Sex-based differences in hepatitis delta virus infection: Insights from the Italian PITER hepatitis delta virus cohort.
| Title: | Sex-based differences in hepatitis delta virus infection: Insights from the Italian PITER hepatitis delta virus cohort. |
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| Authors: | Coco B; 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.; Quaranta MG; National Center for Global Health, Istituto Superiore di Sanità, Rome 00161, Lazio, Italy.; Tosti ME; National Center for Global Health, Istituto Superiore di Sanità, Rome 00161, Lazio, Italy.; Ferrigno L; National Center for Global Health, Istituto Superiore di Sanità, Rome 00161, Lazio, Italy.; Brancaccio G; Infectious Diseases, Department of Life Sciences, Health and Health Professions, Link Campus University, Rome 00165, Lazio, Italy.; Ciancio A; Department of Medical Sciences, University of Turin, Turin 10100, Piemonte, Italy.; Coppola C; Department of Hepatology, Gragnano Hospital, Gragnano 80054, Campania, Italy.; Messina V; Department of Infectious Diseases, Sant'Anna Hospital, Caserta 81100, Campania, Italy.; Gentile I; Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Campania, Italy.; Claar E; Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Campania, Italy.; Morisco F; Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples Federico II, Naples 80131, Campania, Italy.; Santantonio T; Department of Clinical and Experimental Medicine, Infectious Diseases, Infectious Diseases University of Foggia, Foggia 71100, Puglia, Italy.; Viganò M; Gastroenterology Hepatology and Transplantation Division, ASST Papa Giovanni XXIII, Bergamo 24127, Lombardy, Italy.; Cacciola I; Department of Internal Medicine, University Hospital of Messina, Cacciola, Messina 98122, Sicily, Italy.; Pompili M; Internal Medicine and Liver Transplantation Unit, Catholic University of Sacred Heart, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy.; Translational Medicine and Surgery Department, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario Gemelli IRCCS, Rome 00168, Italy.; Russo FP; Department of Surgery Oncology and Gastroenterology, University of Padua, Padua 35128, Veneto, Italy.; Izzi A; Department of Infectious Disease and Emergency Infectious Diseases, D. Cotugno Hospital, Naples 80131, Campania, Italy.; Niro GA; Department of Gastroenterology, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo 71013, Puglia, Italy.; Coppola N; Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Naples, 80138, Campania, Italy.; Soria A; Clinic of Infectious Diseases, Fondazione IRCCS San Gerardo dei Tintori, Monza 20900, Lombardy, Italy.; Federico A; Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples 80138, Campania, Italy.; Morsica G; Department of Infectious Diseases, San Raffaele Hospital, Milan 20127, Lombardy, Italy.; Puoti M; Infectious Disease Unit, Niguarda Hospital, Milan 20162, Lombardy, Italy.; Villa E; Department of Gastroenterology, University of Modena and Reggio Emilia, Modena 41124, Emilia-Romagna, Italy.; Lampertico P; Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Lombardy, Italy.; Gaeta GB; Infectious Disease, University of Campania Luigi Vanvitelli, Naples 80131, Campania, Italy.; Kondili LA; National Center for Global Health, Istituto Superiore di Sanità, Rome 00161, Lazio, Italy.; Department of Internal Medicine, UniCamillus-Saint Camillus International University of Health Sciences, Rome 00131, Lazio, Italy. loreta.kondili@iss.it.; Brunetto MR; 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.; Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56125, Tuscany, Italy. |
| Corporate Authors: | PITER Collaborating Investigators |
| Source: | World journal of gastroenterology [World J Gastroenterol] 2025 Dec 21; Vol. 31 (47), pp. 111637. |
| Publication Type: | Journal Article; Multicenter Study |
