754. doi: 10.1111/tmi.12873. Epub 2017 May 22.

Abstract

Objectives: Molecular characteristics of hepatitis B virus (HBV), such as genotype and genomic mutations, may contribute to liver-related morbidity and mortality. The association of these characteristics with liver fibrosis severity in sub-Saharan Africa is uncertain. We aimed to characterise molecular HBV features in human immunodeficiency virus (HIV)/HBV co-infected Nigerians and evaluate associations between these characteristics and liver fibrosis severity before and after antiretroviral therapy (ART) initiation.

Methods: HIV/HBV co-infected Nigerians underwent liver fibrosis estimation by transient elastography (TE) prior to and 36 months after ART initiation. Basal core promoter/precore (BCP/PC) and preS1/preS2/S regions of HBV were sequenced from baseline plasma samples. We evaluated associations between HBV mutations and liver fibrosis severity by univariate and multivariable regression.

Results: At baseline, 94 patients underwent TE with median liver stiffness of 6.4 (IQR 4.7-8.7) kPa. Patients were predominantly infected with HBV genotype E (45/46) and HBe-antigen negative (75/94, 79.8%). We identified BCP A1762T/G1764A in 15/35 (43%), PC G1896A in 20/35 (57%), 'a' determinant mutations in 12/45 (26.7%) and preS2 deletions in 6/16 (37.5%). PreS2 mutations were associated with advanced fibrosis in multivariable analysis. At follow-up, median liver stiffness was 5.2 (IQR 4.1-6.6) kPa. No HBV molecular characteristics were associated with lack of fibrosis regression, although HIV virologic control, body mass index (BMI) and baseline CD4+ T-cell count were associated with a decline in fibrosis stage.

Conclusion: Frequent BCP/PC and preS1/preS2/S mutations were found in ART-naïve HIV/HBV co-infected Nigerians. Median liver stiffness declined after initiation of ART, regardless of pre-ART HBV mutational pattern or virologic characteristics.

Keywords: ART; TAR; VHB; VIH; Nigeria; antiretroviral therapy; elastografía transitoria; fibrose hépatique; fibrosis hepática; hepatitis B virus; human immunodeficiency virus; liver fibrosis; transient elastography; élastographie transitoire.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use
  • Body Mass Index
  • CD4 Lymphocyte Count
  • Coinfection / virology
  • DNA, Viral / analysis
  • Female
  • Genotype*
  • HIV
  • HIV Infections / complications*
  • HIV Infections / virology
  • Hepatitis B / complications*
  • Hepatitis B / pathology
  • Hepatitis B / virology
  • Hepatitis B virus / genetics*
  • Humans
  • Liver / pathology*
  • Liver / virology
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / virology
  • Male
  • Mutation*
  • Nigeria
  • Promoter Regions, Genetic

Substances

  • Anti-Retroviral Agents
  • DNA, Viral