Differential Mortality Risk by Age in Males and Females With Steatotic Liver Disease

Taotao Yan , Nicholas Chien , Vy H. Nguyen , Isaac Le , Surya Teja Gudapati , Angela Chau , Xinrong Zhang , Scott Barnett , Sovann Linden , Linda Henry , Ramsey Cheung , Mindie H. Nguyen

MedComm ›› 2026, Vol. 7 ›› Issue (4) : e70677

PDF (1236KB)
MedComm ›› 2026, Vol. 7 ›› Issue (4) :e70677 DOI: 10.1002/mco2.70677
ORIGINAL ARTICLE
Differential Mortality Risk by Age in Males and Females With Steatotic Liver Disease
Author information +
History +
PDF (1236KB)

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of premature mortality, but data on sex differences in mortality remain limited. We compared the overall, nonliver-related, and liver-related mortality rates per 1000 person-years in MASLD patients by sex. Propensity score matching (PSM) yielded 3579 pairs of females and males with balanced characteristics from a cohort of 8517 MASLD patients (53.1% female, 46.6% male) seen at Stanford University Medical Center (1995–2023). In the total PSM cohort, the overall (12.68 vs. 12.92), nonliver-related (11.43 vs. 11.60), and liver-related (1.25 vs. 1.32) mortality rates were similar between males and females. However, in age-stratified analyses, females had higher overall (7.99 vs. 4.95, p = 0.02) and nonliver-related (7.20 vs. 4.71, p = 0.05) mortality rates among younger (≤50 years) patients, with opposite direction among the older group with higher overall (21.40 vs. 16.51, p = 0.02) and nonliver-related (19.02 vs. 14.80, p = 0.04) mortality rates in males. In Cox regression analyses, male sex was associated with lower risks of overall and nonliver-related mortality (adjusted hazard ratio [aHR] 0.59 and 0.61) among patients ≤50 years, but with higher risks among those >50 years (aHR 1.32 and 1.30). Sex and age should be considered in the management strategies for people with MASLD.

Keywords

age / liver-related mortality / MASLD / nonliver-related mortality / overall mortality / sex differences

Cite this article

Download citation ▾
Taotao Yan, Nicholas Chien, Vy H. Nguyen, Isaac Le, Surya Teja Gudapati, Angela Chau, Xinrong Zhang, Scott Barnett, Sovann Linden, Linda Henry, Ramsey Cheung, Mindie H. Nguyen. Differential Mortality Risk by Age in Males and Females With Steatotic Liver Disease. MedComm, 2026, 7 (4) : e70677 DOI:10.1002/mco2.70677

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

M. H. Le, D. M. Le, T. C. Baez, et al., “Global Incidence of Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis of 63 Studies and 1,201,807 Persons,” Journal of Hepatology 79, no. 2 (2023): 287–295.

[2]

T. G. Simon, B. Roelstraete, H. Khalili, H. Hagstrom, and J. F. Ludvigsson, “Mortality in Biopsy-confirmed Nonalcoholic Fatty Liver Disease: Results From a Nationwide Cohort,” Gut 70, no. 7 (2021): 1375–1382.

[3]

K. S. Kim, S. Hong, H. Y. Ahn, and C. Y. Park, “Metabolic Dysfunction-Associated Fatty Liver Disease and Mortality: A Population-Based Cohort Study,” Diabetes Metab J 47, no. 2 (2023): 220–231.

[4]

R. Marcos, C. Correia-Gomes, H. Miranda, and F. Carneiro, “Liver Gender Dimorphism–insights From Quantitative Morphology,” Histology and Histopathology 30, no. 12 (2015): 1431–1437.

[5]

A. G. Singal, J. M. Llovet, M. Yarchoan, et al., “AASLD Practice Guidance on Prevention, Diagnosis, and Treatment of Hepatocellular Carcinoma,” Hepatology 78, no. 6 (2023): 1922–1965.

[6]

A. Chau, M. L. Yeh, P. C. Tsai, et al., “Sex Differences in Treatment Response to Nucleos(t)Ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study,” Clinical Gastroenterology and Hepatology 22, no. 3 (2024): 572–580, e5.

