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Meta-Analysis
. 2022 Jul;28(3):483-496.
doi: 10.3350/cmh.2021.0406. Epub 2022 Mar 2.

Non-alcoholic fatty liver disease increases risk of carotid atherosclerosis and ischemic stroke: An updated meta-analysis with 135,602 individuals

Ansel Shao Pin Tang  1 , Kai En Chan  1 , Jingxuan Quek  1 , Jieling Xiao  1 , Phoebe Tay  1 , Margaret Teng  2 , Keng Siang Lee  3 , Snow Yunni Lin  1 , May Zin Myint  4 , Benjamin Tan  4 , Vijay K Sharma  4 , Darren Jun Hao Tan  1 , Wen Hui Lim  1 , Apichat Kaewdech  5 , Daniel Huang  1   2   6 , Nicholas Ws Chew  1   7 , Mohammad Shadab Siddiqui  8 , Arun J Sanyal  8 , Mark Muthiah  2   6 , Cheng Han Ng  1
Affiliations
Meta-Analysis

Non-alcoholic fatty liver disease increases risk of carotid atherosclerosis and ischemic stroke: An updated meta-analysis with 135,602 individuals

Ansel Shao Pin Tang et al. Clin Mol Hepatol. 2022 Jul.

Abstract

Background/aims: Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD.

Methods: Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD.

Results: From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval [CI], 27.36-43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37-4.32; P<0.0001). Pooled analysis of 25,839 patients with NAFLD found the prevalence of stroke to be 5.04% (95% CI, 2.74-9.09%) with an odds ratio of 1.88 (95% CI, 1.23-2.88; P=0.02) compared to non-NAFLD. The degree of steatosis assessed by ultrasonography in NAFLD was closely associated with risk of carotid atherosclerosis and stroke. Older age significantly increased the risk of developing carotid atherosclerosis, but not stroke in NAFLD.

Conclusion: This meta-analysis shows that a stepwise increment of steatosis of NAFLD can significantly increase the risk of carotid atherosclerosis and stroke development in NAFLD. Patients more than a third sufferred from carotid atherosclerosis and routine assessment of carotid atherosclerosis is quintessential in NAFLD.

Keywords: Atherosclerosis; Ischemic stroke; Nonalcoholic fatty liver disease; Stroke.

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Conflict of interest statement

Conflicts of Interest

AJS is 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, Astra Zeneca, Malinckrodt, Cumberland and Norvatis. He receives royalties from Elsevier and UptoDate. MN has been on the advisory board for 89BIO, Gilead, Intercept, Pfizer, Novo Nordisk, Blade, EchoSens, Fractyl, Terns, Siemens and Roche diagnostic; MN has received research support from Allergan, BMS, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Madrigal, Novartis, Pfizer, Shire, Viking and Zydus; MN is a minor shareholder or has stocks in Anaetos, Rivus Pharma and Viking.

All other authors do not have any conflict of interest to declare.

Figures

Figure 1.
Figure 1.
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart.
Figure 2.
Figure 2.
Forest plot on the odds of stroke in nonalcoholic fatty liver disease. OR, odds ratio; CI, confidence interval.
Figure 3.
Figure 3.
Prevalence of carotid atherosclerosis by geographical region.
None
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