Serious Outcomes of Steatotic Liver Disease Hit Men and Women Differently

Serious outcomes associated with metabolic dysfunction-associated steatotic liver disease (MASLD) — including liver cancer, cirrhosis, heart disease, and more — affect men and women differently, a large cohort study of privately insured Americans indicated.

Men had a more than twofold greater risk of hepatocellular carcinoma (HCC) compared with women (HR 2.59, 95% CI 2.39-2.80) along with an 11% higher risk of hepatic decompensation (HR 1.11, 95% CI 1.08-1.14) over 10 years of follow-up, according to a propensity score-matched analysis.

Women, meanwhile, had a 9% greater risk both of any adverse liver event or of cirrhosis specifically compared with men (P<0.001 for all), reported Mindie Nguyen, MD, MAS, of Stanford University Medical Center in Palo Alto, California, and colleagues.

“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,” the team noted in JAMA Network Open. “We found higher incidence and risk of cirrhosis in women, consistent with the observation that MASLD is the primary indication for liver transplantation among women in the U.S. As in prior studies reporting higher HCC risk in men with other chronic liver diseases vs women, our study found a significant association between male sex and increased HCC risk among patients with MASLD.”

In terms of non-liver adverse outcomes, men in the study also had greater risks for cardiovascular disease (HR 1.40, 95% CI 1.37-1.43), chronic kidney disease (HR 1.16, 95% CI 1.13-1.18), and non-sex-specific cancers (HR 1.32, 95% CI 1.27-1.37).

“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,” the researchers concluded.

Roughly 30% of people worldwide are affected by MASLD, a number that continues to climb. While there are no treatments approved for the condition, lifestyle changes such as weight loss and exercise can reduce the associated risks. MASLD was previously called nonalcoholic fatty liver disease.

For their study, Nguyen’s group pulled data on 761,403 U.S. adults with MASLD in the Merative MarketScan Research Database from 2007 to 2022. From there, they used propensity-score matching to assemble 344,436 pairs of men and women with similar characteristics for comparison.

Included subjects were 53 years of age on average and had a mean Charlson Comorbidity Index of 3.91. About a third had diabetes, 17% had obesity, over 60% had hypertension, and a little less than half had hyperlipidemia. In terms of medications, 10% had a history of metformin use and one-fourth used statins.

The 10-year cumulative incidence of liver and non-liver events with significant differences between men and women were as follows:

• Cirrhosis: 9.9% vs 11%, respectively
• Hepatic decompensation: 8.3% vs 8%
• HCC: 1.7% vs 0.7%
• Cardiovascular disease: 20.4% vs 14.9%
• Chronic kidney disease: 16.9% vs 14.9%
• Non-sex-specific cancers: 7.7% vs 6%

No significant differences were observed when it came to overall non-liver cancers.

A restricted mean survival time analysis “showed that women had significantly shorter mean time to the development of cirrhosis,” according to the study authors, while men had a shorter time to hepatic decompensation, HCC and other non-sex-specific cancers, and heart or chronic kidney disease.

Study limitations included that only individuals with private insurance were involved.

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