Browsing by Author "Chung RT"

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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.
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.
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.