| Language: | English |
| Journal Info: | Publisher: Baishideng Publishing Group Country of Publication: United States NLM ID: 100883448 Publication Model: Print Cited Medium: Internet ISSN: 2219-2840 (Electronic) Linking ISSN: 10079327 NLM ISO Abbreviation: World J Gastroenterol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2014- : Pleasanton, CA : Baishideng Publishing Group; Original Publication: Beijing : WJG Press, c1998- |
| MeSH Terms: | Liver Cirrhosis*/epidemiology ; Liver Cirrhosis*/virology ; Hepatitis Delta Virus*/isolation & purification ; Hepatitis Delta Virus*/immunology ; Carcinoma, Hepatocellular*/epidemiology ; Carcinoma, Hepatocellular*/virology ; Hepatitis D, Chronic*/epidemiology ; Hepatitis D, Chronic*/virology ; Hepatitis D, Chronic*/complications ; Liver Neoplasms*/epidemiology ; Liver Neoplasms*/virology; Italy/epidemiology ; Coinfection/epidemiology ; Coinfection/virology ; RNA, Viral/blood ; Hepatitis B Surface Antigens/blood ; Humans ; Male ; Female ; Middle Aged ; Sex Factors ; Adult ; Aged ; Risk Factors ; Propensity Score |
| Abstract: | Background: Hepatitis delta virus (HDV) infection is the most severe form of chronic viral hepatitis, yet sex-based clinical differences remain poorly defined. Understanding these differences may inform disease management and guide research.; Aim: To investigate sex-related differences in demographic and clinical characteristics of patients with chronic HDV infection in a nationwide, real-world Italian setting.; Methods: We analyzed demographic, clinical, and virological data from 513 hepatitis B surface antigen/anti-HDV-positive patients, consecutively enrolled between 2019 and 2024, across 58 liver clinics in the Italian PITER HDV cohort. A propensity score-weighted logistic regression model evaluated the association between sex and cirrhosis and/or hepatocellular carcinoma.; Results: Among 513 patients (61.6% male), median age (56.0 years) and age distribution were similar by sex (P = 0.41). Cirrhosis was frequent: 73.4% vs 66.0% (anti-HDV-positive) and 77.8% vs 74.2% (HDV RNA-positive) in males and females, respectively. HDV RNA levels were comparable (P = 0.93). The highest proportion of females with cirrhosis (33.8%) was in the 56-60-year group, similar to males (34.9%). Among patients with cirrhosis aged ≤ 40 years, females, (80.9% of whom of non-Italian origin), were more represented than males (16.1% vs 6.5% respectively, P < 0.05). Male sex was associated with cirrhosis (odds ratio = 1.85; 95% confidence interval: 1.004-3.40). Among HDV RNA-positive patients, males more often had hepatocellular carcinoma, elevated gamma-glutamyl transpeptidase, alcohol use, diabetes, hypertension, steatotic liver disease, and hepatitis C virus/human immunodeficiency virus coinfection. Interferon eligibility was similar.; Conclusion: HDV-infected females develop cirrhosis earlier, without liver disease cofactors, while males show advanced liver disease with multiple cofactors. Tailored care for young migrant women and cofactor-guided management for men may improve HDV outcomes, promoting equity.; (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.) |
| Competing Interests: | 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. |
