Sarcopenia is an independent risk factor for non-alcoholic steatohepatitis and significant fibrosis

Abstract

Background & aims: We explored whether sarcopenia is associated with the histological severity of non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis (NASH) and significant fibrosis.

Methods: In a biopsy-proven NAFLD cohort, the appendicular skeletal muscle mass (ASM) was measured. Sarcopenia was defined as a ASM/body weight (ASM%) value beyond two standard deviations below the mean for healthy young adults.

Results: Among the entire set of 309 subjects, the prevalence of sarcopenia in subjects without NAFLD, with non-alcoholic fatty liver (NAFL), and with NASH were 8.7%, 17.9%, and 35.0%, respectively (p<0.001). ASM% was inversely correlated with the severity of fibrosis (p<0.001), and the prevalence of significant fibrosis (⩾F2) was higher in subjects with sarcopenia than in those without (45.7% vs. 24.7%; p<0.001). A crude analysis revealed that sarcopenia was associated with NAFLD (odds ratio [OR], 3.82; 95% confidence interval [CI], 1.58-9.25), which became insignificant after adjustment for body mass index (BMI), diabetes, and hypertension. Among NAFLD subjects, subjects with sarcopenia were more likely to have NASH than those without sarcopenia through a multivariate analysis adjusted for age, gender, BMI, hypertension, diabetes, and smoking status (OR, 2.28; 95% CI, 1.21-4.30), and this finding was obtained even after adjustment for insulin resistance (OR, 2.30; 95% CI, 1.08-4.93). Sarcopenia was also associated with significant fibrosis independent of BMI and insulin resistance (OR, 2.05; 95% CI, 1.01-4.16).

Conclusions: In this large biopsy-proven NAFLD cohort, sarcopenia was significantly associated with NASH and significant fibrosis.

Lay summary: Low muscle mass was found to be associated with histological severity in non-alcoholic fatty liver disease, and sarcopenia was significantly associated with non-alcoholic steatohepatitis and significant fibrosis, independent of obesity, inflammation, and insulin resistance. Clinical trial number: NCT 02206841.

Keywords: Appendicular skeletal muscle mass; Body weight; Diabetes; Fibrosis; Hepatic steatosis; Insulin resistance; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Sarcopenia.