CORRESPONDENCE The Influence of Menopause on the Development of Hepatic Fibrosis in Nonobese Women With Nonalcoholic Fatty Liver Disease To the Editor: We read the article by Yang et al. with great interest concerning the effect of postmenopausal status on the development of hepatic fibrosis.1 There is mounting evidence that menopause accelerates the progression and severity of nonalcoholic steatohepatitis. In their article, Yang et al. concluded that postmenopausal women are at higher risk of severe fibrosis, when compared to premenopausal women, and they concluded that this additional risk was attributable to the decrease in estrogen levels. In this study, the mean body mass index (BMI) was 44.6 and 39.2 for pre- and postmenopausal woman, respectively. These BMIs are also categorized as class III and II obesity, respectively, according to the World Health Organization. It is well known that estrogen is produced from fat cells in addition to the ovaries, which are the primary source of this hormone. This secondary source of estrogen is especially important in postmenopausal women. Indeed, postmenopausal obese women have higher estrogen levels than their nonobese postmenopausal counterparts.2 Because of these facts, reconfirmation of the results reported by Yang et al. in nonobese postmenopausal women may be needed. Therefore, we limited our target population to women with nonalcoholic fatty liver disease (NAFLD) whose BMI was less than 30 and compared the severity of hepatic fibrosis after menopause within this cohort. Utilizing the Japan Study Group of NAFLD (JSG-NAFLD) database,3 419 women with biopsy-proven NAFLD were included and comprised 90 premenopausal and 329 postmenopausal patients. As expected, even in nonobese NAFLD patients, postmenopausal women still had more severe fibrosis, when compared to the premenopausal subjects (P 5 0.0266; odds ratio [OR]: 2.173), after adjusting for hepatic inflammation, ballooning hepatocytes, BMI, impaired glucose tolerance/diabetes, and hypertension. Furthermore, this OR may be higher than that found in Yang et al.’s study. Our results reconfirm that postmenopausal women are more susceptible to development of hepatic fibrosis, and this may be caused by decreased levels of estrogen. With the increased incidence of obesity and diabetes globally, Yang et al.’s findings will become of increasing importance. However, the effects of estrogen on hepatic fibrosis may also need to be put in the context of the increasing age of the subjects, because this is a known factor in the development of liver disease. In conclusion, we hope the contents of this letter are useful for validation of the influence of menopause on the development of hepatic fibrosis.

Table 1. Multiple Logistic Regression Analysis of Factors Associated With Severe Fibrosis Factors

Postmenopausal woman Hepatocyte ballooning Necroinflammation BMI IGT/DM Hepertension

OR

95% CI

P Value

2.173 1.277 2.564 1.003 2.306 1.2193

1.124-4.473 0.882-1.857 1.808-3.696 0.914-1.103 1.365-4.000 0.757-1.976

0.0266 0.1963