Open AccessWhat proportion of people have a follow-up biopsy in randomized trials of treatments for non-alcoholic steatohepatitis?: A systematic review and meta-analysis
Author(s) -
Dimitrios A. Koutoukidis,
Elizabeth Morris,
John A. Henry,
Yusra Shammoon,
Matthew C. Zimmerman,
Moscho Michalopoulou,
Susan A. Jebb,
Paul Aveyard
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0250385
Subject(s) - medicine , steatohepatitis , randomized controlled trial , biopsy , meta analysis , liver biopsy , clinical trial , adverse effect , medline , fatty liver , disease , political science , law
Background and aim Trials of treatments for non-alcoholic steatohepatitis require endpoint assessment with liver biopsies. Previous large-scale trials have calculated their sample size expecting high retention but on average did not achieve this. We aimed to quantify the proportion of participants with a valid follow-up biopsy. Methods We conducted a systematic review of MEDLINE and Embase until May 2020 and included randomized clinical trials of any intervention in non-alcoholic steatohepatitis with at least 1-year follow-up. We were guided by Cochrane methods to run a meta-analysis with generalized linear mixed models with random effects. Results Forty-one trials (n = 6,695) were included. The proportion of participants with a valid follow-up biopsy was 82% (95%CI: 78%-86%, I 2 = 92%). There was no evidence of a difference by location, trial length, or by allocated treatment group. Reasons for missing follow-up biopsies were, in ranked order, related to participants (95 per 1,000 participants (95%CI: 69–129, I 2 = 92%), medical factors, protocol, trial conduct, and other/unclear. Biopsy-related serious adverse events occurred in 16 per 1,000 participants (95% CI: 8–33, I 2 = 54%). No biopsy-related deaths were reported. Conclusions The proportion of participants with a valid follow-up biopsy in therapeutic trials in non-alcoholic steatohepatitis is on average 82%, with around 1 in 10 participants declining a follow-up biopsy. These findings can inform adequately-powered trials.