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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 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]
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“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]
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Metadata
- 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 › Hepatology › 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
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