Jennifer Grant1, Oche Agbaji2, Anna Kramvis3, Mukhlid Yousif3, Mu'azu Auwal4, Sudhir Penugonda1, Placid Ugoagwu4, Robert Murphy1, Claudia Hawkins1. 1. Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 2. Department of Medicine, University of Jos and Jos University Teaching Hospital, Jos, Nigeria. 3. School of Clinical Medicine, Faculty of Health Sciences, Hepatitis Virus Diversity Research Unit, University of the Witwatersrand, Johannesburg, South Africa. 4. HIV Care and Treatment Center, Jos University Teaching Hospital, Jos, Nigeria.
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.
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%), PCG1896A 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-ARTHBV mutational pattern or virologic characteristics.
Authors: S Seddigh-Tonekaboni; J A Waters; S Jeffers; R Gehrke; B Ofenloch; A Horsch; G Hess; H C Thomas; P Karayiannis Journal: J Med Virol Date: 2000-02 Impact factor: 2.327
Authors: Nimzing G Ladep; Olufunmilayo A Lesi; Pantong Mark; Maud Lemoine; Charles Onyekwere; Mary Afihene; Mary Me Crossey; Simon D Taylor-Robinson Journal: World J Hepatol Date: 2014-11-27
Authors: Joseph C Forbi; Gilberto Vaughan; Michael A Purdy; David S Campo; Guo-liang Xia; Lilia M Ganova-Raeva; Sumathi Ramachandran; Hong Thai; Yury E Khudyakov Journal: PLoS One Date: 2010-07-19 Impact factor: 3.240
Authors: Jeffrey D Stanaway; Abraham D Flaxman; Mohsen Naghavi; Christina Fitzmaurice; Theo Vos; Ibrahim Abubakar; Laith J Abu-Raddad; Reza Assadi; Neeraj Bhala; Benjamin Cowie; Mohammad H Forouzanfour; Justina Groeger; Khayriyyah Mohd Hanafiah; Kathryn H Jacobsen; Spencer L James; Jennifer MacLachlan; Reza Malekzadeh; Natasha K Martin; Ali A Mokdad; Ali H Mokdad; Christopher J L Murray; Dietrich Plass; Saleem Rana; David B Rein; Jan Hendrik Richardus; Juan Sanabria; Mete Saylan; Saeid Shahraz; Samuel So; Vasiliy V Vlassov; Elisabete Weiderpass; Steven T Wiersma; Mustafa Younis; Chuanhua Yu; Maysaa El Sayed Zaki; Graham S Cooke Journal: Lancet Date: 2016-07-07 Impact factor: 79.321
Authors: Joshua Tognarelli; Nimzing G Ladep; Mary M E Crossey; Edith Okeke; Mary Duguru; Edmund Banwat; Simon D Taylor-Robinson Journal: Niger Med J Date: 2015 Jul-Aug