Predictors of liver disease progression in people living with HIV-HBV co-infection on antiretroviral therapy

Background In people living with HIV-HBV, liver fi brosis progression can occur even with suppressive antiretroviral therapy (ART). We investigated the relationship between liver fi brosis and biomarkers of in fl ammation, 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 fi brosis progression were tested followed by regression analysis adjusted for CD4+ T-cells at study entry. A linear mixed model was fi tted 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, de fi ned as increased Metavir stage from baseline to fi nal 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 fi brosis 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.