| Contributed Indexing: | Investigator: A Aghemo, IRCCS Humanitas Research Hospital IRCCS, Rozzano, Italy.; C Asero, University Hospital of Messina, Messina, Italy.; S Babudieri, University of Sassari, Sassari, Italy.; C Baiguera, Niguarda Hospital, Milan, Italy.; L Baiocchi, University of Tor Vergata, Rome, Italy.; F Barbaro, University Hospital of Padua, Padua, Italy.; F Barchiesi, Polytechnic University of Marche, Ancona, Italy.; M Bassetti, Università degli Studi di Genova, Policlinico S. Martino IRCCS, Genova, Italy.; G Bertino, University of Catania, Catania, Italy.; C Bertoni, IRCCS Ospedale San Raffaele and Università Vita-Salute San Raffaele, Milan, Italy.; E Biliotti, Lazzaro Spallanzani-IRCCS, Rome, Italy.; L Bonaffini, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.; C Boni, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.; E Bracciamà, University of Palermo, Palermo, Italy.; L Calza, Alma Mater Studiorum Bologna University, Italy.; N Capoluongo, Ospedali dei Colli, P.O.D. Cotugno, Naples, Italy.; A Castellaccio, Santa Maria Annunziata Hospital, Florence, Italy.; L Cavalletto, University of Padova, Padova University-Hospital, Padova, Italy.; G Cenderello, ASL-1 Imperiese, Sanremo.; L Chemello, University of Padova, Padova University-Hospital, Padova, Italy.; L Chessa, University Hospital, Monserrato, Cagliari, Italy.; L Chidichimo, SS Annunziata Hospital, Cosenza, Italy.; F Conti, Hospital of Faenza, A.U.S.L. of Romagna, Italy.; R Corsini, Azienda Unità Sanitaria Locale, IRCCS di Reggio Emilia, Reggio Emilia, Italy.; C Cosentino, University of Campania Luigi Vanvitelli, Naples, Italy.; V Cossiga, University of Naples, Federico II, Naples, Italy.; R Cotugno, Fondazione IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.; G D'Offizi, Lazzaro Spallanzani-IRCCS, Rome, Italy.; M Dallio, University of Campania Luigi Vanvitelli, Naples, Italy.; V Di Marco, University of Palermo, Palermo, Italy.; E Falbo, Azienda Sanitaria Provinciale CZ-Distretto del Lametino, Lamezia Terme (CZ.; N Forni, ASL-1 Imperiese, Sanremo.; FG Foschi, Hospital of Faenza, A.U.S.L. of Romagna, Italy.; D Ieluzzi, University Hospital of Verona, Verona, Italy.; D Laccabue, Università degli Studi di Parma, Parma, Italy.; A Loglio, Papa Giovanni XXIII Hospital, Bergamo, Italy.; F Longobardi, Gragnano Hospital, Gragnano (NA.; S Madonia, Villa Sofia-Cervello Hospital, Palermo, Italy.; I Maida, University of Sassari, Sassari, Italy.; M Marracci, Polytechnic University of Marche, Ancona, Italy.; A Marrone, University of Campania Luigi Vanvitelli, Naples, Italy.; A Mastroianni, SS Annunziata Hospital, Cosenza, Italy.; B Mattioli, Istituto Superiore di Sanità, Rome, Italy.; R Meli, IRCCS Humanitas Research Hospital IRCCS, Rozzano, Italy.; M Michele, University Hospital Policlinico, Bari, Italy.; G Nardone, University of Naples Federico II, Naples, Italy.; A Pan, Azienda Socio-Sanitaria Territoriale di Cremona, Cremona, Italy.; N Passigato, University Hospital Borgo Trento, Verona, Italy.; A Pellicelli, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy.; P Pierotti, Santa Maria Annunziata Hospital, Florence, Italy.; B Pinchera, University of Naples Federico II, Naples, Italy.; F Ponziani, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy.; C Porcu, University Hospital, Monserrato, Cagliari, Italy.; A Risicato, University of Catania, Catania, Italy.; A Rocco, University of Naples Federico II, Naples, Italy.; V Rosato, Betania Hospital, Naples, Italy.; E Salsi, Azienda Unità Sanitaria Locale, IRCCS di Reggio Emilia, Reggio Emilia, Italy.; E Settimo, University of Bari, Bari, Italy.; G Stornaiuolo, University of Campania 'Luigi Vanvitelli', Naples, Italy.; L Surace, Azienda Sanitaria Provinciale CZ-Distretto del Lametino, Lamezia Terme (CZ.; P Toniutto, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy.; P Zanaga, University of Padua, Padua, Italy.; AL Zignego, University of Florence, Italy.; Keywords: Chronic hepatitis delta virus infection; Cirrhosis; Hepatitis delta virus; Migrant; Sex differences |
| Substance Nomenclature: | 0 (RNA, Viral); 0 (Hepatitis B Surface Antigens) |
| Entry Date(s): | Date Created: 20260102 Date Completed: 20260319 Latest Revision: 20260319 |
| Update Code: | 20260320 |
| PubMed Central ID: | PMC12754152 |
| DOI: | 10.3748/wjg.v31.i47.111637 |
| PMID: | 41479753 |
| Database: | MEDLINE |
Journal Article; Multicenter Study