Women With Alcohol-Related Liver Disease Face Greater Risk of Mortality Than Men

Findings from a recent study published in the Journal of Hepatology are calling attention to sex-based differences in the prevalence of prognosis of steatotic liver disease (SLD) phenotypes.¹

Results showed although all forms of SLD were about twice as common in male participants compared to their female counterparts, the risk of alcohol-related liver disease (ALD) as well as metabolic dysfunction-associated and alcohol-related liver disease (MetALD)-associated mortality was significantly greater in women.¹

Published in 2023, results from a modified Delphi process was led by 3 large pan-national liver associations prompted a change from the previous nonalcoholic fatty liver disease (NAFLD) nomenclature to more accurately reflect the manifestations of SLD and how they may arise from distinct or coexisting etioligies. Since the implementation of this revised nomenclature, little research has explored sex-based differences in the prevalence of prognosis of SLD based on the new terms metabolic dysfunction-associated steatotic liver disease (MASLD), ALD, and MetALD.²

“Steatotic liver disease is a major and increasingly prevalent condition that is likely an underlying precursor to many conditions, including those involving the heart,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology in the Smidt Heart Institute at Cedars-Sinai, in a press release.³ “We are paying even more attention to steatotic liver disease because we are seeing how it tracks closely with established cardiovascular risk factors such as hypertension, high cholesterol and diabetes.”

To assess sex-based differences in the prevalence and prognosis of updated SLD phenotypes, investigators analyzed representative US data from the National Health and Nutrition Examination Survey (NHANES) III, conducted between 1988-1994 and including standardized ultrasonographic measures of hepatic steatosis, assessment of cardiometabolic risk traits, and questionnaire data on alcohol intake for 31,311 participants.¹

Investigators excluded NHANES III participants < 20 years of age and those who were missing ultrasonography or key covariate data. The remaining 10,007 participants were included in the present analysis and followed for all-cause mortality with National Death Index records through December 31, 2019.¹

The presence of MASLD was defined as steatosis in the presence of any cardiometabolic risk trait. The presence of ALD was defined as steatosis in the presence of consuming >420 g of alcohol/week for males and >350 g/week for females. The presence of MetALD was defined as a distinct group of patients with MASLD who consumed 210-420 g of alcohol/week for males and 140-350 g/week for females.¹

Among the cohort, the mean age was 42 years and 50.3% of participants were female. Based on the revised SLD nomenclature, 1,461 participants were classified as having MASLD, 225 had MetALD, 105 had ALD, 180 had other types of SLD, and 8,036 had no SLD. A total of 2,495 deaths occurred over a median follow-up period of 26.7 years.¹

Investigators noted the prevalence of SLD phenotypes differed significantly between male and female participants. The prevalence of MASLD, MetALD, and ALD was 18.5%, 3.2%, and 1.7%, respectively, in men, while the corresponding prevalence in women was 10.3%, 1.2%, and 0.3% (sex difference P <.001 for all).¹

In multivariable-adjusted survival analyses, MASLD was not significantly associated with all-cause mortality for either sex. However, investigators pointed out MetALD was associated with an 83% greater hazard of all-cause mortality in women (hazard ratio [HR], 1.83; 95% Confidence interval [CI], 1.29-2.57) but was not significantly associated with mortality in males (sex difference P = .005).¹

Although the presence of ALD was significantly associated with all-cause mortality in both sexes, the magnitude was greater in women (HR, 3.49; 95% CI, 1.86-6.52) than men (HR, 1.89; 95% CI, 1.42-2.51; sex difference P = .080).¹

Upon further analysis, when SLD phenotypes were considered in putative order of etiologic severity, the trend across worsening phenotypes was not significant for sex differences in prevalence (P = .88) but was significant for sex differences in mortality risk (P = .019).¹

Investigators pointed out NHANES III was conducted between 1988 and 1994 and recognized the prevalence of metabolic dysfunction and alcohol use may have changed over time. Thus, they suggested additional studies may be needed to validate the current findings and shared their plans to continue to study why the female liver is more affected by alcohol than the male liver and what lifestyle changes might reduce the risk of SLD in female patients.¹

“Because alcohol consumption is modifiable, limiting alcohol intake particularly in women at risk for SLD could be critical as part of efforts to mitigate mortality risk in patients with SLD,” investigators concluded.¹

References:

1. Cheng S, Hongwei J. Sex differences in prevalence and prognosis of steatotic liver disease phenotypes: Biological sex matters. Journal of Hepatology. https://doi.org/10.1016/j.jhep.2023.08.013
2. Cedars-Sinai. Study: Women With Alcohol-Related Liver Disease Have Greater Mortality Risk Than Men With Condition. Newswise. January 25, 2024. Accessed January 29, 2024. https://www.newswise.com/articles/study-women-with-alcohol-related-liver-disease-have-greater-mortality-risk-than-men-with-condition
3. Rinella ME, Lazarus JV, Ratziu V, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Ann Hepatol. 2024;29(1):101133. doi:10.1016/j.aohep.2023.101133