[7]

Y. C. Hwang, H. Y. Ahn, S. W. Park, and C. Y. Park, “Nonalcoholic Fatty Liver Disease Associates with Increased Overall Mortality and Death from Cancer, Cardiovascular Disease, and Liver Disease in Women but Not Men,” Clinical Gastroenterology and Hepatology 16, no. 7 (2018): 1131–1137, e5.

[8]

C. E. Fu, M. Teng, D. Tung, et al., “Sex and Race-Ethnic Disparities in Metabolic Dysfunction-Associated Steatotic Liver Disease: An Analysis of 40,166 Individuals,” Digestive Diseases and Sciences 69, no. 9 (2024): 3195–3205.

[9]

L. Valenti, S. Pelusi, C. Bianco, et al., “Definition of Healthy Ranges for Alanine Aminotransferase Levels: A 2021 Update,” Hepatol Commun 5, no. 11 (2021): 1824–1832.

[10]

National Library of Medicine: Creatinine blood test, https://medlineplus.gov/ency/article/003475.htm.

[11]

E. B. Gold, “The Timing of the Age at Which Natural Menopause Occurs,” Obstetrics and Gynecology Clinics of North America 38, no. 3 (2011): 425–440.

[12]

T. Alinia, S. Khodakarim, F. R. Tehrani, and S. Sabour, “Age at Natural Menopause; a Data Mining Approach (Data From the National Health and Nutrition Examination Survey 2013–2014),” Int J Prev Med 12 (2021): 180.

[13]

B. N. Sanchez, J. S. Volek, W. J. Kraemer, C. Saenz, and C. M. Maresh, “Sex Differences in Energy Metabolism: A Female-Oriented Discussion,” Sports Medicine (Auckland, NZ) 54, no. 8 (2024): 2033–2057.

[14]

P. Anagnostis and J. C. Stevenson, “Cardiovascular Health and the Menopause, Metabolic Health,” Best Practice & Research Clinical Endocrinology & Metabolism 38, no. 1 (2024): 101781.

[15]

G. D. Mishra, M. C. Davies, S. Hillman, et al., “Optimising Health After Early Menopause,” Lancet 403, no. 10430 (2024): 958–968.

[16]

S. Kundu and S. S. Acharya, “Exploring the Triggers of Premature and Early Menopause in India: A Comprehensive Analysis Based on National Family Health Survey, 2019–2021,” Scientific Reports 14, no. 1 (2024): 3040.

[17]

G. D. Mishra, H. F. Chung, A. Cano, et al., “EMAS Position Statement: Predictors of Premature and Early Natural Menopause,” Maturitas 123 (2019): 82–88.

[18]

T. Burkard, M. Moser, M. Rauch, S. S. Jick, and C. R. Meier, “Utilization Pattern of Hormone Therapy in UK General Practice Between 1996 and 2015: A Descriptive Study,” Menopause 26, no. 7 (2019): 741–749.

[19]

A. Mellemkjaer, M. B. Kjaer, D. Haldrup, H. Gronbaek, and K. L. Thomsen, “Management of Cardiovascular Risk in Patients With Metabolic Dysfunction-associated Steatotic Liver Disease,” Eur J Intern Med 122 (2024): 28–34.

[20]

B. Ricci, E. Cenko, Z. Vasiljevic, et al., “Acute Coronary Syndrome: The Risk to Young Women,” Journal of the American Heart Association 6, no. 12 (2017): e007519.

[21]

E. Cenko, J. Yoon, S. Kedev, et al., “Sex Differences in Outcomes after STEMI: Effect Modification by Treatment Strategy and Age,” JAMA Internal Medicine 178, no. 5 (2018): 632–639.

[22]

J. H. Jeong, Y. G. Kim, K. D. Han, et al., “Association of Fatty Liver Index With Sudden Cardiac Arrest in Young Adults,” Metabolism 158, (2024): 155981.

[23]

S. Wu, Y. Li, Y. Zhang, et al., “Sex and Age Differences in the Association between Metabolic Dysfunction-Associated Fatty Liver Disease and Heart Failure: A Prospective Cohort Study,” Circ Heart Fail 17, no. 2 (2024): e010841.

[24]

R. Ren and Y. Zheng, “Sex Differences in Cardiovascular and All-cause Mortality in Nonalcoholic Fatty Liver Disease in the US Population,” Nutrition, Metabolism and Cardiovascular Diseases 33, no. 7 (2023): 1349–1357.

