What influences treatment response in animal models of non-alcoholic fatty liver disease? A meta-analysis with meta-regression.

Abstract

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.