CoChat
Sign Up
Cited by 56Liver Disease Diagnosis and TreatmentAlcohol Consumption and Health EffectsLiver Diseases and Immunity

Hepatic, extra-hepatic outcomes and causes of mortality in NAFLD - an umbrella overview of systematic review of meta-analysis

Open access
Xiao, Jieling, Ng, Cheng Han, Chan, Kai En, Fu, Clarissa, Tay, Phoebe, Yong, Jie Ning, Lim, Wen Hui, Tan, Darren Jun Hao +12 more·2023·Journal of Clinical and Experimental Hepatology
DOI 10.1016/j.jceh.2022.11.006PMC PMC10333954
Open this paper in CoChat — free accountOpen PDF

Abstract

Background Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease globally. While the prevalence, impact, and causes of mortality have been described in various meta-analyses, a systematic all-encompassing umbrella review has yet to be conducted to consolidate the evidence on outcomes associated with NAFLD.Methods Search was conducted on Medline and Embase for meta-analysis investigating associated complications and causes of mortality in NAFLD patients. Summary estimates were presented with original units, sample size, and I 2 for heterogeneity. The Assessment of Multiple Systematic Reviews 2 was employed for article selection.Results 25 meta-analyses were included in the present review. NAFLD increased the risks of systemic complications, including cardiovascular diseases, systemic malignancies, diabetes, and chronic kidney disease. Regarding hepatic outcomes, the incidence of hepatocellular carcinoma in NAFLD was 2.39 per 100 person years (CI: 1.40 to 4.08). Individuals with NAFLD were also found to have an increased likelihood of cholangiocarcinoma (OR: 1.88, CI: 1.25 to 2.83) and gallstone disease (OR: 1.55, CI: 1.31 to 1.82) compared to individuals without NAFLD. NAFLD was associated with a higher risk of fatal and non-fatal CVD events (HR: 1.45, CI: 1.31 to 1.61) compared to individuals without NAFLD. Coronary heart disease and subclinical and clinical coronary heart disease were also significantly elevated in NAFLD individuals compared to individuals without NAFLD. Additionally, NAFLD was associated with an increased risk of all-cause mortality (HR: 1.34, CI: 1.17 to 1.54) and cardiovascular (HR: 1.30, CI: 1.08 to 1.56) but not cancer-related mortality.Conclusion The study summarizes high-level evidence from published meta-analyses to provide a much-needed update on the outcomes in patients with NAFLD. The significant systemic burden associated with NAFLD and impending fatty liver epidemic requires prompt action from multidisciplinary providers, policy providers, and stakeholders to reduce the burden of NAFLD.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.jceh.2022.11.006

Cites

69 of 69 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Individuals with MASLD have a higher risk of diabetes-related peripheral polyneuropathy (HR 2.48).

    “T2D and diabetes-related peripheral polyneuropathy (HRs 2.19 and 2.48, respectively)”

    From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [26]

    The Other Complications and Associated Measurements section reports increased diabetes risk with NAFLD (HR 2.19), supporting the T2D portion of the citing sentence. It gives 2.48 as the upper confidence limit for diabetes, not as a hazard ratio for peripheral diabetic polyneuropathy; the References section lists a polyneuropathy meta-analysis, but the retrieved text provides no HR for that outcome. The paper studies NAFLD rather than explicitly defining its population as MASLD. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

  • Individuals with MASLD have a higher risk of chronic kidney disease (HR 1.43).

    “chronic kidney disease (HR 1.43)”

    From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [26]

    The ‘Other Complications and Associated Measurements’ section reports a higher risk of chronic kidney disease (HR 1.43) in people with NAFLD than in those without NAFLD. The claim gives the correct outcome and estimate but applies them to MASLD, a term and population the cited passage does not establish as equivalent. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Individuals with MASLD have a higher risk of obstructive sleep apnoea (OSA, HR 2.22).

    “obstructive sleep apnoea (OSA, HR 2.22). 26”

    From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [26]

    The Figure 5 legend identifies OSA among the complications examined in people with NAFLD, supporting the general association. But the available text does not state that OSA risk is higher by HR 2.22; it also studies NAFLD rather than explicitly defining a MASLD population. No page number is available in our copy. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Individuals with MASLD have a higher risk of T2D (HR 2.19).

    “T2D and diabetes-related peripheral polyneuropathy (HRs 2.19 and 2.48, respectively)”

    From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [26]

    The ‘Other Complications and Associated Measurements’ section reports a higher risk of diabetes with HR 2.19, but the comparison is between people with and without NAFLD. It does not establish that this estimate applies specifically to MASLD or identify the outcome as type 2 diabetes. (LLM, conf=0.86)

    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 [26]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

2 of the 71 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Xiao, J., Ng, C. H., Chan, K. E., Fu, C., Tay, P., Yong, J. N., Lim, W. H., Tan, D. J. H., Syn, N., Wong, Z. Y., Tseng, M., Chew, N., Huang, D. Q., Dan, Y. Y., Wong, V. W.-S., Loomba, R., Siddiqui, M. S., Sanyal, A. J., Noureddin, M., & Muthiah, M. D.
Affiliations
  • National University of Singapore (SG)
  • IMU University (MY)
  • Virginia Commonwealth University (US)
  • National University Heart Centre Singapore (SG)
  • Chinese University of Hong Kong (HK)
  • University of California San Diego (US)
Corresponding author
  • Ng, Cheng Han
  • Muthiah, Mark D.
ORCID
Venue
Journal of Clinical and Experimental Hepatology
Publisher
Elsevier BV
Published
2023-07
Volume
13
Issue
4
Pages
656-665
ISSN
0973-6883 (ISSN-L)
DOI
10.1016/j.jceh.2022.11.006
PMC
PMC10333954
OpenAlex
W4309482173
Cited by
56
References
71
Citations by year
2026: 8 · 2025: 19 · 2024: 19 · 2023: 9 · 2022: 1
FWCI
1.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Clinical and Experimental Hepatology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (P01HL147835)
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 › Hepatology › Liver Diseases and Immunity
Keywords
non-alcoholic fatty liver disease, mortality, cardiovascular disease, hepatocellular carcinoma, cholangiocarcinoma, gallstone disease, diabetes mellitus, chronic kidney disease, cancer risk, all-cause mortality, coronary artery disease, systemic complications

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review