Renin-angiotensin system inhibitors, type 2 diabetes and fibrosis progression in patients with NAFLD
Serena Pelusi1, Salvatore Petta2, Chiara Rosso3, Vittorio Borroni1, Anna Ludovica Fracanzani1, Paola Dongiovanni1, Antonio Craxi2, Elisabetta Bugianesi3, Silvia Fargion1, Luca Valenti1
1Internal Medicine, University of Milano, Fondazione IRCCS Ca Granda, Milano, Italy; 2University of Palermo, Palermo, Italy; 3University of Torino, Torino, Italy
Background&Aims: The clinical determinants of fibrosis progression in nonalcoholic fatty liver disease (NAFLD) are still under definition. Aim of this study was 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. 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.
Disclosures: The following people have nothing to disclose: Serena Pelusi, Salvatore Petta, Chiara Rosso, Vittorio Borroni, Anna Ludovica Fracanzani, Paola Dongiovanni, Antonio Craxi, Elisabetta Bugianesi, Silvia Fargion, Luca Valenti
