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

Clarissa Elysia Fu; Cheng Han Ng; Jie Ning Yong; Kai En Chan; Jieling Xiao; Benjamin Nah; Shirley Huey Shin Bong; Khin Maung Win; Aung Hlaing Bwa; Wen Hui Lim; Darren Jun Hao Tan; Rebecca Wenling Zeng; Nicholas Chew; Margaret L.P. Teng; Mohammad Shadab Siddiqui; Jude A. Oben; Arun J. Sanyal; Vincent Wai Sun Wong; Mazen Noureddin; Mark Muthiah

doi:10.1016/j.eprac.2022.10.007

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

Clarissa Elysia Fu, Cheng Han Ng, Jie Ning Yong, Kai En Chan, Jieling Xiao, Benjamin Nah, Shirley Huey Shin Bong, Khin Maung Win, Aung Hlaing Bwa, Wen Hui Lim, Darren Jun Hao Tan, Rebecca Wenling Zeng, Nicholas Chew, Margaret L.P. Teng, Mohammad Shadab Siddiqui, Jude A. Oben, Arun J. Sanyal, Vincent Wai Sun Wong, Mazen Noureddin, Mark Muthiah

Houston Methodist

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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; I 2 = 96.00%), CVD-related mortality (HR, 1.22; 95% CI, 1.06-1.41; P < .01; I 2 = 81.00%), and cancer-related mortality (HR, 1.67; 95% CI, 1.15-2.41; P < .01; I 2 = 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; I 2 = 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.

Original language	English (US)
Pages (from-to)	33-39
Number of pages	7
Journal	Endocrine Practice
Volume	29
Issue number	1
DOIs	https://doi.org/10.1016/j.eprac.2022.10.007
State	Published - Jan 2023

Keywords

CVD
meta-analysis
mortality
NAFLD
Prevalence
Cardiovascular Diseases/complications
Humans
Risk Factors
Neoplasms/complications
Non-alcoholic Fatty Liver Disease/complications

ASJC Scopus subject areas

Endocrinology
Endocrinology, Diabetes and Metabolism

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10.1016/j.eprac.2022.10.007

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Fu, C. E., Ng, C. H., Yong, J. N., Chan, K. E., Xiao, J., Nah, B., Bong, S. H. S., Win, K. M., Bwa, A. H., Lim, W. H., Tan, D. J. H., Zeng, R. W., Chew, N., Teng, M. L. P., Siddiqui, M. S., Oben, J. A., Sanyal, A. J., Wong, V. W. S., Noureddin, M., & Muthiah, M. (2023). A Meta-analysis on Associated Risk of Mortality in Nonalcoholic Fatty Liver Disease. Endocrine Practice, 29(1), 33-39. https://doi.org/10.1016/j.eprac.2022.10.007

Fu, CE, Ng, CH, Yong, JN, Chan, KE, Xiao, J, Nah, B, Bong, SHS, Win, KM, Bwa, AH, Lim, WH, Tan, DJH, Zeng, RW, Chew, N, Teng, MLP, Siddiqui, MS, Oben, JA, Sanyal, AJ, Wong, VWS, Noureddin, M & Muthiah, M 2023, 'A Meta-analysis on Associated Risk of Mortality in Nonalcoholic Fatty Liver Disease', Endocrine Practice, vol. 29, no. 1, pp. 33-39. https://doi.org/10.1016/j.eprac.2022.10.007

@article{7ff3542debca4d598bccdf00b0077f69,

title = "A Meta-analysis on Associated Risk of Mortality in Nonalcoholic Fatty Liver Disease",

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; I 2 = 96.00%), CVD-related mortality (HR, 1.22; 95% CI, 1.06-1.41; P < .01; I 2 = 81.00%), and cancer-related mortality (HR, 1.67; 95% CI, 1.15-2.41; P < .01; I 2 = 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; I 2 = 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, meta-analysis, mortality, NAFLD, Prevalence, Cardiovascular Diseases/complications, Humans, Risk Factors, Neoplasms/complications, Non-alcoholic Fatty Liver Disease/complications",

author = "Fu, {Clarissa Elysia} and Ng, {Cheng Han} and Yong, {Jie Ning} and Chan, {Kai En} and Jieling Xiao and Benjamin Nah and Bong, {Shirley Huey Shin} and Win, {Khin Maung} and Bwa, {Aung Hlaing} and Lim, {Wen Hui} and Tan, {Darren Jun Hao} and Zeng, {Rebecca Wenling} and Nicholas Chew and Teng, {Margaret L.P.} and Siddiqui, {Mohammad Shadab} and Oben, {Jude A.} and Sanyal, {Arun J.} and Wong, {Vincent Wai Sun} and Mazen Noureddin and Mark Muthiah",

note = "Funding Information: 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. Funding Information: 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. Publisher Copyright: {\textcopyright} 2022 AACE",

year = "2023",

month = jan,

doi = "10.1016/j.eprac.2022.10.007",

language = "English (US)",

volume = "29",

pages = "33--39",

journal = "Endocrine Practice",

issn = "1530-891X",

publisher = "American Association of Clinical Endocrinology",

number = "1",

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TY - JOUR

T1 - A Meta-analysis on Associated Risk of Mortality in Nonalcoholic Fatty Liver Disease

AU - Fu, Clarissa Elysia

AU - Ng, Cheng Han

AU - Yong, Jie Ning

AU - Chan, Kai En

AU - Xiao, Jieling

AU - Nah, Benjamin

AU - Bong, Shirley Huey Shin

AU - Win, Khin Maung

AU - Bwa, Aung Hlaing

AU - Lim, Wen Hui

AU - Tan, Darren Jun Hao

AU - Zeng, Rebecca Wenling

AU - Chew, Nicholas

AU - Teng, Margaret L.P.

AU - Siddiqui, Mohammad Shadab

AU - Oben, Jude A.

AU - Sanyal, Arun J.

AU - Wong, Vincent Wai Sun

AU - Noureddin, Mazen

AU - Muthiah, Mark

N1 - Funding Information: 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. Funding Information: 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. Publisher Copyright: © 2022 AACE

PY - 2023/1

Y1 - 2023/1

N2 - 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; I 2 = 96.00%), CVD-related mortality (HR, 1.22; 95% CI, 1.06-1.41; P < .01; I 2 = 81.00%), and cancer-related mortality (HR, 1.67; 95% CI, 1.15-2.41; P < .01; I 2 = 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; I 2 = 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.

AB - 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; I 2 = 96.00%), CVD-related mortality (HR, 1.22; 95% CI, 1.06-1.41; P < .01; I 2 = 81.00%), and cancer-related mortality (HR, 1.67; 95% CI, 1.15-2.41; P < .01; I 2 = 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; I 2 = 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.

KW - CVD

KW - meta-analysis

KW - mortality

KW - NAFLD

KW - Prevalence

KW - Cardiovascular Diseases/complications

KW - Humans

KW - Risk Factors

KW - Neoplasms/complications

KW - Non-alcoholic Fatty Liver Disease/complications

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DO - 10.1016/j.eprac.2022.10.007

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SN - 1530-891X

VL - 29

SP - 33

EP - 39

JO - Endocrine Practice

JF - Endocrine Practice

IS - 1

ER -

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

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