ArticleClinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association2024
PNPLA3, Obesity, and Heavy Alcohol Use in Cirrhosis Patients May Exert a Synergistic Increase Hepatocellular Carcinoma Risk.
Article in Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-Analysis: Effects of Steatotic Liver Disease-Associated Genetic Risk Alleles on Longitudinal Outcomes.Alimentary pharmacology & therapeutics · 2025Pooled it
- Genetic and genomic insights across the steatotic liver disease spectrum.Clinical and molecular hepatology · 2026Review
- Rare Germline Variants in Key Pathways Contribute to Hepatocellular Carcinoma Risk in Hispanic Individuals.Cancers · 2026Article
- Exposure to Poly- and Perfluoroalkyl Substances and Risk of Hepatocellular Carcinoma in Male Patients with Cirrhosis Related to Hepatitis C Virus Infection.Liver cancer · 2026Article
- Risk Factors for Hepatocellular Carcinoma in Latino Populations in Texas: A Scoping Review.International journal of molecular sciences · 2026Article
- Rab5 nucleotide binding promotes oxidative metabolism to fuel hepatocellular carcinoma cell proliferation.The Journal of biological chemistry · 2026Article
- PNPLA3 I148M is unrelated to HCC occurrence but associates with poorer tumor differentiation in Korean MASLD: a prospective cohort of 562 patients.Journal of liver cancer · 2026Article
- MiR-18a-5p Attenuates Oxidative Stress and Inhibits Lipid Accumulation in Alcoholic Fatty Liver by Activating the CYP1A1-PPAR Axis.Immunity, inflammation and disease · 2026Article
- Integrated Bioinformatics Analysis Revealing that the NSDHL Gene Might Be Associated with the Progression of Western HFD/SW-Induced Hepatocellular CarcinomaEndocrine, metabolic & immune disorders drug targets · 2026Article
- Review
- Bridging the gap in obesity research: A consensus statement from the European Society for Clinical Investigation.European journal of clinical investigation · 2025Review
- High-Risk PNPLA3 rs738409 Genotype Is Associated with Higher Concentrations of CCL2 in Liver Transplant Candidates with Alcoholic End-Stage Liver Disease.Medicina (Kaunas, Lithuania) · 2025Article
- Integrating PNPLA3 into clinical risk prediction.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Correlation between body mass index and lymph node metastasis in papillary thyroid carcinoma: a retrospective clinical study.Gland surgery · 2024Article
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10 authors.
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Abstract
BACKGROUND &
aimsIn patients with cirrhosis, continued heavy alcohol consumption and obesity may increase risk of hepatocellular carcinoma (HCC). We examined whether germline susceptibility to hepatic steatosis not only independently predisposes to HCC but may also act synergistically with other risk factors.
methodsWe analyzed data from 1911 patients in 2 multicenter prospective cohort studies in the United States. We classified patients according to alcohol consumption (current heavy vs not current heavy), obesity (body mass index ≥30 vs <30 kg/m2), and PNPLA3 I148M variant status (carrier of at least one G risk allele vs noncarrier). We examined the independent and joint effects of these risk factors on risk of developing HCC using Cox regression with competing risks.
resultsMean age was 59.6 years, 64.3% were male, 28.7% were Hispanic, 18.3% were non-Hispanic Black, 50.9% were obese, 6.2% had current heavy alcohol consumption, and 58.4% harbored at least 1 PNPLA3 G-allele. One hundred sixteen patients developed HCC. Compared with PNPLA3 noncarriers without heavy alcohol consumption, HCC risk was 2.65-fold higher (hazard ratio [HR], 2.65; 95% confidence interval [CI], 1.20-5.86) for carriers who had current heavy alcohol consumption. Compared with noncarrier patients without obesity, HCC risk was higher (HR, 2.40; 95% CI, 1.33-4.31) for carrier patients who were obese. PNPLA3 and alcohol consumption effect was stronger among patients with viral etiology of cirrhosis (HR, 3.42; 95% CI, 1.31-8.90). PNPLA3 improved 1-year risk prediction for HCC when added to a clinical risk model.
conclusionsThe PNPLA3 variant may help refine risk stratification for HCC in patients with cirrhosis with heavy alcohol consumption or obesity who may need specific preventive measures.
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