Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review
Open accessAbstract
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) has been implicated as a cause of hepatocellular carcinoma (HCC). We performed a systematic review of epidemiology studies to confirm the association between these disorders. METHODS: We searched PubMed for original reports published from January 1992 to December 2011 that evaluated the association between NAFLD, nonalcoholic steatohepatitis (NASH), cryptogenic cirrhosis presumed to be NASH-related, and the risk of HCC. Studies were categorized as offering potential direct evidence (eg, cohort studies) or indirect evidence (eg, case-control, cross-sectional, or case-series studies) for an association. We analyzed data from a total of 17 cohort studies (3 population based, 9 clinic based [6 limited to patients with cirrhosis], and 5 natural history), 18 case-control and cross-sectional studies, and 26 case series. RESULTS: NAFLD or NASH cohorts with few or no cases of cirrhosis cases had a minimal risk for HCC (cumulative HCC mortality of 0%-3% for study periods up to 20 y). Cohorts with NASH and cirrhosis had a consistently higher risk (cumulative incidence ranging from 2.4% over 7 y to 12.8% over 3 y). However, the risk for HCC was substantially lower in these cohorts than for cohorts with hepatitis C-related cirrhosis. Factors that increased risk among cohorts with NASH and cirrhosis could not be determined, because most studies were not sufficiently powered for multivariate analysis. CONCLUSIONS: This systematic review shows that despite several limitations, there is epidemiologic evidence to support an association between NAFLD or NASH and an increased risk of HCC; risk seems to be limited to individuals with cirrhosis.
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A systematic review and a meta-analysis concluded that the risk estimate is likely too low to justify routine screening in MASLD without evidence of advanced fibrosis.
“A systematic review and a metaanalysis concluded that the risk estimate is likely too low to justify routine screening in MASLD without evidence of advanced fi brosis. 241”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [241]
The Discussion (page not provided) says the available data do not support routine HCC surveillance in general NAFLD/NASH cohorts without cirrhosis, supporting the screening conclusion for patients without advanced fibrosis. But the paper does not establish advanced fibrosis as the specific threshold, and the Discussion explicitly says it could not perform a meta-analysis. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe HCC incidence in individuals without cirrhosis is very low, ranging from 0.08 to 0.63 per 1,000 person-years.
“the HCC incidence in individuals without cirrhosis is very low, ranging from 0.08 to 0.63 per 1,000 PY. 240 -244”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [241]
The Results (Cohort studies; page not provided) describe no HCC cases in one NAFLD cohort without significant fibrosis and a low cumulative incidence in a larger NAFLD/NASH cohort. They do not report the claimed range of 0.08–0.63 per 1,000 person-years specifically for individuals without cirrhosis; the reported measures are cumulative incidence or mortality, and the cohorts are not consistently restricted to people without cirrhosis. (LLM, conf=0.86)
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- Authors
- White, D. L., Kanwal, F., & El–Serag, H. B.
- Affiliations
- Michael E. DeBakey VA Medical Center (US)
- Corresponding author
- White, Donna L.
- Venue
- Clinical Gastroenterology and Hepatology
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 10
- Issue
- 12
- Pages
- 1342-1359.e2
- ISSN
- 1542-3565 (ISSN-L)
- PMC
- PMC3501546
- OpenAlex
- W1975567145
- Cited by
- 766
- References
- 73
- Citations by year
- 2026: 16 · 2025: 26 · 2024: 39 · 2023: 49 · 2022: 61 · 2021: 71 · 2020: 68 · 2019: 64 · 2018: 76 · 2017: 73 · 2016: 54 · 2015: 58 · 2014: 54 · 2013: 56
- FWCI
- 6.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Clinical Gastroenterology and Hepatology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (HFP90-020, DK56338)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK56338, K24DK078154, K24 DK081736-01, K01 DK078154-03, K01DK081736, P30DK056338)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, hepatocellular carcinoma, liver cirrhosis, cryptogenic cirrhosis, cancer risk, HCC mortality
- MeSH terms
- Fatty Liver, Humans, Liver Neoplasms, Risk Assessment, Non-alcoholic Fatty Liver Disease
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 ›
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