Among patients with nonalcoholic fatty liver disease, postmenopausal women have the highest risk for advanced fibrosis, new research shows.
“Postmenopausal women with NAFLD are a high-risk group of patients,” study author Maya Balakrishnan, MD, an assistant professor of gastroenterology at Baylor College of Medicine, in Houston, told Gastroenterology & Endoscopy News. “This is a paradigm shift in how we think of liver disease, which has traditionally been thought of as something that affects men more than women.”
Because advanced fibrosis is the strongest predictor of progression to cirrhosis, decompensated liver disease and liver-related mortality, it is critical that providers identify NAFLD patients with advanced fibrosis for timely treatment to resolve NASH and reverse fibrosis, she said.
In an earlier meta-analysis, Dr. Balakrishnan and her colleagues showed that, in the general population, women had a lower risk for NAFLD than men (Clin Gastroenterol Hepatol 2021;19[1]:61-71.e15). But among those diagnosed with NAFLD, women around age 50 years had a higher risk for advanced fibrosis than men of the same age. Animal models of hepatic steatosis show that loss of estrogen may hasten progression of liver fibrosis, and some clinical studies have linked menopause with increased visceral fat, type 2 diabetes and NAFLD.
Taken together, these data suggest that menopause may be driving the increased risk for advanced fibrosis in women with NAFLD, Dr. Balakrishnan said.
To test this hypothesis, she and her colleagues conducted a cross-sectional study of 108 postmenopausal women, 107 premenopausal women and 55 men, all of whom had biopsy-proven NAFLD. The group’s average age was 47.4 years, and 27% had advanced fibrosis.
Most of the people in this cohort—the Harris County NAFLD Cohort in Houston, which began prospective recruitment in 2015—were of Mexican or Central American descent.
The investigators compared the presence of advanced fibrosis among premenopausal women, postmenopausal women and men, and determined menopausal status using a baseline questionnaire when available (they assumed menopausal status for women ages 50 or older who did not complete a questionnaire).
After adjusting for type 2 diabetes and hypertension, the risk for advanced fibrosis was 2.3 times higher in postmenopausal versus premenopausal women (odds ratio [OR], 2.34; 95% CI, 1.20-4.57). The risk for advanced fibrosis was also 2.5 times higher in women older than 50 than in younger women (95% CI, 1.23-5.13). Older and younger men showed similar risk levels, as did men compared with premenopausal women.
The findings have important implications for how physicians counsel women with NAFLD, Dr. Balakrishnan said. “In my practice, I discuss with women the possibility of more rapid disease progression as they approach age 50.”
Clinicians should be vigilant in their systematic stratification of fibrosis risk in these patients, and in educating patients about the importance of lifestyle modifications, she said.
“Lifestyle modification and weight loss are the main interventions for NAFLD and should be aggressively pursued among postmenopausal women, though they may need to be specifically adapted for the needs of postmenopausal women with NAFLD,” Dr. Balakrishnan said. “As medications become approved for NASH [non-alcoholic steatohepatitis], their effect among postmenopausal women, in particular, will need to be addressed.”
“This study helps clarify why women have a higher risk for NAFLD-associated fibrosis compared to men, and suggests that adding menopausal state to our risk stratification will better improve screening strategies to identify those with the highest risk for liver events,” said Nancy Reau, MD, the section chief of hepatology at Rush Medical College, in Chicago.
Still, she said the relationship between sex hormones and NAFLD risk is far from clear. Women with polycystic ovarian syndrome also have a higher risk for NASH, Dr. Reau said, which suggests that testosterone—not just loss of estrogen—may play a role in hepatic risk for women.
—Adam Leitenberger
Drs. Balakrishnan and Reau reported no relevant financial disclosures.
This article is from the August 2021 print issue.