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A randomised controlled trial of losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis

Lookup NU author(s): Dr Stuart McPherson, Dr Nina Wilson, Dr Dina Tiniakos Tiniakos, Dr Jennifer Wilkinson, Professor Alastair Burt, Professor Elaine McColl, Dr Deborah Stocken, Dr Ian Steen, Jane Barnes, Nicola Goudie, Dr Yvonne Bury, Professor Derek Mann, Professor Quentin Anstee, Professor Chris Day

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 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. 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


Publication metadata

Author(s): McPherson S, Wilkinson N, Tiniakos D, Wilkinson J, Burt AD, McColl E, Stocken DD, Steen N, Barnes J, Goudie N, Stewart S, Bury Y, Mann D, Anstee QM, Day CP

Publication type: Article

Publication status: Published

Journal: PLoS One

Year: 2017

Volume: 12

Issue: 4

Online publication date: 18/04/2017

Acceptance date: 29/03/2017

ISSN (electronic): 1932-6203

Publisher: Public Library of Science

URL: https://doi.org/10.1371/journal.pone.0175717

DOI: 10.1371/journal.pone.0175717


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