Renin-Angiotensin System Inhibitors, Type 2 Diabetes and Fibrosis Progression: An Observational Study in Patients with Nonalcoholic Fatty Liver Disease
BACKGROUND
The clinical determinants of fibrosis progression in nonalcoholic fatty liver disease (NAFLD) are still under definition.


AIM
To assess the clinical determinants of fibrosis progression rate (FPR) in NAFLD patients with baseline and follow-up histological evaluation, with a special focus on the impact of pharmacological therapy.


METHODS
In an observational cohort of 118 Italian patients from tertiary referral centers, liver histology was evaluated according to Kleiner. Independent predictors of FPR were selected by a stepwise regression approach.


RESULTS
Median follow-up was 36 months (IQR 24-77). Twenty-five patients (18%) showed some amelioration, 63 (53%) had stability, 30 (25%) had progression of fibrosis. Patients with nonalcoholic steatohepatitis (NASH) had similar demographic and anthropometric features, but a higher prevalence of type 2 diabetes (T2D; p = 0.010), and use of renin-angiotensin axis system (RAS) inhibitors (p = 0.005). Fibrosis progression was dependent of the length of follow-up, and was associated with, but did not require, the presence of NASH (p<0.05). Both fibrosis progression and faster FPR were independently associated with higher APRI score at follow-up, absence of treatment with RAS inhibitors, and T2D diagnosis at baseline (p<0.05). There was a significant interaction between use of RAS inhibitors and T2D on FPR (p = 0.002). RAS inhibitors were associated with slower FPR in patients with (p = 0.011), but not in those without (p = NS) T2D.


CONCLUSIONS
NASH is not required for fibrosis progression in NAFLD, whereas T2D seems to drive fibrogenesis independently of hepatic inflammation. Use of RAS inhibitors may contrast fibrosis progression especially in high-risk patients affected by T2D.