@article{32cefb5b66ed49828694c7043ad7eb98,
title = "Placebo effect on progression and regression in NASH: Evidence from a meta-analysis",
abstract = "Background and Aims: The evaluation of the natural history of NASH has been limited. Currently, liver biopsy remains the gold standard in the assessment of NASH. Placebo-controlled trials represent a controlled environment with paired biopsies for the evaluation of NASH. This meta-analysis thus seeks to quantify the change severity of NASH over time, with patients on placebo arms from randomized controlled trials (RCTs) to examine the natural history of NASH. Methods: A search was conducted to include NASH RCTs with placebo treatment arms. Primary outcomes were (1) the resolution of NASH without worsening of fibrosis, (2) two-point reduction in NAFLD activity score without worsening of fibrosis, and (3) at least one-point reduction in fibrosis. Generalized linear mix model was used to estimate pooled proportion and mean differences. Results: This meta-analysis of 43 RCTs included 2649 placebo-treated patients. The pooled estimate of NASH resolution and two-point NAFLD activity score reduction without worsening of fibrosis was 11.65% (95% CI: 7.98-16.71) and 21.11% (95% CI: 17.24-25.57). The rate of ≥1 stage reduction and progression of fibrosis was 18.82% (95% CI: 15.65-22.47) and 22.74% (CI: 19.63-26.17), respectively. Older age and African American ethnicity was associated with lower NASH resolution rate in placebo-treated patients. Conclusions: Despite the absence of any pharmacological interventions, a significant proportion of patients in the placebo arm demonstrated improvements in liver histology, highlighting the possibility that NASH is a disease that can not only progress but regress spontaneously over time. Additionally, histologic response in placebo-treated patients is helpful in future design of phase 2B and phase 3 trials.",
author = "Ng, {Cheng Han} and Jieling Xiao and Lim, {Wen Hui} and Chin, {Yip Han} and Yong, {Jie Ning} and Tan, {Darren Jun Hao} and Phoebe Tay and Nicholas Syn and Roger Foo and Mark Chan and Nicholas Chew and Tan, {Eunice X.X.} and Huang, {Daniel Q.} and Dan, {Yock Young} and Nobuharu Tamaki and Siddiqui, {Mohammad Shadab} and Sanyal, {Arun J.} and Rohit Loomba and Mazen Noureddin and Muthiah, {Mark D.}",
note = "Funding Information: Dr. Huang consults for Eisai. Dr. Noureddin advises and received grants from Gilead. He received grants and owns stock in Viking. He advises 89Bio, Intercept, Pfizer, Novo Nordisk, Blade, Echosens, Fractyl, Terns, Siemens, and Roche. He received grants from Allergan, Bristol‐Myers Squibb, Galmed, Galectin, Genfit, Conatus, Enanta, Madrigal, Novartis, Shire, and Zydus. He owns stock in Anaetos and Rivus. Dr. Sanyal consults and received grants from Conatus, Gilead, Mallinckrodt, Immuron, Boehringer Ingelheim, Novartis, Bristol‐Myers Squibb, Merck, Eli Lilly, Novo Nordisk, Fractyl, Siemens, Madrigal, Inventiva, and Covance. He consults and owns stock in Genfit. He consults for Intercept, Pfizer, Salix, Galectin, Hemoshear, Terns, Albireo, Sanofi, Janssen, Takeda, Northsea, AMRA, Perspectum, Poxel, 89 Bio, AstraZeneca, NGM, Amgen, Regeneron, Genentech, Roche, Prosciento, Histoindex, Path AI, and Biocellvia. He received grants from Echosens‐Sandhill, Owl, and Second Genome. He owns stock in Exhalenz, Sanyal Bio, Durect, Indalo, Tiziana, and Rivus. He received royalties from Elsevier and UptoDate. Dr. Loomba consults and received grants from AstraZeneca, Bristol‐Myers Squibb, Eli Lilly, Galmed, Gilead, Intercept, Inventiva, Janssen, Madrigal, Merck, NGM, and Pfizer. He consults for Aardvark, Altimmune, Alnylam/Regeneron, Amgen, Arrowhead, CohBar, Glympse, High Tide, Inipharm, Ionis, Metacrine, Novartis, Novo Nordisk, Sagimet, Theratechnologies, 89 Bio, and Viking. He received grants from Allergan, Boehringer Ingelheim, Galectin, Genfit, and Sonic Incytes. Publisher Copyright: {\textcopyright} 2022 American Association for the Study of Liver Diseases.",
year = "2022",
month = jun,
doi = "10.1002/hep.32315",
language = "English (US)",
volume = "75",
pages = "1647--1661",
journal = "Hepatology",
issn = "0270-9139",
publisher = "Wiley",
number = "6",
}