RT Journal Article
SR Electronic
T1 What influences treatment response in animal models of non-alcoholic fatty liver disease? A meta-analysis with meta-regression
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2019.12.31.887919
DO 10.1101/2019.12.31.887919
A1 Hunter, Harriet
A1 de Gracia Hahn, Dana
A1 Duret, Amedine
A1 Im, Yu Ri
A1 Cheah, Qinrong
A1 Dong, Jiawen
A1 Fairey, Madison
A1 Hjalmarsson, Clarissa
A1 Li, Alice
A1 Lim, Hong Kai
A1 McKeown, Lorcán
A1 Mitrofan, Claudia-Gabriela
A1 Rao, Raunak
A1 Utukuri, Mrudula
A1 Rowe, Ian A.
A1 Mann, Jake P.
YR 2020
UL http://biorxiv.org/content/early/2020/02/25/2019.12.31.887919.abstract
AB The classical drug development pipeline necessitates studies using animal models of human disease to gauge future efficacy in humans, however, there is a comparatively low conversion rate from success in animals to in humans. Non-alcoholic fatty liver disease (NAFLD) is a complex chronic disease without any licensed therapies and hence a major field of animal research. We performed a meta-analysis of 414 interventional rodent studies (6,575 animals) in NAFLD to assess the mean difference in hepatic triglyceride content. 20 of 21 studied drug classes had similar efficacy with a mean difference of −30% hepatic triglyceride. However, when publication bias was accounted for, this reduced to −16% difference. Study characteristics were only able to account for a minority of variability on meta-regression, and we replicated previous findings of high risk of bias across 82% of cohorts. These findings build on previous work in preclinical neuroscience and help to explain the challenge of reproducibility and translation within the field of metabolism.