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

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          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.

          Conclusions

          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.

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          Most cited references107

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          Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range

          Background In systematic reviews and meta-analysis, researchers often pool the results of the sample mean and standard deviation from a set of similar clinical trials. A number of the trials, however, reported the study using the median, the minimum and maximum values, and/or the first and third quartiles. Hence, in order to combine results, one may have to estimate the sample mean and standard deviation for such trials. Methods In this paper, we propose to improve the existing literature in several directions. First, we show that the sample standard deviation estimation in Hozo et al.’s method (BMC Med Res Methodol 5:13, 2005) has some serious limitations and is always less satisfactory in practice. Inspired by this, we propose a new estimation method by incorporating the sample size. Second, we systematically study the sample mean and standard deviation estimation problem under several other interesting settings where the interquartile range is also available for the trials. Results We demonstrate the performance of the proposed methods through simulation studies for the three frequently encountered scenarios, respectively. For the first two scenarios, our method greatly improves existing methods and provides a nearly unbiased estimate of the true sample standard deviation for normal data and a slightly biased estimate for skewed data. For the third scenario, our method still performs very well for both normal data and skewed data. Furthermore, we compare the estimators of the sample mean and standard deviation under all three scenarios and present some suggestions on which scenario is preferred in real-world applications. Conclusions In this paper, we discuss different approximation methods in the estimation of the sample mean and standard deviation and propose some new estimation methods to improve the existing literature. We conclude our work with a summary table (an Excel spread sheet including all formulas) that serves as a comprehensive guidance for performing meta-analysis in different situations. Electronic supplementary material The online version of this article (doi:10.1186/1471-2288-14-135) contains supplementary material, which is available to authorized users.
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            The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases.

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              Meta-analysis in clinical trials.

              This paper examines eight published reviews each reporting results from several related trials. Each review pools the results from the relevant trials in order to evaluate the efficacy of a certain treatment for a specified medical condition. These reviews lack consistent assessment of homogeneity of treatment effect before pooling. We discuss a random effects approach to combining evidence from a series of experiments comparing two treatments. This approach incorporates the heterogeneity of effects in the analysis of the overall treatment efficacy. The model can be extended to include relevant covariates which would reduce the heterogeneity and allow for more specific therapeutic recommendations. We suggest a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.
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                Author and article information

                Journal
                Clin Mol Hepatol
                Clin Mol Hepatol
                CMH
                Clinical and Molecular Hepatology
                The Korean Association for the Study of the Liver
                2287-2728
                2287-285X
                July 2022
                2 March 2022
                : 28
                : 3
                : 483-496
                Affiliations
                [1 ]Yong Loo Lin School of Medicine, National University of Singapore, Singapore
                [2 ]Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
                [3 ]Bristol Medical School, University of Bristol, Bristol, UK
                [4 ]Division of Neurology, Department of Medicine, National University Hospital, Singapore
                [5 ]Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
                [6 ]National University Centre for Organ Transplantation, National University Health System, Singapore
                [7 ]Department of Cardiology, National University Heart Centre, National University Hospital, Singapore
                [8 ]Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
                Author notes
                Corresponding author : Cheng Han Ng Yong Loo Lin School of Medicine, National University of Singapore, Singapore 10 Medical Dr, Singapore 117597, Singapore Tel: +65 6772 3737, Fax: +65 6778 5743, E-mail: chenhanng@ 123456gmail.com
                Mark Muthiah Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore 119228, Singapore Tel: +65 6772 4354, Fax: +65 6775 1518, E-mail: mdcmdm@ 123456nus.edu.sg
                [*]

                These authors contributed equally to this work as co-first authors.

                Editor: Jian-Gao Fan, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, China

                Author information
                http://orcid.org/0000-0002-9724-4743
                http://orcid.org/0000-0002-8297-1569
                Article
                cmh-2021-0406
                10.3350/cmh.2021.0406
                9293613
                35232007
                8eaa63fc-2000-4e75-8a5d-4b7f45578c6e
                Copyright © 2022 by The Korean Association for the Study of the Liver

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 December 2021
                : 27 January 2022
                : 2 March 2022
                Categories
                Original Article

                Gastroenterology & Hepatology
                atherosclerosis,stroke,ischemic stroke,nonalcoholic fatty liver disease

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