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

Jennifer Grant*, Oche Agbaji, Anna Kramvis, Mukhlid Yousif, Mu'azu Auwal, Sudhir Penugonda, Placid Ugoagwu, Robert Murphy, Claudia Hawkins

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)744-754
Number of pages11
JournalTropical Medicine and International Health
Volume22
Issue number6
DOIs
StatePublished - Jun 2017

Keywords

  • Nigeria
  • antiretroviral therapy
  • hepatitis B virus
  • human immunodeficiency virus
  • liver fibrosis
  • transient elastography

ASJC Scopus subject areas

  • Parasitology
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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