Browsing by Author "Bhattacharya D"
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Item Chronic hepatitis B virus monoinfection at a university hospital in Zambia.(2018-Sep-27) Vinikoor MJ; Sinkala E; Kanunga A; Muchimba M; Nsokolo B; Chilengi R; Wandeler G; Mulenga J; Chisenga T; Bhattacharya D; Saag MS; Foster G; Fried MW; Kelly P; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, United States.; Zambian Ministry of Health, Ndeke House, Lusaka 30205, Zambia.; Zambia National Blood Transfusion Service, Private Bag RW1X Ridgeway, Lusaka 50110, Zambia.; Department of Medicine, University of California at Los Angeles, Los Angeles, CA 90035, United States.; Tropical Gastroenterology and Nutrition Group, School of Medicine, University of Zambia, Lusaka 50110, Zambia.; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, United States.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern 3012, Switzerland.; Centre for Infectious Disease Research in Zambia, Lusaka 34681, Zambia.; Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London E1 2AT, United Kingdom.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)AIM: To characterize antiviral therapy eligibility among hepatitis B virus (HBV)-infected adults at a university hospital in Zambia. METHODS: Hepatitis B surface antigen-positive adults ( RESULTS: The median age was 33 years, 71.9% were men, and 30.9% were diagnosed with HBV through a clinically-driven test with the remainder identified CONCLUSION: Approximately one in ten HBV-monoinfected Zambians were eligible for antivirals. Many had indeterminate phenotype and needed clinical follow-up.Item Hepatitis B viral replication markers and hepatic fibrosis in untreated chronic hepatitis B virus infection with and without HIV coinfection in Zambia.(2023-Nov-01) Muula GK; Bosomprah S; Sinkala E; Nsokolo B; Musonda T; Hamusonde K; Bhattacharya D; Lauer G; Chung RT; Mulenga LB; Wandeler G; Vinikoor MJ; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Division of Infectious Diseases, University of California at Los Angeles, Los Angeles, California.; Department of Medicine, Levy Mwanawasa Medical University, Lusaka, Zambia.; School of Public Health, University of Ghana, Accra, Ghana.; Department of Medicine, University of Zambia.; Division of Gastroenterology, Massachusetts General Hospital, Boston, USA.; Department of Infectious Diseases, Bern University Hospital.; Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; University Teaching Hospital, Zambian Ministry of Health.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: To inform novel therapies, a more nuanced understanding of HIV's impact on hepatitis B virus (HBV) natural history is needed, particularly in high burden countries. METHODS: In Lusaka, Zambia, we compared prospectively recruited adults (18+ years) with chronic HBV infection, with and without HIV. We excluded those with prior antiviral treatment experience or HBV diagnosis due to clinical suspicion (rather than routine testing). We assessed HBV DNA levels, hepatitis B e antigen (HBeAg), CD4 + (if HIV coinfection), and liver disease (transient elastography, serum alanine aminotransferase). In multivariable analyses, we evaluated the association of HIV overall and by level of CD4 + count on these markers. RESULTS: Among 713 adults analyzed, median age was 33 years, 63% were male, and 433 had HBV/HIV coinfection. Median CD4 + count was 200 cells/μl. HBV DNA was greater than 2000 IU/ml for 311 (51.0%) and 227 (32.5%) were HBeAg-positive. 15.5% had advanced fibrosis or cirrhosis. HIV coinfection was associated with five-fold increased HBV DNA levels [adjusted geometric mean ratio, 5.78; 95% confidence interval (CI), 2.29-14.62] and two times the odds of HBeAg-positivity (adjusted odds ratio, 2.54; 95% CI, 1.59-4.08). These associations were significant only at CD4 + counts 100-350 and <100 cells/μl. HIV was not associated with markers of fibrosis or ALT. DISCUSSION: HIV's impact on HBV natural history likely depends on the degree and duration of immune suppression. There is strong rationale to monitor HBV DNA in people with HBV/HIV coinfection and immune suppression. A better understanding is needed of mechanisms of increased liver-related mortality in people with HBV/HIV coinfection.Item High Rates of Hepatitis B Virus (HBV) Functional Cure Among Human Immunodeficiency Virus-HBV Coinfected Patients on Antiretroviral Therapy in Zambia.(2020-Jan-02) Chihota BV; Wandeler G; Chilengi R; Mulenga L; Chung RT; Bhattacharya D; Egger M; Vinikoor MJ; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, South Africa.; Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.; Liver Center and Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Ministry of Health, Lusaka, Zambia.; School of Medicine, University of Zambia, Lusaka, Zambia.; Institute of Social and Preventative Medicine, University of Bern, Bern, Switzerland.