Abstract
ABSTRACT
HBV replication is commonly suppressed by HCV, and eradication of HCV with direct‐acting antivirals (DAAs) may favour HBV reactivation. Data on long‐term hepatic outcomes after HCV clearance in people living with HIV (PLWH) with triple viral infections are limited. We analysed all HIV/HCV co‐infected participants in the ICONA and HepaICONA cohorts with complete HBV serology who achieved a sustained virological response (SVR) after DAA therapy. Participants were classified as HIV/HCV, HIV/HCV with isolated anti‐HBc positivity (IHBc), or HIV/HCV/HBV, with HDV testing when available. The outcomes included ALT normalisation, hepatitis flares, and two composite clinical endpoints: CO1 (HCC, hepatic decompensation, liver transplantation, or death) and CO2 (the same plus FIB‐4 progression > 3.25 in non‐cirrhotics). Among 1182 PLWH, 478 had HIV/HCV, 651 had HIV/HCV + IHBc, and 53 had HIV/HCV/HBV co‐infection; six were HDV RNA‐positive. The prevalence of triple co‐infection was 16.6% among HCV‐viraemic participants. Triple co‐infection reduced the likelihood of ALT normalisation (aHR 0.66, 95% CI: 0.45, 0.97); this effect was related to active HDV replication (aHR 0.39, 95% CI: 0.16, 0.94). Over 5213 person‐years, 26 hepatitis flares occurred (IR 0.50/100 PYFU), with only one confirmed HBV reactivation (IR 0.25/100 PYFU). Neither triple nor quadruple infection predicted severe liver events. In PLWH, HCV/HBV co‐infection is relatively common but does not appear to increase hepatic morbidity after HCV cure under tenofovir‐based ART. Persistent ALT elevation after DAA therapy is mainly driven by replicating HDV, supporting routine HDV testing and timely antiviral management in this population.