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Meta-Analysis
. 2023 Jan;29(1):33-39.
doi: 10.1016/j.eprac.2022.10.007. Epub 2022 Oct 20.

A Meta-analysis on Associated Risk of Mortality in Nonalcoholic Fatty Liver Disease

Clarissa Elysia Fu  1 , Cheng Han Ng  2 , Jie Ning Yong  1 , Kai En Chan  1 , Jieling Xiao  1 , Benjamin Nah  3 , Shirley Huey Shin Bong  4 , Khin Maung Win  5 , Aung Hlaing Bwa  5 , Wen Hui Lim  1 , Darren Jun Hao Tan  1 , Rebecca Wenling Zeng  1 , Nicholas Chew  6 , Margaret L P Teng  3 , Mohammad Shadab Siddiqui  7 , Jude A Oben  8 , Arun J Sanyal  7 , Vincent Wai-Sun Wong  9 , Mazen Noureddin  10 , Mark Muthiah  11
Affiliations
Meta-Analysis

A Meta-analysis on Associated Risk of Mortality in Nonalcoholic Fatty Liver Disease

Clarissa Elysia Fu et al. Endocr Pract. 2023 Jan.

Abstract

Objective: Nonalcoholic fatty liver disease (NAFLD) affects much of the worldwide population and poses a significant burden to the global healthcare. The rising numbers of individuals with NAFLD and instances of mortality point toward the importance of understanding the association causes of mortality in NAFLD. This meta-analysis aimed to seek the associations of NAFLD with all-cause, cardiovascular disease (CVD)-related, liver-related, and cancer-related mortality.

Methods: MEDLINE and Embase were searched for articles relating to causes of mortality between NAFLD and non-NAFLD. The DerSimonian and Laird random-effects model was used to analyze adjusted hazard ratios (HR), and a sensitivity analysis was conducted to reduce heterogeneity through a graphical display of study heterogeneity.

Results: Fifteen studies involving 10 286 490 patients were included. Individuals with NAFLD exhibited an increased risk of all-cause mortality (HR, 1.32; 95% CI, 1.09-1.59; P < .01; I2 = 96.00%), CVD-related mortality (HR, 1.22; 95% CI, 1.06-1.41; P < .01; I2 = 81.00%), and cancer-related mortality (HR, 1.67; 95% CI, 1.15-2.41; P < .01; I2 = 95.00%). However, no significant association was found between liver-related mortality and NAFLD (HR, 3.58; 95% CI, 0.69-18.46; P =.13; I2 = 96.00%). The sensitivity analysis conducted with graphic display of heterogeneity and only population-based studies found similar results.

Conclusion: NAFLD was associated with an increased risk of all-cause, CVD-related, and cancer-related mortality but not liver-related mortality. The finding is likely because of low fibrosis prevalence in the community. However, the significant burden in other causes of mortality beyond the liver points to a need for multidisciplinary efforts to reduce the mortality risks.

Keywords: CVD; NAFLD; meta-analysis; mortality.

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Conflict of interest statement

Disclosure A.J.S. is the President of Sanyal Biotechnology and has stock options in Genfit, Akarna, Tiziana, Indalo, Durect, and Galmed. He has served as a consultant to Astra Zeneca, Nitto Denko, Enyo, Ardelyx, Conatus, Nimbus, Amarin, Salix, Tobira, Takeda, Jannsen, Gilead, Terns, Birdrock, Merck, Valeant, Boehringer Ingelheim, Lilly, Hemoshear, Zafgen, Novartis, Novo Nordisk, Pfizer, Exhalenz, and Genfit. He has been an unpaid consultant to Intercept, Echosens, Immuron, Galectin, Fractyl, Syntlogic, Affimune, Chemomab, Zydus, Nordic Bioscience, Albireo, Prosciento, Surrozen, and Bristol Myers Squibb. His institution has received grant support from Gilead, Salix, Tobira, Bristol Myers, Shire, Intercept, Merck, AstraZeneca, Malinckrodt, Cumberland, and Norvatis. He receives royalties from Elsevier and UptoDate. M.N. has been on the advisory board/consultant for 89BIO, Altimmune, Gilead, cohBar, Cytodyn, Intercept, Pfizer, Novo Nordisk, Blade, EchoSens, Fractyl, Madrgial, NorthSea, Prespecturm, Terns, Siemens, and Roche Diagnostic. He has received research support from Allergan, BMS, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Madrigal, Novartis, Pfizer, Shire, Viking, and Zydus. He is a shareholder or has stocks in Anaetos, Chrownwell, Ciema, Rivus Pharma, and Viking. V.W.-S.W. has served as an advisory board member or consultant for 3V-BIO, AbbVie, Allergan, Boehringer Ingelheim, Echosens, Gilead Sciences, Inventiva, Merck, Novartis, Novo Nordisk, Pfizer, ProSciento, Sagimet Biosciences, TARGET PharmaSolutions, and Terns. He is on the speaker's bureau for Abbott, AbbVie, Echosens, Gilead Sciences, and Novo Nordisk. He has received a grant from Gilead Sciences for fatty liver research and is a cofounder of Illuminatio Medical Technology Limited. All authors have made substantial contributions to all of the following: (1) the conception and design of the study, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, and (3) final approval of the version to be submitted. No writing assistance was obtained in the preparation of the manuscript. The manuscript, including related data, figures, and tables, has not been previously published, and the manuscript is not under consideration elsewhere.

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