Raymond T Chung1, Wendy C King2, Marc G Ghany3, Mauricio Lisker-Melman4, Amanda S Hinerman2, Mandana Khalili5, Mark Sulkowski6, Mamta K Jain7, Eun-Young K Choi8, Michael A Nalesnik9, Atul K Bhan10, Gavin Cloherty11, David K Wong12, Richard K Sterling13. 1. Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: chung.raymond@mgh.harvard.edu. 2. University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania. 3. Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. 4. Washington University School of Medicine and John Cochran VA Medical Center, St. Louis, Missouri. 5. University of California San Francisco, San Francisco, California. 6. Johns Hopkins University, Baltimore, Maryland. 7. University of Texas Southwestern Medical Center and Parkland Health & Hospital System, Dallas, Texas. 8. University of Michigan, Ann Arbor, Michigan. 9. University of Pittsburgh, Pittsburgh, Pennsylvania. 10. Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. 11. Abbott Diagnostics, Abbott Park, Illinois. 12. University Health Network, Toronto, Ontario, Canada. 13. Virginia Commonwealth University, Richmond, Virginia.
Abstract
BACKGROUND & AIMS: The contribution of the novel biomarkers, hepatitis B virus (HBV) RNA and HBV core-related antigen (HBcrAg), to characterization of HBV-human immunodeficiency virus (HIV) coinfection is unclear. We evaluated the longitudinal dynamics of HBV RNA and HBcrAg and their association with classical HBV serum biomarkers and liver histology and viral staining. METHODS: HBV-HIV co-infected adults from 8 North American centers entered a National Institutes of Health-funded prospective cohort study. Demographic, clinical, serological, and virological data were collected at entry and every 24 to 48 weeks for up to 192 weeks. Participants with HBV RNA and HBcrAg measured ≥2 times (N = 95) were evaluated; 56 had paired liver biopsies obtained at study entry and end of follow-up. RESULTS: Participants had a median age of 50 years; 97% were on combination anti-viral therapy. In hepatitis B e antigen (HBeAg)+ participants, there were significant declines in HBV RNA and HBcrAg over 192 weeks that tracked with declines in HBeAg, hepatitis B surface antigen, HBV DNA, and hepatitis B core antigen (HBcAg) hepatocyte staining grade (all P < .05). In HBeAg- participants, there were not significant declines in HBV RNA (P = .49) and HBcrAg (P = .63), despite modest reductions in hepatitis B surface antigen (P < .01) and HBV DNA (P = .03). HBV serum biomarkers were not significantly related to change in hepatic activity index, Ishak fibrosis score, or hepatocyte HBcAg loss (all P > .05). CONCLUSIONS: In HBV-HIV coinfected adults on suppressive dually active antiviral therapy, the use of novel HBV markers reveals continued improvement in suppression of HBV transcription and translation over time. The lack of further improvement in HBV serum biomarkers among HBeAg- patients suggests limits to the benefit of combination anti-viral therapy and provide rationale for additional agents with distinct mechanisms of action.
BACKGROUND & AIMS: The contribution of the novel biomarkers, hepatitis B virus (HBV) RNA and HBV core-related antigen (HBcrAg), to characterization of HBV-human immunodeficiency virus (HIV) coinfection is unclear. We evaluated the longitudinal dynamics of HBV RNA and HBcrAg and their association with classical HBV serum biomarkers and liver histology and viral staining. METHODS: HBV-HIV co-infected adults from 8 North American centers entered a National Institutes of Health-funded prospective cohort study. Demographic, clinical, serological, and virological data were collected at entry and every 24 to 48 weeks for up to 192 weeks. Participants with HBV RNA and HBcrAg measured ≥2 times (N = 95) were evaluated; 56 had paired liver biopsies obtained at study entry and end of follow-up. RESULTS: Participants had a median age of 50 years; 97% were on combination anti-viral therapy. In hepatitis B e antigen (HBeAg)+ participants, there were significant declines in HBV RNA and HBcrAg over 192 weeks that tracked with declines in HBeAg, hepatitis B surface antigen, HBV DNA, and hepatitis B core antigen (HBcAg) hepatocyte staining grade (all P < .05). In HBeAg- participants, there were not significant declines in HBV RNA (P = .49) and HBcrAg (P = .63), despite modest reductions in hepatitis B surface antigen (P < .01) and HBV DNA (P = .03). HBV serum biomarkers were not significantly related to change in hepatic activity index, Ishak fibrosis score, or hepatocyte HBcAg loss (all P > .05). CONCLUSIONS: In HBV-HIV coinfected adults on suppressive dually active antiviral therapy, the use of novel HBV markers reveals continued improvement in suppression of HBV transcription and translation over time. The lack of further improvement in HBV serum biomarkers among HBeAg- patients suggests limits to the benefit of combination anti-viral therapy and provide rationale for additional agents with distinct mechanisms of action.
Authors: Christine I Wooddell; Man-Fung Yuen; Henry Lik-Yuen Chan; Robert G Gish; Stephen A Locarnini; Deborah Chavez; Carlo Ferrari; Bruce D Given; James Hamilton; Steven B Kanner; Ching-Lung Lai; Johnson Y N Lau; Thomas Schluep; Zhao Xu; Robert E Lanford; David L Lewis Journal: Sci Transl Med Date: 2017-09-27 Impact factor: 17.956
Authors: Richard K Sterling; Abdus S Wahed; Wendy C King; David E Kleiner; Mandana Khalili; Mark Sulkowski; Raymond T Chung; Mamta K Jain; Mauricio Lisker-Melman; David K Wong; Marc G Ghany Journal: Am J Gastroenterol Date: 2019-05 Impact factor: 10.864
Authors: Florian van Bömmel; Anne Bartens; Alena Mysickova; Jörg Hofmann; Detlev H Krüger; Thomas Berg; Anke Edelmann Journal: Hepatology Date: 2014-11-25 Impact factor: 17.425
Authors: Aleksei Suslov; Marie-Anne Meier; Sylvia Ketterer; Xueya Wang; Stefan Wieland; Markus Hermann Heim Journal: J Hepatol Date: 2020-11-11 Impact factor: 25.083
Authors: Richard K Sterling; Wendy C King; Mandana Khalili; Raymond T Chung; Mark Sulkowski; Mamta K Jain; Mauricio Lisker-Melman; Marc G Ghany; David K Wong; Amanda S Hinerman; Atul K Bhan; Abdus S Wahed; David E Kleiner Journal: Hepatology Date: 2021-08-25 Impact factor: 17.298