Clinical implications of renin-angiotensin system inhibitors for development and progression of non-alcoholic fatty liver disease

Abstract

Recently, there has been an increasing interest in the therapeutic efficacy of RAS inhibitors (RASi) in patients with non-alcoholic fatty liver disease (NAFLD) because they may reduce oxidative stress, inflammatory markers, and enhanced fibrosis. An objective of this study was to investigate the role of RASi on NAFLD development and progression in a large cohort. We conducted a nested case-control study. Study subjects were classified into two study cohorts according to baseline NAFLD status: non-NAFLD (n = 184,581) and established NALFD (n = 27,565). An NAFLD development or progression case was defined as a patient with newly developed NAFLD or new progression of advanced fibrosis from non-NAFLD and established NALFD cohorts, respectively. A conditional logistic regression analysis was conducted to estimate the associations between RASi exposure and NAFLD development/progression. Overall, no significant association was evident between RASi use and NAFLD development or progression (NAFLD development; ever-user vs. never-user: OR 1.017; 95% CI 0.842-1.230, NAFLD progression; ever-user vs. never-user: aOR 0.942; 95% CI 0.803-1.105). RASi ever-use in cases of individuals who were obese or who had normal fasting plasma glucose (FPG) was associated with reduced risk of both NAFLD development (body mass index (BMI) ≥ 25 kg/m²: 0.708 [95% confidence interval (CI) 0.535-0.937], FPG of < 100 mg/mL: 0.774 [95% CI 0.606-0.987]) and progression (BMI ≥ 25 kg/m²: 0.668 [95% CI 0.568-0.784], FPG of < 100 mg/mL: 0.732 [95% CI 0.582-0.921]). The present study did not verify a significant overall association between RASi use and NAFLD development/progression but suggested that RASi might prevent NAFLD development and progression among specific subjects.

Figure 1

Diagrams depicting the nested case–control study design. (A) Flow chart of inclusion and exclusion criteria of the study population. (B) Timeline of the study.