title: Hepatitis B virus sequencing and liver fibrosis evaluation in HIV/HBV co-infected Nigerians.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Grant
authors.affiliation: Department of Medicine, University of Jos and Jos University Teaching Hospital, Jos, Nigeria.
authors.forename: Oche
authors.initials: O
authors.lastname: Agbaji
authors.affiliation: School of Clinical Medicine, Faculty of Health Sciences, Hepatitis Virus Diversity Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Anna
authors.initials: A
authors.lastname: Kramvis
authors.affiliation: School of Clinical Medicine, Faculty of Health Sciences, Hepatitis Virus Diversity Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Mukhlid
authors.initials: M
authors.lastname: Yousif
authors.affiliation: HIV Care and Treatment Center, Jos University Teaching Hospital, Jos, Nigeria.
authors.forename: Mu'azu
authors.initials: M
authors.lastname: Auwal
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Penugonda
authors.affiliation: HIV Care and Treatment Center, Jos University Teaching Hospital, Jos, Nigeria.
authors.forename: Placid
authors.initials: P
authors.lastname: Ugoagwu
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Murphy
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Hawkins
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015992:Body Mass Index; D018791:CD4 Lymphocyte Count; D060085:Coinfection / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005838:Genotype; D006678:HIV; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D006509:Hepatitis B / Q000150:complications* / Q000473:pathology / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000473:pathology* / Q000821:virology; D008103:Liver Cirrhosis / Q000209:etiology* / Q000473:pathology / Q000821:virology; D008297:Male; D009154:Mutation; D009549:Nigeria; D011401:Promoter Regions, Genetic
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral
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