Predictors of liver disease progression in people living with HIV-HBV co-infection on antiretroviral therapyResearch in context
Kasha P. Singh,
Anchalee Avihingsanon,
Jennifer M. Zerbato,
Wei Zhao,
Sabine Braat,
Surekha Tennakoon,
Ajantha Rhodes,
Gail V. Matthews,
Christopher K. Fairley,
Joe Sasadeusz,
Megan Crane,
Jennifer Audsley,
Sharon R. Lewin
Affiliations
Kasha P. Singh
Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia; Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Victoria, 3004, Australia; Corresponding author. Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia.
Anchalee Avihingsanon
HIV-NAT, Thai Red Cross AIDS Research Center (TRCARC), Bangkok, 10330, Thailand
Jennifer M. Zerbato
Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia
Wei Zhao
Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia
Sabine Braat
Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, 3053, Australia; MISCH (Methods and Implementation Support for Clinical Health) research Hub, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia
Surekha Tennakoon
Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia
Ajantha Rhodes
Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia
Gail V. Matthews
Kirby Institute, UNSW, Kensington, New South Wales, 2052, Australia
Christopher K. Fairley
Melbourne Sexual Health Centre, Alfred Health, Carlton, 3053, Australia
Joe Sasadeusz
Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia; Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Victoria, 3004, Australia
Megan Crane
Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia
Jennifer Audsley
Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia
Sharon R. Lewin
Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia; Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Victoria, 3004, Australia; Corresponding authors. Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia.
Summary: Background: In people living with HIV-HBV, liver fibrosis progression can occur even with suppressive antiretroviral therapy (ART). We investigated the relationship between liver fibrosis and biomarkers of inflammation, apoptosis, and microbial translocation. Methods: In this observational cohort study adults living with HIV-HBV already on effective ART were recruited in Australia and Thailand and followed for 3 years including 6 monthly clinical review and blood tests and annual transient elastography. Differences in clinical and laboratory predictors of liver fibrosis progression were tested followed by regression analysis adjusted for CD4+ T-cells at study entry. A linear mixed model was fitted to longitudinal data to explore changes over time. Findings: 67 participants (85% male, median age 49 y) were followed for 175 person-years. Median duration of ART was 10 years (interquartile range (IQR) 8–16 years). We found 11/59 (19%) participants during 3-years follow-up (6/100 person-years) met the primary endpoint of liver disease progression, defined as increased Metavir stage from baseline to final scan. In regression analysis, progressors compared to non-progressors had higher levels of high mobility group box 1 protein (HGMB1), (median (IQR) 3.7 (2.6–5.0) and 2.4 ng/mL (1.5–3.4) respectively, adjusted relative risk 1.47, 95% CI [1.00, 2.17]) and lower nadir CD4+ T-cell percentage (median 4% (IQR 2–8) and 11% (4–15) respectively (relative risk 0.93, 95% CI [0.88, 0.98]). Interpretation: Progression in liver fibrosis occurs in people with HIV-HBV on suppressive ART. Fibrosis progression was associated with higher HMGB1 and lower percentage nadir CD4+ T-cell count, highlighting the importance of early initiation of HBV-active ART. Funding: This work was supported by NHMRC project grant 1101836; NHMRC practitioner fellowship 1138581 and NHMRC program grant 1149990. The funder had no role in study design, data collection, data analysis, interpretation, writing of this manuscript or decision to submit for publication.
