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Cited by 176Liver Disease Diagnosis and TreatmentAlcohol Consumption and Health EffectsHealthcare Systems and Public Health

Nonalcoholic fatty liver disease and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis

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Liu, Yan, Zhong, Guo-Chao, Tan, Hao-Yang, Hao, Fa-Bao, Hu, Jie-Jun·2019·Scientific Reports
DOI 10.1038/s41598-019-47687-3PMC PMC6668400
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Abstract

Whether nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of mortality remains controversial. The present study aimed to clarify this issue. A systematic search of PubMed and Embase was conducted through October 2018. Studies providing risk estimates of NAFLD and mortality were included. A random-effects model was employed to calculate summary risk estimates. Subgroup analyses were performed to identify potential effect modifiers. Fourteen studies, involving 498501 subjects and 24234 deaths, were included. Patients with NAFLD were found to be at an elevated risk of all-cause mortality compared with those without [hazard ratio (HR) = 1.34; 95% confidence interval (CI) 1.17–1.54)]. The significantly positive association between NAFLD and all-cause mortality could not be modified by age, sex, follow-up duration, and adjustment for body mass index, diabetes, smoking or hypertension (all Pinteraction > 0.05), and remained in sensitivity analyses. No significant associations of NAFLD with CVD (HR = 1.13; 95% CI 0.92–1.38) and cancer (HR = 1.05; 95% CI 0.89–1.25) mortality were found. In conclusion, NAFLD is a predictor of increased all-cause mortality but not CVD and cancer mortality. These findings have important implications for decision making in public health and clinical practice, and highlight the urgency of developing effective treatments for NAFLD.

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  • MASLD may be associated with an increased risk of extrahepatic outcomes (HR 1.34).

    “it may be associated with an increased risk of extrahepatic outcomes (hazard ratio [HR] 1.34), 24”

    From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [24]

    Table 2 in the Results reports HR 1.34 (95% CI 1.17–1.54) for all-cause mortality in people with NAFLD. It does not report that estimate for extrahepatic outcomes specifically; all-cause mortality includes liver-related deaths, and the paper uses NAFLD rather than MASLD. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

  • Some studies indicated a higher risk of cardiovascular disease-related mortality (HR 1.30), while others did not confirm this result in the general population, but only in those with biopsy-proven MASH or other risk factors like T2D.

    “Although some studies indicated a higher risk of cardiovascular disease-related mortality (HR 1.30), 25,26 others did not con fi rm this result in the general population, but only in those with biopsy-proven MASH 24 or other risk factors like T2D. 15”

    From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [24]

    The Results (NAFLD and CVD mortality; page unavailable) find no significant overall association with CVD mortality (HR 1.13, 95% CI 0.92–1.38). The Discussion says a subgroup analysis suggested increased CVD mortality only with NASH, but explicitly calls that finding uncertain because it rests on few studies; it does not establish a biopsy-proven MASH-only effect. The HR 1.30 and T2D clauses have separate citations in the citing sentence, so they are not attributed to this source. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • In the general population, MASLD is not associated with increased overall cancer-related mortality.

    “In the general population, MASLD is not associated with increased overall cancer-related mortality, 24”

    From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [24]

    The Results (NAFLD and cancer mortality; page not provided) report no statistically significant association with overall cancer mortality (HR 1.05, 95% CI 0.89–1.25). The paper studies NAFLD, not MASLD, and its Study characteristics and quality assessment section says that although most participants came from the general population, some studies recruited people with specific conditions. It therefore does not directly establish the claim specifically for MASLD in the general population. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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References 36 · Cited by 176

Research works printed but not linked: 31

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Authors
Liu, Y., Zhong, G.-C., Tan, H.-Y., Hao, F.-B., & Hu, J.-J.
Affiliations
  • Chengdu Fifth People's Hospital (CN)
  • Second Affiliated Hospital of Chongqing Medical University (CN)
  • Qingdao University (CN)
Corresponding author
Zhong, Guo-Chao
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2019-07-31
Volume
9
Issue
1
Pages
11124-11124
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-019-47687-3
PMC
PMC6668400
OpenAlex
W2964628031
Cited by
176
References
36
Citations by year
2026: 11 · 2025: 29 · 2024: 28 · 2023: 28 · 2022: 28 · 2021: 33 · 2020: 16 · 2019: 2
FWCI
2.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Sichuan Applied Basic Research Projec
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Health Sciences › Medicine › Epidemiology › Healthcare Systems and Public Health
Keywords
non-alcoholic fatty liver disease, all-cause mortality, cardiovascular mortality, cancer mortality, mortality risk, effect modifiers, body mass index, diabetes mellitus
MeSH terms
Adult, Aged, Aged, 80 and over, Cardiovascular Diseases, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasms, Risk Factors, Young Adult, Observational Studies as Topic, Non-alcoholic Fatty Liver Disease

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