TY - JOUR
TI - A randomised controlled trial of losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis
AU - McPherson, S.
AU - Wilkinson, N.
AU - Tiniakos, D.
AU - Wilkinson, J.
AU - Burt, A.D.
AU - McColl, E.
AU - Stocken, D.D.
AU - Steen, N.
AU - Barnes, J.
AU - Goudie, N.
AU - Stewart, S.
AU - Bury, Y.
AU - Mann, D.
AU - Anstee, Q.M.
AU - Day, C.P.
JO - PLOS ONE
PY - 2017
VL - 12
TODO - 4
SP - null
PB - Public Library of Science
SN - null
TODO - 10.1371/journal.pone.0175717
TODO - angiotensin receptor antagonist;  antifibrotic agent;  dipeptidyl carboxypeptidase inhibitor;  losartan;  placebo;  angiotensin 1 receptor antagonist;  losartan, adult;  aged;  antihypertensive therapy;  Article;  body mass;  clinical article;  clinical feature;  controlled study;  coronary artery disease;  diabetic patient;  disease course;  double blind procedure;  drug efficacy;  family planning;  female;  fibrosis;  follow up;  histopathology;  human;  human tissue;  liver biopsy;  liver cirrhosis;  male;  nonalcoholic fatty liver;  obesity;  quality of life;  randomized controlled trial;  clinical trial;  drug administration;  drug effects;  fibrosis;  liver;  liver cirrhosis;  middle aged;  multicenter study;  Non-alcoholic Fatty Liver Disease;  pathology;  treatment outcome;  young adult, Adult;  Aged;  Angiotensin II Type 1 Receptor Blockers;  Double-Blind Method;  Drug Administration Schedule;  Female;  Fibrosis;  Humans;  Liver;  Liver Cirrhosis;  Losartan;  Male;  Middle Aged;  Non-alcoholic Fatty Liver Disease;  Treatment Outcome;  Young Adult
TODO - Introduction: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease worldwide. Experimental and small clinical trials have demonstrated that angiotensin II blockers (ARB) may be anti-fibrotic in the liver. The aim of this randomised controlled trial was to assess whether treatment with Losartan for 96 weeks slowed, halted or reversed the progression of fibrosis in patients with non-alcoholic steatohepatitis (NASH). Methods: Double-blind randomised-controlled trial of Losartan 50 mg once a day versus placebo for 96 weeks in patients with histological evidence of NASH. The primary outcome for the study was change in histological fibrosis stage from pre-treatment to end-of-treatment. Results: The study planned to recruit 214 patients. However, recruitment was slower than expected, and after 45 patients were randomised (median age 55; 56% male; 60% diabetic; median fibrosis stage 2), enrolment was suspended. Thirty-two patients (15 losartan and 17 placebo) completed follow up period: one patient (6.7%) treated with losartan and 4 patients (23.5%) in the placebo group were "responders" (lower fibrosis stage at follow up compared with baseline). The major reason for slow recruitment was that 39% of potentially eligible patients were already taking an ARB or angiotensin converting enzyme inhibitor (ACEI), and 15% were taking other prohibited medications. Conclusions: Due to the widespread use of ACEI and ARB in patients with NASH this trial failed to recruit sufficient patients to determine whether losartan has anti-fibrotic effects in the liver. Trial registration: ISRCTN 57849521 © 2017 McPherson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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