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

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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 languageEnglish (US)
Pages (from-to)33-39
Number of pages7
JournalEndocrine Practice
Issue number1
StatePublished - Jan 2023


  • CVD
  • meta-analysis
  • mortality
  • 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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