Carla S Coffin1, Patricia M Mulrooney-Cousins2, Carla Osiowy3, Frank van der Meer4, Sandra Nishikawa5, Tomasz I Michalak2, Guido van Marle6, M John Gill6. 1. Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. Electronic address: cscoffin@ucalgary.ca. 2. Molecular Virology and Hepatology Research Group, Faculty of Medicine, Memorial University, St. John's, Newfoundland and Labrador, Canada. 3. National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada. 4. Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; Faculty of Veterinary Medicine, University of Calgary, AB, Canada. 5. Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. 6. Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Abstract
BACKGROUND: Occult hepatitis B virus infection (OBI) is defined as low-level HBV DNA presence in serum, liver and/or peripheral blood mononuclear cells (PBMC) in individuals that lack serum hepatitis B virus surface antigen (HBsAg). HIV+ patients with OBI may be at risk for HBV reactivation, and often receive dual active anti-HBV/HIV therapy, such as lamivudine (LMV). OBJECTIVES: To determine the presence of OBI in a North American cohort of HIV-1-positive patients. STUDY DESIGN/ METHODS: 45 HIV-1-positive, serum HBsAg-negative patients, reactive for antibodies to HBV core antigen (anti-HBc), were tested for HBV DNA in plasma and for HBV DNA and covalently closed circular DNA (cccDNA) in PBMC. Ten patients were re-tested after ∼5-10 years, including genotyping and clonal sequence analysis of the HBV polymerase (P) gene and overlapping HBV surface (S) gene from 8 PBMC samples. RESULTS: Overall, 42% (19/45) tested HBV DNA positive, especially in PBMC (18/45), including 3/18 that were reactive for HBV cccDNA, compared to 17% (8/45) that were HBV DNA reactive in plasma. In 8 patients on LMV, sequence analysis in PBMC showed that all were HBV genotype C or D. Several carried HBV P region variants at residues associated with anti-HBV drug resistance and overlapping S gene region within the major HBsAg "a determinant". CONCLUSION: OBI is common in HIV-positive, anti-HBc reactive patients on anti-HBV/HIV therapy, particularly in PBMC. HBV sequence analysis revealed that all had HBV genotype C or D and often had P/overlapping S gene variants possibly associated with dual-active anti-HIV/HBV therapy.
BACKGROUND:Occult hepatitis B virus infection (OBI) is defined as low-level HBV DNA presence in serum, liver and/or peripheral blood mononuclear cells (PBMC) in individuals that lack serum hepatitis B virus surface antigen (HBsAg). HIV+ patients with OBI may be at risk for HBV reactivation, and often receive dual active anti-HBV/HIV therapy, such as lamivudine (LMV). OBJECTIVES: To determine the presence of OBI in a North American cohort of HIV-1-positivepatients. STUDY DESIGN/ METHODS: 45 HIV-1-positive, serum HBsAg-negative patients, reactive for antibodies to HBV core antigen (anti-HBc), were tested for HBV DNA in plasma and for HBV DNA and covalently closed circular DNA (cccDNA) in PBMC. Ten patients were re-tested after ∼5-10 years, including genotyping and clonal sequence analysis of the HBV polymerase (P) gene and overlapping HBV surface (S) gene from 8 PBMC samples. RESULTS: Overall, 42% (19/45) tested HBV DNA positive, especially in PBMC (18/45), including 3/18 that were reactive for HBV cccDNA, compared to 17% (8/45) that were HBV DNA reactive in plasma. In 8 patients on LMV, sequence analysis in PBMC showed that all were HBV genotype C or D. Several carried HBV P region variants at residues associated with anti-HBV drug resistance and overlapping S gene region within the major HBsAg "a determinant". CONCLUSION: OBI is common in HIV-positive, anti-HBc reactive patients on anti-HBV/HIV therapy, particularly in PBMC. HBV sequence analysis revealed that all had HBV genotype C or D and often had P/overlapping S gene variants possibly associated with dual-active anti-HIV/HBV therapy.
Authors: Vanessa Meier-Stephenson; Tekalign Deressa; Meaza Genetu; Debasu Damtie; Sheila Braun; Kevin Fonseca; Mark G Swain; Guido van Marle; Carla S Coffin Journal: Can Liver J Date: 2020-11-17
Authors: Z Lee; S Nishikawa; S Gao; J B Eksteen; M Czub; M J Gill; C Osiowy; F van der Meer; G van Marle; C S Coffin Journal: PLoS One Date: 2015-09-21 Impact factor: 3.240
Authors: Annie Y Chen; Matthew Hoare; Arun N Shankar; Michael Allison; Graeme J M Alexander; Tomasz I Michalak Journal: PLoS One Date: 2015-10-16 Impact factor: 3.240