ArticleLiver international : official journal of the International Association for the Study of the Liver2022
Effect of common genetic variants on the risk of cirrhosis in non-alcoholic fatty liver disease during 20 years of follow-up.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 3 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 3 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- Meta-Analysis of Genetic Variants Associated With HBV Infection Susceptibility and Hepatocellular Carcinoma Risk.Journal of viral hepatitis · 2026Pooled it
- Meta-Analysis: Effects of Steatotic Liver Disease-Associated Genetic Risk Alleles on Longitudinal Outcomes.Alimentary pharmacology & therapeutics · 2025Pooled it
- Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis.BMC medicine · 2024Pooled it
- PNPLA3 polymorphisms and risk of hepatic and extrahepatic outcomes in MASLD: A meta-analysis of observational studies.JHEP reports : innovation in hepatology · 2026Article
- Interactions between lipid droplets and mitochondria in metabolic diseases.Lipids in health and disease · 2025Review
- Clinical and Genetic Predictors of Non-Alcoholic Steatotic Liver Disease and Fibrosis in Lean Individuals.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Intestinal Depletion of TM6SF2 Exacerbates High-fat Diet-induced Metabolic Dysfunction-associated Steatotic Liver Disease through the Gut-liver Axis.Journal of clinical and translational hepatology · 2025Article
- Early childhood adiposity, lifestyle and gut microbiome are linked to steatotic liver disease development in adolescents.International journal of obesity (2005) · 2025Article
- Genetic predisposition of metabolic dysfunction-associated steatotic liver disease: a population-based genome-wide association study.Hepatology international · 2025Article
- Impact of PNPLA3 I148M on Clinical Outcomes in Patients With MASLD.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Integrating PNPLA3 into clinical risk prediction.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Data-driven cluster analysis identifies distinct types of metabolic dysfunction-associated steatotic liver disease.Nature medicine · 2024Article
- Review
- Insulin resistance is an integral feature of MASLD even in the presence of PNPLA3 variants.JHEP reports : innovation in hepatology · 2024Article
- Are we ready for genetic testing in metabolic dysfunction-associated steatotic liver disease?United European gastroenterology journal · 2024Review
- An integrated gene-to-outcome multimodal database for metabolic dysfunction-associated steatotic liver disease.Nature medicine · 2023Article
- Higher mortality among lean patients with non-alcoholic fatty liver disease despite fewer metabolic comorbidities.Alimentary pharmacology & therapeutics · 2023Article
- Screening for NAFLD-Current Knowledge and Challenges.Metabolites · 2023Review
- Glucokinase regulatory protein: a balancing act between glucose and lipid metabolism in NAFLD.Frontiers in endocrinology · 2023Review
- Development of LXR inverse agonists to treat MAFLD, NASH, and other metabolic diseases.Frontiers in medicine · 2023Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsSeveral genotypes associate with a worse histopathological profile in patients with non-alcoholic fatty liver disease (NAFLD). Whether genotypes impact long-term outcomes is unclear. We investigated the importance of PNPLA3, TM6SF2, MBOAT7 and GCKR genotype for the development of severe outcomes in NAFLD.
methodDNA samples were collected from 546 patients with NAFLD. Advanced fibrosis was diagnosed by liver biopsy or elastography. Non-alcoholic steatohepatitis (NASH) was histologically defined. Additionally, 5396 controls matched for age, sex and municipality were identified from population-based registers. Events of severe liver disease and all-cause mortality were collected from national registries. Hazard ratios (HRs) adjusted for age, sex, body mass index and type 2 diabetes were estimated with Cox regression.
resultsIn NAFLD, the G/G genotype of PNPLA3 was associated with a higher prevalence of NASH at baseline (odds ratio [OR] 3.67, 95% CI = 1.66-8.08), but not with advanced fibrosis (OR 1.81, 95% CI = 0.79-4.14). After up to 40 years of follow-up, the PNPLA3 G/G genotype was associated with a higher rate of severe liver disease (adjusted hazard ratio [aHR] 2.27, 95% CI = 1.15-4.47) compared with the C/C variant. NAFLD patients developed cirrhosis at a higher rate than controls (aHR 9.00, 95% CI = 6.85-11.83). The PNPLA3 G/G genotype accentuated this rate (aHR 23.32, 95% = CI 9.14-59.47). Overall mortality was not affected by any genetic variant.
conclusionThe PNPLA3 G/G genotype is associated with an increased rate of cirrhosis in NAFLD. Our results suggest that assessment of the PNPLA3 genotype is of clinical relevance in patients with NAFLD to individualize monitoring and therapeutic strategies.
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