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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2025; 31(47): 111637
Published online Dec 21, 2025. doi: 10.3748/wjg.v31.i47.111637
Published online Dec 21, 2025. doi: 10.3748/wjg.v31.i47.111637
Sex-based differences in hepatitis delta virus infection: Insights from the Italian PITER hepatitis delta virus cohort
Barbara Coco, Maurizia R Brunetto, Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa 56123, Tuscany, Italy
Maria Giovanna Quaranta, Maria Elena Tosti, Luigina Ferrigno, Loreta A Kondili, National Center for Global Health, Istituto Superiore di Sanità, Rome 00161, Lazio, Italy
Giuseppina Brancaccio, Infectious Diseases, Department of Life Sciences, Health and Health Professions, Link Campus University, Rome 00165, Lazio, Italy
Alessia Ciancio, Department of Medical Sciences, University of Turin, Turin 10100, Piemonte, Italy
Carmine Coppola, Department of Hepatology, Gragnano Hospital, Gragnano 80054, Campania, Italy
Vincenzo Messina, Department of Infectious Diseases, Sant’Anna Hospital, Caserta 81100, Campania, Italy
Ivan Gentile, Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Campania, Italy
Ernesto Claar, Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Campania, Italy
Filomena Morisco, Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples Federico II, Naples 80131, Campania, Italy
Teresa Santantonio, Department of Clinical and Experimental Medicine, Infectious Diseases, Infectious Diseases University of Foggia, Foggia 71100, Puglia, Italy
Mauro Viganò, Gastroenterology Hepatology and Transplantation Division, ASST Papa Giovanni XXIII, Bergamo 24127, Lombardy, Italy
Irene Cacciola, Department of Internal Medicine, University Hospital of Messina, Cacciola, Messina 98122, Sicily, Italy
Maurizio Pompili, Internal Medicine and Liver Transplantation Unit, Catholic University of Sacred Heart, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
Maurizio Pompili, Translational Medicine and Surgery Department, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario Gemelli IRCCS, Rome 00168, Italy
Francesco Paolo Russo, Department of Surgery Oncology and Gastroenterology, University of Padua, Padua 35128, Veneto, Italy
Antonio Izzi, Department of Infectious Disease and Emergency Infectious Diseases, D. Cotugno Hospital, Naples 80131, Campania, Italy
Grazia A Niro, Department of Gastroenterology, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo 71013, Puglia, Italy
Nicola Coppola, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Naples, 80138, Campania, Italy
Alessandro Soria, Clinic of Infectious Diseases, Fondazione IRCCS San Gerardo dei Tintori, Monza 20900, Lombardy, Italy
Alessandro Federico, Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples 80138, Campania, Italy
Giulia Morsica, Department of Infectious Diseases, San Raffaele Hospital, Milan 20127, Lombardy, Italy
Massimo Puoti, Infectious Disease Unit, Niguarda Hospital, Milan 20162, Lombardy, Italy
Erica Villa, Department of Gastroenterology, University of Modena and Reggio Emilia, Modena 41124, Emilia-Romagna, Italy
Pietro Lampertico, Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granada Ospedale Maggiore Policlinico, Milan 20122, Lombardy, Italy
Giovanni Battista Gaeta, Infectious Disease, University of Campania Luigi Vanvitelli, Naples 80131, Campania, Italy
Loreta A Kondili, Department of Internal Medicine, UniCamillus-Saint Camillus International University of Health Sciences, Rome 00131, Lazio, Italy
Maurizia R Brunetto, Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56125, Tuscany, Italy
PITER Collaborating Investigators, Istituto Superiore di Sanità, Rome 00161, Lazio, Italy
Co-first authors: Barbara Coco and Maria Giovanna Quaranta.
Author contributions: Kondili LA, Brunetto MR, Coco B, Quaranta MG, and Gaeta GB conceptualized the study and prepared the original draft; Quaranta MG, Tosti ME and Ferrigno L performed the formal analysis and investigation; Villa E, Brancaccio G, Ciancio A, Coppola C, Messina V, Gentile I, Claar E, Morisco F, Santantonio T, Viganò M, Cacciola I, Pompili M, Russo FP, Izzi A, Niro GA, Coppola N, Soria A, Federico A, Morsica G, Puoti M and Lampertico P contributed to review and editing; Kondili LA, and Villa E acquired funding; Coco B, Brancaccio G, Ciancio A, Coppola C, Messina V, Gentile I, Claar E, Morisco F, Santantonio T, Viganò M, Cacciola I, Pompili M, Russo FP, Izzi A, Niro GA, Coppola N, Soria A, Federico A, Morsica G, Puoti M, Lampertico P, Brunetto MR and the PITER Collaborating Investigators provided resources; Kondili LA supervised the project; all authors read and approved the final manuscript.
