TY - JOUR
T1 - A Prospective Cohort Study of Novel Markers of Hepatitis B Virus Replication in Human Immunodeficiency Virus Coinfection
AU - HBV-HIV Cohort Study of the Hepatitis B Research Network
AU - Chung, Raymond T.
AU - King, Wendy C.
AU - Ghany, Marc G.
AU - Lisker-Melman, Mauricio
AU - Hinerman, Amanda S.
AU - Khalili, Mandana
AU - Sulkowski, Mark
AU - Jain, Mamta K.
AU - Choi, Eun Young K.
AU - Nalesnik, Michael A.
AU - Bhan, Atul K.
AU - Cloherty, Gavin
AU - Wong, David K.
AU - Sterling, Richard K.
N1 - Funding Information:
Funding This study was funded by Abbott Diagnostics as an ancillary study of the Hepatitis B Research Network (HBRN) to Dr Richard K. Sterling. The authors acknowledge the use of HBRN samples and data as the sole contribution of the HBRN. The HBRN was funded as a Cooperative Agreement between the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the following investigators Lewis R. Roberts, MB, ChB, PhD (U01-DK082843), Anna Suk-Fong Lok, MD (U01-DK082863), Steven H. Belle, PhD, MScHyg (U01-DK082864), Kyong-Mi Chang, MD (U01-DK082866), Michael W. Fried, MD (U01-DK082867), Adrian M. Di Bisceglie, MD (U01-DK082871), William M. Lee, MD (U01-DK082872), Harry L. A. Janssen, MD, PhD (U01-DK082874), Daryl T-Y Lau, MD, MPH (U01-DK082919), Richard K. Sterling, MD, MSc (U01-DK082923), Steven-Huy B. Han, MD (U01-DK082927), Robert C. Carithers, MD (U01-DK082943), Mandana Khalili, MD (U01-DK082944), an interagency agreement with NIDDK: Lilia M. Ganova-Raeva, PhD (A-DK-3002-001) and support from the intramural program, NIDDK, National Institutes of Health (NIH): Marc G. Ghany, MD. Additional funding to support this study was provided to Kyong-Mi Chang, MD, the Immunology Center (NIH/NIDDK Center of Molecular Studies in Digestive and Liver Diseases P30DK50306, NIH Public Health Service Research Grant M01-RR00040), Richard K. Sterling, MD, MSc (UL1TR000058, NCATS (National Center for Advancing Translational Sciences, NIH), Mandana Khalili, MD (CTSA Grant Number UL1TR000004), Michael W. Fried, MD (CTSA Grant Number UL1TR001111), and Anna Suk-Fong Lok (CTSA Grant Number UL1RR024986 and U54TR001959.) Additional support was provided by Gilead Sciences, Inc. and Roche Molecular Systems via a Cooperative Research and Development Agreement (CRADA) through the NIDDK. Conflicts of interest These authors disclose the following: Raymond T. Chung was partially supported by NIH R01AI155140 and has received research grants to his institution from Abbvie, Gilead Sciences, BMS, Roche, Boehringer, Merck, Janssen, and GSK. Mauricio Lisker-Melman reports speakers? bureau for AbbVie and Gilead. Mandana Khalili was partially supported by K24AA022523 and is a recipient of research grant (to her institution) from Gilead Sciences Inc, and Intercept Pharmaceuticals, and has served as consultant for Gilead Sciences Inc. Mark Sulkowski is a consultant and receives research support from Gilead. Mamta K. Jain reports support from Gilead Sciences, Janssen, Merck, and GSK/ViiV. Gavin Cloherty is an employee and shareholder of Abbott. David K. Wong reports research grants to his institution from Gilead, BMS, Vertex, and Boehringer. Richard K. Sterling has received research grants from Gilead, Abbott, Abbvie, and Roche to the University. He also has served on the Data Safety Monitoring Boards for Pfizer and AskBio. The remaining authors disclose no conflicts.
Funding Information:
Funding This study was funded by Abbott Diagnostics as an ancillary study of the Hepatitis B Research Network (HBRN) to Dr Richard K. Sterling. The authors acknowledge the use of HBRN samples and data as the sole contribution of the HBRN. The HBRN was funded as a Cooperative Agreement between the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the following investigators Lewis R. Roberts, MB, ChB, PhD (U01-DK082843), Anna Suk-Fong Lok, MD (U01-DK082863), Steven H. Belle, PhD, MScHyg (U01-DK082864), Kyong-Mi Chang, MD (U01-DK082866), Michael W. Fried, MD (U01-DK082867), Adrian M. Di Bisceglie, MD (U01-DK082871), William M. Lee, MD (U01-DK082872), Harry L. A. Janssen, MD, PhD (U01-DK082874), Daryl T-Y Lau, MD, MPH (U01-DK082919), Richard K. Sterling, MD, MSc (U01-DK082923), Steven-Huy B. Han, MD (U01-DK082927), Robert C. Carithers, MD (U01-DK082943), Mandana Khalili, MD (U01-DK082944), an interagency agreement with NIDDK: Lilia M. Ganova-Raeva, PhD (A-DK-3002-001) and support from the intramural program, NIDDK, National Institutes of Health (NIH): Marc G. Ghany, MD. Additional funding to support this study was provided to Kyong-Mi Chang, MD, the Immunology Center (NIH/NIDDK Center of Molecular Studies in Digestive and Liver Diseases P30DK50306, NIH Public Health Service Research Grant M01-RR00040), Richard K. Sterling, MD, MSc (UL1TR000058, NCATS (National Center for Advancing Translational Sciences, NIH), Mandana Khalili, MD (CTSA Grant Number UL1TR000004), Michael W. Fried, MD (CTSA Grant Number UL1TR001111), and Anna Suk-Fong Lok ( CTSA Grant Number UL1RR024986 and U54TR001959 .) Additional support was provided by Gilead Sciences, Inc. and Roche Molecular Systems via a Cooperative Research and Development Agreement (CRADA) through the NIDDK.
Publisher Copyright:
© 2023
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - HBV
KW - HBV RNA
KW - HBcrAg
KW - HIV
KW - Serum Biomarkers
UR - http://www.scopus.com/inward/record.url?scp=85125675818&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2021.12.038
DO - 10.1016/j.cgh.2021.12.038
M3 - Article
C2 - 34973459
AN - SCOPUS:85125675818
SN - 1542-3565
VL - 21
SP - 125-135.e8
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 1
ER -