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.
Sex-based differences in hepatitis delta virus infection: Insights from the Italian PITER hepatitis delta virus cohort / Coco, Barbara; Quaranta, Maria Giovanna; Tosti, Maria Elena; Ferrigno, Luigina; Brancaccio, Giuseppina; Ciancio, Alessia; Coppola, Carmine; Messina, Vincenzo; Gentile, Ivan; Claar, Ernesto; Morisco, Filomena; Santantonio, Teresa; Viganò, Mauro; Cacciola, Irene; Pompili, Maurizio; Russo, Francesco Paolo; Izzi, Antonio; Niro, Grazia A; Coppola, Nicola; Soria, Alessandro; Federico, Alessandro; Morsica, Giulia; Puoti, Massimo; Villa, Erica; Lampertico, Pietro; Gaeta, Giovanni Battista; Kondili, Loreta A; Brunetto, Maurizia R; PITER collaborating investigators (Aghemo, Alessio; Asero, Clelia; Babudieri, Sergio; Baiguera, Chiara; Baiocchi, Leonardo; Barbaro, Francesco; Barchiesi, Francesco; Bassetti, Matteo; Bertino, Gaetano; Bertoni, Costanza; Biliotti, Elisa; Bonaffini, Luca; Boni, Carolina; Bracciamà, Emanuele; Calza, Leonardo; Capoluongo, Nicolina; Castellaccio, Alice; Cavalletto, Luisa; Cenderello, Giovanni; Chemello, Liliana; Chessa, Luchino; Chidichimo, Luciana; Conti, Fabio; Corsini, Romina; Cosentino, Clelia; Cossiga, Valentina; Cotugno, Rosa; D’Offizi, Gianpiero; Dallio, Marcello; Di Marco, Vito; Falbo, Elisabetta; Forni, Nicola; Foschi Francesco, Giuseppe; Ieluzzi, Donatella; Laccabue, Diletta; Loglio, Alessandro; Longobardi, Francesco; Madonia, Salvatore; Maida, Ivana; Marracci, Monia; Marrone, Aldo; Mastroianni, Antonio; Mattioli, Benedetta; Meli, Rossella; Michele, Milella; Nardone, Gerardo; Pan, Angelo; Passigato, Nicola; Pellicelli, Adriano; Pierotti, Piera; Pinchera, Biagio; Ponziani, Francesca; Porcu, Carmen; Risicato, Alfredo; Rocco, Alba; Rosato, Valerio; Salsi, Eleonora; Settimo, Enrica; Stornaiuolo, Gianfranca; Surace, Lorenzo; Toniutto, Pierluigi; Zanaga, Paola; Zignego Anna, Linda). - In: WORLD JOURNAL OF GASTROENTEROLOGY. - ISSN 1007-9327. - 31:47(2025). [10.3748/wjg.v31.i47.111637]
Sex-based differences in hepatitis delta virus infection: Insights from the Italian PITER hepatitis delta virus cohort
Messina, Vincenzo;Federico, Alessandro;Bassetti Matteo;Boni Carolina;Corsini Romina;Laccabue Diletta;
2025-01-01
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.| File | Dimensione | Formato | |
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