Women have a lower risk of nonalcoholic fatty liver disease compared with men, but those who do develop the disease are significantly more likely than are men to develop advanced fibrosis, according to data from a meta-analysis of more than 62,000 individuals.
Sex disparity persists in most chronic liver diseases, with more cases and risk of progression reported in men, but the effect of sex on nonalcoholic fatty liver disease (NAFLD) remains unclear, wrote Maya Balakrishnan, MD, of Baylor College of Medicine, Houston, and colleagues. “Knowing whether and how [sex] influences the risk and severity of NAFLD is important for risk stratification, risk modification as well as prognostication,” they said.
In a study published in, the researchers conducted a review and meta-analysis of 54 studies, including data from 62,239 patients with NAFLD, 5,428 with nonalcoholic steatohepatitis (NASH), and 6,444 with advanced NAFLD fibrosis.
Overall, women had a 19% lower risk of developing NAFLD compared with men (pooled risk ratio 0.81), a similar risk to men of developing NASH (RR, 1.00), and a 37% increased risk of advanced fibrosis (RR, 1.37) compared with men.
The risk of more severe disease in women increased with age. Among women aged 50 years and older, the risks of NASH and advanced fibrosis were significantly higher, at 17% and 56%, respectively (RR, 1.17 and RR, 1.56). The sex-specific prevalence of advanced fibrosis was not significantly different in patients younger than 50 years.
“Our findings of an increased prevalence of severe phenotypes of NAFLD – NASH and advanced fibrosis – among older women fits well into the current understanding of disease pathogenesis,” the researchers noted.
The findings were limited by several factors, including the cross-sectional nature and heterogeneity of the included studies and lack of data on possible contributions to NASH and NAFLD such as polycystic ovarian syndrome, cumulative use of hormone therapy, and pregnancy, the researchers noted.
However, the results were strengthened by the large patient population. “Given the higher risk of advanced fibrosis observed among women compared to men with NAFLD in our meta-analysis, it is plausible that cirrhosis and its complications may occur with greater frequency among women than in men,” the researchers said. Consequently, women older than 50 years with NAFLD should be evaluated frequently for advanced disease, they noted. In addition, “more focused and intensified efforts may be warranted to target lifestyle modifications and weight loss among young women with NAFLD, particularly in the presence of NASH and/or advanced fibrosis,” the researchers concluded.
Conducting the study at this time was important because of conjectures of sex-based differences in NAFLD prevalence and NAFLD progression, Dr. Balakrishnan said in an interview. “However, the findings from studies conducted across different study populations have been disparate. Therefore, it was important to perform a systematic review and meta-analysis to determine whether there are differences in NAFLD and NAFLD severity risk between the [sexes],” she said.
Dr. Balakrishnan said she was surprised by the higher risk of severe NASH fibrosis in women compared with men once NAFLD is established. “This was surprising and sets NAFLD apart from other highly prevalent chronic liver disease etiologies,” she said. “Other common liver diseases, for example hepatitis B and hepatitis C, tend to be more common among men and tend to progress more rapidly, and tend to be more severe among men compared to women,” she noted.
The take-home message for clinicians is that NAFLD is at least equally, if not more, aggressive in women compared with men, and should be evaluated with equal aggressiveness, Dr. Balakrishnan emphasized. “Moreover, in the future we may expect to see the burden of cirrhosis distributed more equally among women and men than we have to date. This has implications for liver disease screening and women’s health,” she said. The next steps for research are to determine the specific reasons for the higher risk of NAFLD fibrosis in women compared with men, she added.
The study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.
SOURCE: Balakrishnan M et al. Clin Gastroenterol Hepatol. 2020 Apr 30.