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Publications

Journal Article Ppublish

PubMed: 42764626 DOI: 10.1111/jvh.70230

Persistent ALT Elevation and Liver Outcomes After DAA-Induced HCV Cure in People With HIV: Impact of HBV and HDV Co-Infections.

J Viral Hepat 33(10):e70230

Authors: Roberto Rossotti, Alessandro Tavelli, Vincenzo Malagnino, Valentina Svicher, Eugenia Quiros-Roldan, Alessandra Bandera, Francesco Maria Fusco, Marco Rivano Capparuccia, Giovanni Battista Gaeta, Valentina Mazzotta, Massimo Puoti, Antonella d'Arminio Monforte

Affiliations

  • Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
  • Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
  • ICONA Foundation, Milan, Italy.
  • National PhD Programme in One Health Approaches to Infectious Diseases and Life Science Research, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy.
  • Department of Medicine of Systems, University of Rome Tor Vergata, Rome, Italy.
  • Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
  • Department of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili of Brescia, Brescia, Italy.
  • Infectious Disease Unit, Department of Internal Medicine, Fondazione IRCCS Ca, Granda, Ospedale Maggiore Policlinico, Milan, Italy.
  • Department of Pathophysiology and Transplantation, University of Milano, Milan, Italy.
  • UOC Infezioni Sistemiche e dell'Immunodepresso, AORN Ospedali dei Colli, P.O. "D. Cotugno", Naples, Italy.
  • Infectious and Tropical Disease Unit, Policlinico Umberto I, Department of Public Health and Infectious Diseases, Sapienza University, Rome, Italy.
  • Infectious Diseases Unit, University L. Vanvitelli, Naples, Italy.
  • Clinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.
  • School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.

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.

MeSH

Research Design, Coinfection, Liver, Therapeutics, Hepatitis, Viral, Human, Antiviral Agents, Infections, Hepatitis