A randomised controlled trial of losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis.
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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5395178?pdf=render |
| _version_ | 1811211117241827328 |
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| author | Stuart McPherson Nina Wilkinson Dina Tiniakos Jennifer Wilkinson Alastair D Burt Elaine McColl Deborah D Stocken Nick Steen Jane Barnes Nicola Goudie Stephen Stewart Yvonne Bury Derek Mann Quentin M Anstee Christopher P Day |
| author_facet | Stuart McPherson Nina Wilkinson Dina Tiniakos Jennifer Wilkinson Alastair D Burt Elaine McColl Deborah D Stocken Nick Steen Jane Barnes Nicola Goudie Stephen Stewart Yvonne Bury Derek Mann Quentin M Anstee Christopher P Day |
| author_sort | Stuart McPherson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T05:07:15Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T05:07:15Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b338d05dc43343f1b0265870bb848d7b2022-12-22T03:46:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01124e017571710.1371/journal.pone.0175717A randomised controlled trial of losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis.Stuart McPhersonNina WilkinsonDina TiniakosJennifer WilkinsonAlastair D BurtElaine McCollDeborah D StockenNick SteenJane BarnesNicola GoudieStephen StewartYvonne BuryDerek MannQuentin M AnsteeChristopher P DayINTRODUCTION: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.http://europepmc.org/articles/PMC5395178?pdf=render |
| spellingShingle | Stuart McPherson Nina Wilkinson Dina Tiniakos Jennifer Wilkinson Alastair D Burt Elaine McColl Deborah D Stocken Nick Steen Jane Barnes Nicola Goudie Stephen Stewart Yvonne Bury Derek Mann Quentin M Anstee Christopher P Day A randomised controlled trial of losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis. PLoS ONE |
| title | A randomised controlled trial of losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis. |
| title_full | A randomised controlled trial of losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis. |
| title_fullStr | A randomised controlled trial of losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis. |
| title_full_unstemmed | A randomised controlled trial of losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis. |
| title_short | A randomised controlled trial of losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis. |
| title_sort | randomised controlled trial of losartan as an anti fibrotic agent in non alcoholic steatohepatitis |
| url | http://europepmc.org/articles/PMC5395178?pdf=render |
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