Patient Sex, Reproductive Status, and Synthetic Hormone Use Associate With Histologic Severity of Nonalcoholic Steatohepatitis

Abstract

Sex and sex hormones can affect responses of patients with nonalcoholic fatty liver disease (NAFLD) to metabolic stress and development of hepatocyte injury and inflammation. We collected data from 3 large US studies of patients with NAFLD (between October 2004 and June 2013) to assess the association between histologic severity and sex, menopause status, synthetic hormone use, and menstrual abnormalities in 1112 patients with a histologic diagnosis of NAFLD. We performed logistic or ordinal logistic regression models, adjusting for covariates relevant to an increase of hepatic metabolic stress. We found that pre-menopausal women were at an increased risk of lobular inflammation, hepatocyte ballooning, and Mallory-Denk bodies than men and also at an increased risk of lobular inflammation and Mallory-Denk bodies than post-menopausal women (P<.01). Use of oral contraceptives was associated with an increased risk of lobular inflammation and Mallory-Denk bodies in pre-menopausal women, whereas hormone replacement therapy was associated with an increased risk of lobular inflammation in post-menopausal women (P<.05). We conclude that being a pre-menopausal woman or a female user of synthetic hormones is associated with increased histologic severity of hepatocyte injury and inflammation among patients with NAFLD at given levels of hepatic metabolic stress.

Sex Differences in Nonalcoholic Fatty Liver Disease: State of the Art and Identification of Research Gaps

“…In an NAFLD registry study, Mallory‐Denk bodies appeared only after puberty, while severe portal inflammation was more prevalent before puberty . In another NAFLD registry study of adults, premenopausal women had more severe lobular inflammation, hepatocyte ballooning, and Mallory‐Denk bodies than men or postmenopausal women after adjusting for variables defining hepatic metabolic stress . This suggests that sex hormones modulate hepatic injury/inflammation for any given level of metabolic stress.…”

“…Although premenopausal women have more severe hepatocyte injury and inflammation, they have less hepatic fibrosis compared to men and postmenopausal women, suggesting multiphasic effects of sex and hormones on NAFLD pathogenesis (Fig. ).…”

Voluntary Wheel Running Reduces the Acute Inflammatory Response to Liver Carcinogen in a Sex-specific Manner

“…Furthermore, premenopausal women with NASH (nonalcoholic steatohepatitis) show decreased risk of developing liver fibrosis compared with men and postmenopausal women (32). Despite this, premenopausal women had an increased risk of developing the hepatic inflammation itself, with lobular inflammation and hepatocyte ballooning, and this risk is further increased by use of oral contraceptives (33).…”

Schützen Östrogene Frauen vor der Fettleber?

“…Ob eine Hormonersatztherapie das Risiko für NASH und/oder Fibrose senkt, ist bislang nicht klar [2]. Eine weitere klinische Studie berichtet jedoch auch, dass synthetische Hormone mit lobulärer Inflammation der Leber vergesellschaftet waren, dies wurde jedoch auf die Gestagenkomponente zurückgeführt [20].…”