RT Journal Article
T1 Systematic review and meta-analysis: analysis of variables influencing the interpretation of clinical trial results in NAFLD.
A1 Ampuero, Javier
A1 Gallego-Durán, Rocío
A1 Maya-Miles, Douglas
A1 Montero, Rocío
A1 Gato, Sheila
A1 Rojas, Ángela
A1 Gil, Antonio
A1 Muñoz, Rocío
A1 Romero-Gómez, Manuel
K1 Drug
K1 Fibrosis
K1 NAFLD
K1 NASH
K1 Placebo
AB NAFLD clinical trials have shown suboptimal results, particularly for liver fibrosis, despite the robust preclinical drug development. We aimed to assess the histological response after the experimental treatment versus placebo by carrying out a meta-analysis of NAFLD clinical trials. After a systematic review of NAFLD clinical trials to May 2021, applying strict selection criteria, the following primary outcomes were observed: (a) NASH resolution, with no worsening of fibrosis when available; (b) fibrosis improvement  ≥ 1 stage, with no worsening of NAS when available; (c) worsening of NAS; (d) worsening of liver fibrosis  ≥ 1 stage, including the progression to cirrhosis on histopathology. Other histological, clinical, and biochemical outcomes were considered secondary endpoints. Heterogeneity was explored by subgroup and sensitivity analyses, and univariable meta-regression. Twenty-seven randomized clinical trials were included. The pooled efficacy for NASH resolution receiving experimental therapy was 19% (95%CI 15-23; I2 96.2%) compared with placebo 10% (95%CI 7-12; I2 85.8%) (OR 1.66 (95%CI 1.24-2.21); I2 57.8%), while it was 26% (95%CI 22-29); I2 90%)) versus 18% (95%CI 15-21; I2 59%)) for fibrosis improvement (OR 1.34 (95%CI 1.13-1.58); I2 25.4%). For these outcomes, the therapy showed higher efficacy in trials longer than 48 weeks, with   This meta-analysis provides information about the efficacy of the therapy versus placebo by comparing different and combined trial outcomes such as NASH resolution, fibrosis improvement, and NAS and fibrosis worsening. Changes in the experimental design and selection criteria of the clinical trials might be suitable to increase the efficacy.
YR 2022
FD 2022-03-24
LK http://hdl.handle.net/10668/20330
UL http://hdl.handle.net/10668/20330
LA en
DS RISalud
RD Apr 7, 2025