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)Among 284 human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected adults starting tenofovir-based antiretroviral therapy (ART) in Zambia, median baseline CD4+ count was 202 cells/mm3 and 41.6% were hepatitis B e-antigen positive. Within 2 years of therapy, 29 (10.2%) participants experienced HBV functional cure (confirmed loss of hepatitis B surface antigen). In multivariable analysis, baseline CD4 count <350 cells/mm3, female sex, and lower baseline HBV deoxyribonucleic acid were associated with increased odds of functional cure. Immune recovery during HIV-HBV treatment with ART may drive higher rates of functional cure than during HBV monoinfection treatment. Understanding the mechanisms underlying this phenomenon could inform immunomodulatory therapies for HBV cure.Item Long-term Hepatitis B and Liver Outcomes Among Adults Taking Tenofovir-Containing Antiretroviral Therapy for HBV/HIV Coinfection in Zambia.(2024-Jun-14) Vinikoor MJ; Hamusonde K; Muula G; Asombang M; Riebensahm C; Chitundu H; Sunkuntu-Sichizya V; Bhattacharya D; Sinkala E; Lauer G; Chung R; Mbewe W; Egger M; Bosomprah S; Wandeler G; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Kanyama Level 1 Hospital, Ministry of Health, Lusaka, Zambia.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Department of Medicine, University Teaching Hospital, Lusaka, Zambia.; Department of Radiology, University Teaching Hospital, Lusaka, Zambia.; Research Department, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; School of Medicine, University of Zambia, Lusaka, Zambia.; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.; Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: Long-term outcomes of tenofovir-containing antiretroviral therapy (ART) for hepatitis B virus (HBV)/human immunodeficiency virus (HIV) coinfection were evaluated in Zambia. METHODS: A prospective cohort of adults with HIV and hepatitis B surface antigen (HBsAg)-positivity was enrolled at ART initiation. On tenofovir-containing ART, we ascertained HBV viral load (VL) non-suppression, alanine aminotransferase (ALT) elevation, serologic end-points, progression of liver fibrosis based on elastography, and hepatocellular carcinoma (HCC) incidence. We also described a subgroup (low HBV VL and no/minimal fibrosis at baseline) that, under current international guidelines, would not have been treated in the absence of their HIV infection. RESULTS: Among 289 participants at ART start, median age was 34 years, 40.1% were women, median CD4 count was 191 cells/mm3, 44.2% were hepatitis B e antigen-positive, and 28.4% had liver fibrosis/cirrhosis. Over median 5.91 years of ART, 13.6% developed HBV viral non-suppression, which was associated with advanced HIV disease. ALT elevation on ART was linked with HBV VL non-suppression. Regression of fibrosis and cirrhosis were common, progression to cirrhosis was absent, and no cases of HCC were ascertained. HBsAg seroclearance was 9.4% at 2 and 15.4% at 5 years, with higher rates among patients with low baseline HBV replication markers. CONCLUSIONS: Reassuring long-term liver outcomes were ascertained during tenofovir-based ART for HBV/HIV coinfection in Zambia. Higher than expected HBsAg seroclearance during ART underscores the need to include people with HIV in HBV cure research.Item New Window Into Hepatitis B in Africa: Liver Sampling Combined With Single-Cell Omics Enables Deep and Longitudinal Assessment of Intrahepatic Immunity in Zambia.(2024-Nov-15) Musonda T; Wallace MS; Patel H; Martin OP; Oetheimer C; Mwakamui S; Sinkala E; Nsokolo B; Kanunga A; Lauer G; Chung RT; Wandeler G; Bhattacharya D; Kelly P; Alatrakchi N; Vinikoor MJ; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Division of Infectious Diseases, University of California Los Angeles, Los Angeles, California, USA.; Blizard Institute, Queen Mary University of London, London, United Kingdom.; Tropical Gastroenterology and Nutrition Group, University of Zambia, Lusaka, Zambia.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of Medicine, Levy Mwanawasa University Teaching Hospital, Lusaka, Zambia.; Division of Infectious Diseases, University of Alabama Birmingham, Birmingham, Alabama, USA.; Department of Research, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Medicine, University Teaching Hospital, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)In Lusaka, Zambia, we introduced liver fine-needle aspiration biopsy (FNAB) into a research cohort of adults with treatment-naive chronic hepatitis B virus (HBV) infection, with and without human immunodeficiency virus (HIV) coinfection, as well as with acute HBV infection. From 117 enrollment and 47 longitudinal FNABs (at 1-year follow-up), we established participant acceptability and safety. We also demonstrated the quality of the material through single-cell RNA sequencing of selected enrollment FNAs, which revealed a range of immune cells. This approach can drive new insights into HBV immunology, informing cure strategies, and can improve our understanding of HBV natural history in Africa.