Sex Differences in Mortality Among Patients With Hepatocellular Carcinoma
Year: 2026
Type: article
Study design: Observational Study
Abstract: Importance: Sex is a well-recognized factor associated with hepatocellular carcinoma (HCC) incidence, but its association with mortality is unclear. Objective: To assess the association between sex and the risk of overall, liver-related, and non-liver-related mortality among patients with HCC. Design, Setting, and Participants: This retrospective cohort study was conducted among patients with HCC in 17 centers from 5 countries and regions (2000-2023). Male and female patients with HCC who had balanced baseline characteristics via inverse probability of treatment weighting (IPTW) were included, with a propensity score-matched cohort included for sensitivity analyses. Data were analyzed between July 10 and September 8, 2025. Exposures: Male vs female sex. Main Outcomes and Measures: Overall, liver-related, and non-liver-related mortality. Results: Among 8594 patients with HCC (mean [SD] age, 63.3 [10.9] years; 6214 male [72.3%]; 5644 Asian [65.7%], 458 Black [5.3%], 615 Hispanic [7.2%], and 1784 White [20.8%]), 4567 were from Asia (53.1%), 6327 had cirrhosis (73.6%), and 6617 had viral etiology (77.0%). In the unmatched cohort, males had a higher overall mortality rate per 100 person-years than females in the total cohort (15.9 [95% CI, 15.3-16.4] vs 13.3 [95% CI, 12.5-14.1]; P < .001) and in Asian (14.1 [95% CI, 13.5-14.7] vs 11.1 [95% CI, 10.3-12.0]; P < .001), Asia region (14.4 [95% CI, 13.6-15.2] vs 10.8 [95% CI, 9.9-11.8]; P < .001), cirrhosis (17.6 [95% CI, 16.9-18.3] vs 14.4 [95% CI, 13.5-15.4]; P < .001), and hepatitis B (13.6 [95% CI, 12.7-14.5] vs 10.0 [95% CI, 8.6-11.5]; P < .001) and C (15.8 [95% CI, 15.0-16.6] vs 13.4 [95% CI, 12.4-14.6]; P < .001) subgroups. In the IPTW-matched cohort, male sex was associated with increased overall mortality in the full cohort (adjusted hazard ratio [aHR], 1.14 [95% CI, 1.05-1.23]; P = .002) and in Asian (aHR, 1.22 [95% CI, 1.10-1.36]; P < .001), Asia region (aHR, 1.23 [95% CI, 1.09-1.39]; P < .001), cirrhosis (aHR, 1.18 [95% CI, 1.08-1.29]; P < .001), and viral (aHR, 1.15 [95% CI, 1.05-1.26]; P = .004) subgroups. Additionally, sex differences varied by liver disease etiology, with male sex having the highest aHR in the association with overall mortality among individuals with alcohol-associated liver disease (aHR, 1.90 [95% CI, 1.02-3.54]; P = .04), followed by those with hepatitis B (aHR, 1.22 [95% CI, 1.01-1.47]; P = .04) or C (aHR, 1.13 [95% CI, 1.02-1.26]; P = .03), but there was no association in patients with metabolic dysfunction-associated steatotic liver disease. There was no significant sex difference for non-liver-related mortality. Conclusions and Relevance: In this study, sex disparities in HCC mortality existed but were heterogeneous across ethnic background and liver disease etiologies. These findings support incorporation of sex-based considerations in HCC management.
Source: JAMA Network Open
Authors: Taotao Yan, Ming-Lun Yeh, Jennifer Leong, Hidenori Toyoda, Hiroshi Abe, Dae Won Jun, Lewis Roberts, Yasuhito Tanaka, Myron Schwartz, Yao-Chun Hsu, Charles Landis, Phillip Vutien, Haruki Uojima, Takashi Honda, Maria Buti, Huy Trinh, Eiichi Ogawa, Satoshi Yasuda, Cheng-Hao Tseng, Mayumi Maeda, Elsa Sola, Takanori Suzuki, Chung-Feng Huang, Pei-Chien Tsai, Chia-Yen Dai, Jee-Fu Huang, Wan-Long Chuang, Ramsey Cheung, Ming-Lung Yu, Mindie H. Nguyen
Institutions: First Affiliated Hospital of Xi'an Jiaotong University, Stanford Medicine, First Hospital of Xi'an, Xi'an Jiaotong University, Kaohsiung Medical University, Kaohsiung Medical University Chung-Ho Memorial Hospital, Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, Ogaki Municipal Hospital, Shinmatsudo Central General Hospital, Hanyang University Seoul Hospital, Hanyang University Medical Center, Hanyang University, Mayo Clinic, Nagoya City University, Kumamoto University, E-Da Hospital, I-Shou University, Kaiser Permanente, University of Washington, Kitasato University, Nagoya University Hospital, Nagoya University, Universitat Autònoma de Barcelona, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Kyushu University, Kyushu University Hospital, VA Palo Alto Health Care System, Stanford University
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,000
OpenAlex ID: W7216553944