Study Finds Sex Differences in MASLD Adverse Events: Cirrhosis Greater Risk in Women

Taotao Yan, MD, PhD

Credit: Stanford Medicine

A recent study found women with metabolic dysfunction-associated steatotic liver disease (MASLD) had a greater incidence of cirrhosis and liver adverse events, while men had a greater risk of hepatic decompensation, hepatocellular carcinoma, cardiovascular diseases (CVD), chronic kidney disease, and non-sex specific cancers.¹

MASLD, affecting approximately 30% of the global population with a growing prevalence, is the leading cause of liver and non-liver adverse events.² Investigators sought to examine the sex differences of these adverse events, both liver and non-liver-related.¹

“To our knowledge, this is the first and largest cohort study specifically designed to examine the association of sex with adverse clinical outcomes of MASLD,” wrote investigators, led by Taotao Yan, MD, PhD, from division of gastroenterology and hepatology at Stanford University Medical Center and the department of infectious diseases at The First Affiliated Hospital of Xi’an Jiaotong University in China.

Adult participants with MASLD (n = 761,403), pulled from the 2007 to 2022 Merative MarketScan Research Database, were propensity scores matched with the opposite sex based on baseline characteristics. The study included 344,436 pairs of matched males and females. The mean age was 52.7 and 53 years for males and females, respectively.

Among male and female participants, 16.9% and 16.8% had obesity, 33.2% and 33.3% had diabetes, 52.6% and 62.3% had hypertension, 47.7% and 46.5% had hyperlipidemia, 10.4% and 10.4% had metformin, and 25.8% and 25.4% had statin use, respectively. Males and females had similar mean Charlson Comorbidity Index scores (3.91 vs 1.96).

Investigators estimated, as well as compared by sex, the incidence of liver adverse events (cirrhosis, hepatic decompensation, and hepatocellular carcinoma) and non-liver adverse events (cardiovascular diseases, chronic kidney disease, and non-liver and non-sex-specific cancers). Investigators discovered, compared to men, that women had a greater incidence of any liver adverse event (12.72 vs 11.53) and cirrhosis (12.68 vs 11.55).

“[This is] consistent with the observation that MASLD is the primary indication for liver transplantation among women in the US,” investigators wrote.

As for men, they had a greater incidence of hepatic decompensation (10.40 vs 9.37), hepatocellular carcinoma (1.88 vs 0.73), CVD (17.89 vs 12.89), CKD (16.61 vs 14.42), and non-sex-specific cancer (6.68 vs 5.06). This finding expands the existing knowledge that men have greater CVD and cancer risks than women.

Women had a 9% greater risk of cirrhosis development compared with men. Moreover, compared to females, men had an 11% greater risk of hepatic decompensation and more than double the risk of hepatocellular carcinoma (hazard ratio [HR], 2.59; 95% CI, 2.39-2.80; P < .001). Men also had a 40% greater risk of CVD (HR, 1.40; 95% CI, 1.37 -1.43; P < .001), a 16% greater risk of chronic kidney disease (HR, 1.16; 95% CI, 1.13 -1.18; P < .001), and a 32% greater risk of non–sex-specific cancers (HR, 1.32; 95% CI, 1.27 -1.37; P < .001) than women.

At the 10-year follow-up, the restricted mean survival time analysis showed women had a significantly shorter mean time to the development of cirrhosis, and men had a significantly shorter mean time to hepatic decompensation, hepatocellular carcinoma, CVD, chronic kidney disease, and non-sex-specific cancers.

The team wrote how all participants had private health insurance in the US, and thus additional studies need to examine patients without insurance, only government-sponsored insurance, and those who live in other world regions.

“Our study provides robust evidence of significant sex differences in the risk of both liver and non-liver adverse events in patients with MASLD to support policies for sex-based preventive, monitoring, and therapeutic management strategies of MASLD,” investigators wrote.

References

1. ^{Yan T, Zhang X, Wong T, Cheung R, Nguyen MH. Sex Differences in Adverse Liver and Nonliver Outcomes in Steatotic Liver Disease. JAMA Netw Open. 2024;7(12):e2448946. doi:10.1001/jamanetworkopen.2024.48946}
2. ^{Le MH, Le DM, Baez TC, Wu Y, Ito T, Lee EY, Lee K, Stave CD, Henry L, Barnett SD, Cheung R, Nguyen MH. Global incidence of non-alcoholic fatty liver disease: A systematic review and meta-analysis of 63 studies and 1,201,807 persons. J Hepatol. 2023 Aug;79(2):287-295. doi: 10.1016/j.jhep.2023.03.040. Epub 2023 Apr 9. PMID: 37040843.}