title: Renin-Angiotensin System Inhibitors, Type 2 Diabetes and Fibrosis Progression: An Observational Study in Patients with Nonalcoholic Fatty Liver Disease.
abstract: BACKGROUND
  The clinical determinants of fibrosis progression in nonalcoholic fatty liver disease (NAFLD) are still under definition.
  
  
  OBJECTIVE
  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.
authors.affiliation: Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Pelusi
authors.affiliation: Gastroenterology, Università di Palermo, Palermo, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Petta
authors.affiliation: Gastroenterology, Dept. of Medical Sciences, Università di Torino, Torino, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Rosso
authors.affiliation: Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Borroni
authors.affiliation: Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.
authors.forename: Anna Ludovica
authors.initials: AL
authors.lastname: Fracanzani
authors.affiliation: Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Dongiovanni
authors.affiliation: Gastroenterology, Università di Palermo, Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxi
authors.affiliation: Gastroenterology, Dept. of Medical Sciences, Università di Torino, Torino, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bugianesi
authors.affiliation: Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fargion
authors.affiliation: Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.
authors.forename: Luca
authors.identifier: http://orcid.org/0000-0001-8909-0345
authors.initials: L
authors.lastname: Valenti
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018450:Disease Progression; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007558:Italy; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy*; D011379:Prognosis; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012189:Retrospective Studies; D062606:Tertiary Care Centers
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008687:Metformin