[25]

T. Yan, X. Zhang, T. Wong, R. Cheung, and M. H. Nguyen, “Sex Differences in Adverse Liver and Nonliver Outcomes in Steatotic Liver Disease,” JAMA Network Open 7, no. 12 (2024): e2448946.

[26]

D. Zhao, Y. Wang, N. D. Wong, and J. Wang, “Impact of Aging on Cardiovascular Diseases: From Chronological Observation to Biological Insights: JACC Family Series,” JACC Asia 4, no. 5 (2024): 345–358.

[27]

S. M. Toth-Manikowski, W. Yang, L. Appel, et al., “Sex Differences in Cardiovascular Outcomes in CKD: Findings from the CRIC Study,” American Journal of Kidney Diseases 78, no. 2 (2021): 200–209, e1.

[28]

G. Issa, Y. Shang, R. Strandberg, H. Hagstrom, and A. Wester, “Cause-specific Mortality in 13,099 Patients With Metabolic Dysfunction-associated Steatotic Liver Disease in Sweden,” Journal of Hepatology 83, no. 3 (2025): 643–651.

[29]

W. Chen, L. Cao, and Z. Wu, “Association between Physical Activity and Prevalence/Mortality of Non-Alcoholic Fatty Liver Disease in Different Socioeconomic Settings,” International Journal of Public Health 68 (2023): 1605031.

[30]

M. E. Rinella, J. V. Lazarus, V. Ratziu, et al., “A Multisociety Delphi Consensus Statement on New Fatty Liver Disease Nomenclature,” Journal of Hepatology 79, no. 6 (2023): 1542–1556.

[31]

European Association for the Study of the Liver. Electronic Address eee, Clinical Practice Guideline P, Chair, Representative EGB, Panel M. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update. Journal of Hepatology 2021; 75(3): 659–689.

[32]

M. E. Rinella, B. A. Neuschwander-Tetri, M. S. Siddiqui, et al., “AASLD Practice Guidance on the Clinical Assessment and Management of Nonalcoholic Fatty Liver Disease,” Hepatology 77, no. 5 (2023): 1797–1835.

[33]

S. Han, M. Choi, B. Lee, et al., “Accuracy of Noninvasive Scoring Systems in Assessing Liver Fibrosis in Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis,” Gut Liver 16, no. 6 (2022): 952–963.

[34]

P. C. Austin, “Optimal Caliper Widths for Propensity-score Matching When Estimating Differences in Means and Differences in Proportions in Observational Studies,” Pharmaceutical Statistics 10, no. 2 (2011): 150–161.

[35]

M. Lunt, “Selecting an Appropriate Caliper Can be Essential for Achieving Good Balance With Propensity Score Matching,” American Journal of Epidemiology 179, no. 2 (2014): 226–235.

[36]

J. G. Connolly and J. J. Gagne, “Comparison of Calipers for Matching on the Disease Risk Score,” American Journal of Epidemiology 183, no. 10 (2016): 937–948.

[37]

H. Lin, T. C. Yip, X. Zhang, et al., “Age and the Relative Importance of Liver-related Deaths in Nonalcoholic Fatty Liver Disease,” Hepatology 77, no. 2 (2023): 573–584.

[38]

V. H. Nguyen, I. Le, A. Ha, et al., “Differences in Liver and Mortality Outcomes of Non-alcoholic Fatty Liver Disease by Race and Ethnicity: A Longitudinal Real-world Study,” Clin Mol Hepatol 29, no. 4 (2023): 1002–1012.

[39]

Q. Feng, C. N. Izzi-Engbeaya, P. Manousou, and M. Woodward, “Fibrosis Status, Extrahepatic Multimorbidity and all-cause Mortality in 53,093 Women and 74,377 Men With Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) in UK biobank,” BMC gastroenterology 25, no. 1 (2025): 546.

[40]

T. J. VanderWeele and P. Ding, “Sensitivity Analysis in Observational Research: Introducing the E-Value,” Annals of internal medicine 167, no. 4 (2017): 268–274.

RIGHTS & PERMISSIONS

2026 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.

PDF (1236KB)

0

Accesses

0

Citation

Detail

Sections
Recommended

/