ArticleGastroenterology2023
PNPLA3 Genotype and Diabetes Identify Patients With Nonalcoholic Fatty Liver Disease at High Risk of Incident Cirrhosis.
Article in Gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 6 of them syntheses that pooled it.
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Who cites it
64 citing papers in PubMed, 6 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- AGA Clinical Practice Update on Risk Stratification and Emerging Surveillance Strategies for Hepatocellular Carcinoma: Expert Review.Gastroenterology · 2026Guideline
- Impact of empagliflozin on liver fat reduction in type 2 diabetes and NAFLD: A systematic review and meta-analysis.Endocrine · 2026Pooled it
- Meta-Analysis: Effects of Steatotic Liver Disease-Associated Genetic Risk Alleles on Longitudinal Outcomes.Alimentary pharmacology & therapeutics · 2025Pooled it
- EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).Obesity facts · 2024Guideline
- A common variant that alters SUN1 degradation associates with hepatic steatosis and metabolic traits in multiple cohorts.Journal of hepatology · 2023Pooled it
- Type 2 diabetes, hepatic decompensation, and hepatocellular carcinoma in patients with non-alcoholic fatty liver disease: an individual participant-level data meta-analysis.The lancet. Gastroenterology & hepatology · 2023Pooled it
- Exercise training improves serum biomarkers of liver fibroinflammation in patients with metabolic dysfunction-associated steatohepatitis.Liver international : official journal of the International Association for the Study of the Liver · 2024Trial
- Genetics of MASLD: a diabetes perspective.Diabetologia · 2026Review
- Mild alkaline phosphatase elevation associates with increased mortality and major adverse liver outcomes in MASLD.Hepatology communications · 2026Article
- Large-Scale Plasma Proteomics Enhances Prediction of Liver-Related Events Among Individuals With Prediabetes and Type 2 Diabetes: A Prospective Cohort Study in the UK Biobank.Diabetes, obesity & metabolism · 2026Article
- Dietary one-carbon metabolism nutrients and risk of MASLD progression: a prospective cohort study.European journal of clinical nutrition · 2026Article
- Predictive modeling and clinical decision tools for risk stratification in steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Genetic and genomic insights across the steatotic liver disease spectrum.Clinical and molecular hepatology · 2026Review
- Article
- Impact of Air Pollution on Metabolic Dysfunction-Associated Fatty Liver Disease.International journal of molecular sciences · 2026Review
- Data-driven classification of metabolic-associated steatotic liver disease subtypes predicting hepatic and extrahepatic progression.Chinese medical journal · 2026Article
- LYPLAL1 rare loss-of-function variants in humans and deletion in human hepatoma cells protect against MASLD.Journal of lipid research · 2026Article
- From a Multi-Omics Signature to a Therapeutic Candidate: Computational Prediction and Experimental Validation in Liver Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Sarcopenia and MASLD: novel insights and the future.Nature reviews. Endocrinology · 2026Review
- Genome-wide association study identifies three PNPLA3/SAMM50 SNPs associated with HCC development in non-viral liver disease.JHEP reports : innovation in hepatology · 2026Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsNon-alcoholic fatty liver disease (NAFLD) can progress to cirrhosis and hepatic decompensation, but whether genetic variants influence the rate of progression to cirrhosis or are useful in risk stratification among patients with NAFLD is uncertain.
methodsWe included participants from 2 independent cohorts, they Michigan Genomics Initiative (MGI) and UK Biobank (UKBB), who had NAFLD defined by elevated alanine aminotransferase (ALT) levels in the absence of alternative chronic liver disease. The primary predictors were genetic variants and metabolic comorbidities associated with cirrhosis. We conducted time-to-event analyses using Fine-Gray competing risk models.
resultsWe included 7893 and 46,880 participants from MGI and UKBB, respectively. In univariable analysis, PNPLA3-rs738409-GG genotype, diabetes, obesity, and ALT of ≥2× upper limit of normal were associated with higher incidence rate of cirrhosis in both MGI and UKBB. PNPLA3-rs738409-GG had additive effects with clinical risk factors including diabetes, obesity, and ALT elevations. Among patients with indeterminate fibrosis-4 (FIB4) scores (1.3-2.67), those with diabetes and PNPLA3-rs738409-GG genotype had an incidence rate of cirrhosis comparable to that of patients with high-risk FIB4 scores (>2.67) and 2.9-4.8 times that of patients with diabetes but CC/CG genotypes. In contrast, FIB4 <1.3 was associated with an incidence rate of cirrhosis significantly lower than that of FIB4 of >2.67, even in the presence of clinical risk factors and high-risk PNPLA3 genotype.
conclusionsPNPLA3-rs738409 genotype and diabetes identified patients with NAFLD currently considered indeterminate risk (FIB4 1.3-2.67) who had a similar risk of cirrhosis as those considered high-risk (FIB4 >2.67). PNPLA3 genotyping may improve prognostication and allow for prioritization of intensive intervention.
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