Sex-based disparities in liver transplantation: Evidence from a nationwide Italian cohort

Chiara Becchetti; Silvia Trapani; Lucia Masiero; Silvia Testa; Francesca D'Arcangelo; Lucia Lapenna; Manuela Merli; Valentina Cossiga; Maria Guarino; Filomena Morisco; Marta Cilla; Federica Invernizzi; Elisabetta Cerutti; Pierluigi Toniutto; Francesca Puoti; Massimo Cardillo; Giuseppe Feltrin; Patrizia Burra; Special Interest Group (SIG) Gender in Hepatology of the Associazione Italiana Studio del Fegato (AISF)

doi:10.1016/j.jhepr.2025.101387

Sex-based disparities in liver transplantation: Evidence from a nationwide Italian cohort

JHEP Rep. 2025 Mar 7;7(6):101387. doi: 10.1016/j.jhepr.2025.101387. eCollection 2025 Jun.

Authors

Chiara Becchetti¹, Silvia Trapani², Lucia Masiero², Silvia Testa², Francesca D'Arcangelo³, Lucia Lapenna⁴, Manuela Merli⁴, Valentina Cossiga⁵, Maria Guarino⁵, Filomena Morisco⁵, Marta Cilla⁶, Federica Invernizzi⁶, Elisabetta Cerutti⁷, Pierluigi Toniutto⁸, Francesca Puoti², Massimo Cardillo⁹, Giuseppe Feltrin², Patrizia Burra³; Special Interest Group (SIG) Gender in Hepatology of the Associazione Italiana Studio del Fegato (AISF)

Affiliations

¹ Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
² Italian National Transplant Center, National Institute of Health, Rome, Italy.
³ Gastroenterology, Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy.
⁴ Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
⁵ Department of Clinical Medicine and Surgery, Diseases of the Liver and Biliary System Unit, University of Naples Federico II, Naples, Italy.
⁶ Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, Milan, Italy.
⁷ Department of Anesthesia, Transplant and Surgical Intensive Care, Azienda Ospedaliera Universitaria delle Marche, Ancona, Italy.
⁸ Hepatology and Liver Transplantation Unit, Department of Medicine, University of Udine, Udine, Italy.
⁹ Fondazione IRCSS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.

Abstract

Background & aims: Although sex-based disparities in the liver transplantation (LT) setting have been acknowledged for several years, particularly by studies conducted in the USA, data from European countries are scarce.

Methods: We conducted a nationwide, retrospective, observational study on candidates identified for LT in Italy between January 2017 and December 2021 using national registry data with follow-up until June 2023. The primary aim was to assess sex-based differences in LT access, analyzing delisting, retransplantation, and mortality rates. Patients were monitored from waitlist admission to transplant, removal, or death, with competing risks modeled (Fine and Gray) multivariable analysis. Survival outcomes were evaluated using Kaplan-Meier estimates, time-dependent Cox models, and stratified log-rank tests.

Results: In total, 7,563 patients were included in the analysis, 5,575 (73.7%) of whom were men. Men had higher 1- and 2-year probabilities of undergoing LT compared with women for both liver cirrhosis (subdistribution hazard ratio [sHR] 1.13, 95% CI 1.02-1.26, p = 0.02 and sHR 1.12, 95% CI 1.01-1.24, p = 0.03, respectively) and hepatocellular carcinoma (HCC) (sHR 1.20, 95% CI 1.07-1.36, p = 0.003 and sHR 1.21, 95% CI 1.08-1.35, p = 0.001, respectively). The wait list (WL) dropout rate in men did not differ significantly to that for women (12.6% vs. 13.9%, p = 0.14) except when the indication to LT was HCC (10.6% vs. 14.2%, p = 0.035). In addition, men had a lower wait list (WL) mortality rate compared with women (7.0% vs. 8.5%, p = 0.04). Post-LT survival rates were similar for both sexes.

Conclusions: In this large Italian cohort, female standard allocation patients appeared to be at a disadvantage compared with men, because they received LT less frequently, but with similar post-LT outcomes.

Impact and implications: Although sex-based disparities in the LT setting have been acknowledged for several years, particularly in studies conducted in the USA, few data are available in Europe. Our study provides an exhaustive overview regarding the disadvantage facing women outside the USA in accessing LT. By detailing these differences, it provides solid arguments for developing equitable health policy. Given that these differences are affected by the national scenario, having local data is crucial for defining possible targeted actions.

Keywords: Equity; Gender; Liver cirrhosis; Liver transplant.