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Publications

Journal Article Epublish

PubMed: 42826017 DOI: 10.1001/jamanetworkopen.2026.37313

Sex Differences in Mortality Among Patients With Hepatocellular Carcinoma.

JAMA Netw Open 9(10):e2637313

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

Affiliations

  • Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California.
  • Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • National Regional Infectious Diseases Center, Clinical Research Center for Infectious Diseases of Shaanxi, Xi'an, China.
  • Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • Center for Metabolic Disorders and Obesity, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • Henry D. Janowitz Division of Gastroenterology, Mount Sinai Health System, New York, New York.
  • Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
  • Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Chiba, Japan.
  • Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, South Korea.
  • Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
  • Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
  • Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
  • Division of Gastroenterology of Hepatology, E-Da Cancer Hospital/I-Shou University, Kaohsiung, Taiwan.
  • Kaiser Permanente Central Hospital, Seattle, Washington.
  • Division of Gastroenterology, University of Washington School of Medicine, Seattle.
  • Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
  • Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas del Instituto Carlos III, Barcelona, Spain.
  • Liver Diseases Group, Vall d'Hebron Research Institute, Barcelona, Spain.
  • San Jose Gastroenterology, San Jose, California.
  • Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
  • Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
  • Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
  • Department of Epidemiology and Population Health, Stanford University, Palo Alto, California.

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.

MeSH

Liver Diseases, Mortality, Carcinoma, Hepatocellular, Liver, Sex Characteristics, Sex, Hepatitis, Sex Differences