Supported by the Investigator Sponsored Research Grant from Gilead Sciences, No. IN-IT-980-6816; and the Fondazione Italiana per la Ricerca sul Cancro (AIRC), No. IG 2020 ID 24858.
Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki and the principles of Good Clinical Practice. The study protocol was approved on 24 July 2019 by the National Ethical Committee of the Istituto Superiore di Sanità (CEN), as well as by the Ethics Committees of all participating centres. Patient data were evaluated through pseudonymous analysis using codes generated by electronic case report forms. Compliance with applicable data protection regulations, including the EU General Data Protection Regulation, was confirmed by the Data Protection Officer of the Istituto Superiore di Sanità.
Informed consent statement: All patients provided written informed consent to participate in the study.
Conflict-of-interest statement: These authors disclose the following: Kondili LA has received research grant from Gilead Sciences; Brunetto MR has served as advisory board member for AbbVie, Gilead Sciences, Janssen, Roche and speaker for AbbVie, Gilead Sciences, EISAI-MSD; Quaranta MG has received research grant from Gilead Sciences; Gentile I has received consultant honoraria from MSD, AbbVie, Gilead Sciences, Pfizer, GSK, Astrazeneca, Basilea, SOBI, Nordic/Infecto Pharm, Angelini, Moderna, Shionogi, Advanz Pharma, Abbottand Mundipharma Pharmaceuticals as well as has received departmental grants from Gilead Sciences and Advanz Pharma; Santantonio TA has received speaker honorarium and travel support from Gilead Sciences and Abbvie; Viganò M has served as Advisory Board/Speaker Bureau for Gilead Sciences, AbbVie, Kedrion, IPSEN; Soria A has received speaker honorarium, travel support and research funding from AbbVie and Gilead Sciences; Puoti M has received Abbvie, GSK, Gilead Sciences, Pfizer travel grants, speaker in own events; Lampertico P has served as Advisory Board/Speaker Bureau for Roche Pharma/Diagnostics, Gilead Sciences, GSK, AbbVie, Janssen, Myr, Eiger, Antios, Aligos, Vir, Grifols, Altona, Roboscreen; Coco B, Tosti ME, Ferrigno L, Brancaccio G, Ciancio A, Coppola C, Messina V, Claar E, Morisco F, Cacciola I, Pompili M, Russo FP, Izzi A, Niro GA, Coppola N, Alessandro F, Giulia M, Villa E, Gaeta GB and PITER Collaborating Investigators declare that they have no conflict of interest regarding this manuscript.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: By protocol, the property of the data is of participating clinical centers while Istituto Superiore di Sanità acts as coordinating center for data management and analysis. Cumulative data are reported within the paper whereas each patient data is not fully available and without restrictions for ethical reasons. Dr. Kondili (loreta.kondili@iss.it) is in charge for data management and the readers may contact her for specific data request. She will provide the necessary ethical clearances for access to data.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Loreta A Kondili, MD, Professor, National Center for Global Health, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Lazio, Italy.
Received: July 7, 2025
Revised: July 30, 2025
Accepted: November 7, 2025
Published online: December 21, 2025
Processing time: 167 Days and 22.3 Hours
Revised: July 30, 2025
Accepted: November 7, 2025
Published online: December 21, 2025
Processing time: 167 Days and 22.3 Hours
Core Tip
Core Tip: This multi-centre study analyzed 513 patients with chronic hepatitis delta virus (HDV) infection, enrolled across 58 Italian liver clinics regardless of treatment eligibility. The study population reflects the current HDV epidemiology in Italy, including a high proportion of migrant women. Key sex-based differences emerged: Men had a greater burden of metabolic comorbidities and hepatocellular carcinoma, while women, particularly those born abroad, were more likely to develop cirrhosis not only after menopause, as seen in other chronic viral liver diseases, but also at significantly young ages, including those younger than 40 years of age. Tailored care for young migrant women, unvaccinated against hepatitis B virus, and cofactor-guided management for men may improve liver disease outcomes.