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Peer-reviewedCC BY 4.0JAMA Network Open

Sex Differences in Mortality Among Patients With Hepatocellular Carcinoma

  • Taotao Yan1,2,3
  • Ming-Lun Yeh4,5,6
  • Jennifer Leong7
  • Hidenori Toyoda8
  • Hiroshi Abe9
  • Dae Won Jun10
  • Lewis Roberts11
  • Yasuhito Tanaka12,13
  • Myron Schwartz7
  • Yao-Chun Hsu14
  • Charles Landis15
  • Phillip Vutien16
18 more authors
  • Haruki Uojima17
  • Takashi Honda18
  • Maria Buti19,20
  • Huy Trinh21
  • Eiichi Ogawa22
  • Satoshi Yasuda8
  • Cheng-Hao Tseng14
  • Mayumi Maeda1
  • Elsa Sola1
  • Takanori Suzuki23
  • Chung-Feng Huang4,5,6
  • Pei-Chien Tsai4
  • Chia-Yen Dai4,5,6
  • Jee-Fu Huang4,5,6
  • Wan-Long Chuang4,5,6
  • Ramsey Cheung1,24
  • Ming-Lung Yu4,5,6
  • Mindie H. Nguyen1,25
25 affiliations
  1. 1Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
  2. 2Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
  3. 3National Regional Infectious Diseases Center, Clinical Research Center for Infectious Diseases of Shaanxi, Xi’an, China
  4. 4Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
  5. 5Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
  6. 6Center for Metabolic Disorders and Obesity, Kaohsiung Medical University, Kaohsiung, Taiwan
  7. 7Henry D. Janowitz Division of Gastroenterology, Mount Sinai Health System, New York, New York
  8. 8Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
  9. 9Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Chiba, Japan
  10. 10Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, South Korea
  11. 11Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
  12. 12Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
  13. 13Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
  14. 14Division of Gastroenterology of Hepatology, E-Da Cancer Hospital/I-Shou University, Kaohsiung, Taiwan
  15. 15Kaiser Permanente Central Hospital, Seattle, Washington
  16. 16Division of Gastroenterology, University of Washington School of Medicine, Seattle
  17. 17Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
  18. 18Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
  19. 19Liver 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
  20. 20Liver Diseases Group, Vall d’Hebron Research Institute, Barcelona, Spain
  21. 21San Jose Gastroenterology, San Jose, California
  22. 22Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
  23. 23Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
  24. 24Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
  25. 25Department of Epidemiology and Population Health, Stanford University, Palo Alto, California
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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.

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Cite

BibTeXRIS
BibTeX
@article{yan2026differences,
  title = {{Sex Differences in Mortality Among Patients With Hepatocellular Carcinoma}},
  author = {Taotao Yan and Ming-Lun Yeh and Jennifer Leong and Hidenori Toyoda and Hiroshi Abe and Dae Won Jun and Lewis Roberts and Yasuhito Tanaka and Myron Schwartz and Yao-Chun Hsu and Charles Landis and Phillip Vutien and Haruki Uojima and Takashi Honda and Maria Buti and Huy Trinh and Eiichi Ogawa and Satoshi Yasuda and Cheng-Hao Tseng and Mayumi Maeda and Elsa Sola and Takanori Suzuki and Chung-Feng Huang and Pei-Chien Tsai and Chia-Yen Dai and Jee-Fu Huang and Wan-Long Chuang and Ramsey Cheung and Ming-Lung Yu and Mindie H. Nguyen},
  journal = {JAMA Network Open},
  year = {2026},
  month = oct,
  doi = {10.1001/jamanetworkopen.2026.37313},
  url = {https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2854758},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Sex Differences in Mortality Among Patients With Hepatocellular Carcinoma
AU  - Taotao Yan
AU  - Ming-Lun Yeh
AU  - Jennifer Leong
AU  - Hidenori Toyoda
AU  - Hiroshi Abe
AU  - Dae Won Jun
AU  - Lewis Roberts
AU  - Yasuhito Tanaka
AU  - Myron Schwartz
AU  - Yao-Chun Hsu
AU  - Charles Landis
AU  - Phillip Vutien
AU  - Haruki Uojima
AU  - Takashi Honda
AU  - Maria Buti
AU  - Huy Trinh
AU  - Eiichi Ogawa
AU  - Satoshi Yasuda
AU  - Cheng-Hao Tseng
AU  - Mayumi Maeda
AU  - Elsa Sola
AU  - Takanori Suzuki
AU  - Chung-Feng Huang
AU  - Pei-Chien Tsai
AU  - Chia-Yen Dai
AU  - Jee-Fu Huang
AU  - Wan-Long Chuang
AU  - Ramsey Cheung
AU  - Ming-Lung Yu
AU  - Mindie H. Nguyen
PY  - 2026
DA  - 2026/10/02
JO  - JAMA Network Open
DO  - 10.1001/jamanetworkopen.2026.37313
UR  - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2854758
AB  - 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.
SN  - 2574-3805
ER  -