ReviewLiver international : official journal of the International Association for the Study of the Liver2025
Fifteen Years of PNPLA3: Transforming Hepatology Through Human Genetics.
Review in Liver international : official journal of the International Association for the Study of the Liver, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effects of Pioglitazone On Lipoprotein(a): A Meta-analysis.Current atherosclerosis reports · 2025Pooled it
- Metabolic Dysfunction-Associated Steatotic Disease and Genetic Risk in Germany-An Observational Real-World Cohort Study.United European gastroenterology journal · 2026Observational
- Steatotic liver disease in Latin America: current views and perspectives.Nature reviews. Gastroenterology & hepatology · 2026Review
- Correction to 'Fifteen Years of PNPLA3: Transforming Hepatology through Human Genetics'.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- α/β-Hydrolase Domain Containing 5 Supports Glucose-Stimulated Lipolysis and Insulin Secretion in Pancreatic β-Cells.Diabetes · 2026Article
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- Selenium and Liver Steatosis and Fibrosis: Opposing Direct and Steatosis-Mediated Associations in a Large Cohort.JGH open : an open access journal of gastroenterology and hepatology · 2026Article
- Influence of genetics on clinical trajectories in children with MASLD: role of the PNPLA3 I148M polymorphism.Journal of endocrinological investigation · 2026Observational
- Linked Intronic Polymorphisms of theInternational journal of molecular sciences · 2026Article
- Associations between diabetes mellitus and drinking patterns in Korean adults by sex: insights from the Korea National health and nutrition examination survey 2013-2018.Diabetology & metabolic syndrome · 2025Article
- Focus on Semaglutide 2.4 mg/week for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Metabolic Dysfunction-Associated Steatotic Liver Disease in a Patient with Phelan-McDermid Syndrome.Life (Basel, Switzerland) · 2025Article
- Fifteen Years of PNPLA3: Transforming Hepatology Through Human Genetics.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
2 authors.
Funding
Abstract
Steatotic liver disease (SLD), caused by excess lipid accumulation in hepatocytes, is now a leading global liver condition triggered by metabolic dysfunction, alcohol, toxins and heritable factors. The main genetic determinant is the common PNPLA3 p.I148M variant, which explains a substantial portion of SLD interindividual and interethnic variability, up to a quarter of liability to cirrhosis and liver cancer in the general population. Discovered in 2008 through genome-wide association studies, this variant increases the risk of liver steatosis, inflammation, fibrosis and the risk of complications as hepatocellular carcinoma. Carriers, particularly homozygotes, show higher susceptibility to liver damage, with the variant interacting with environmental factors such as increased adiposity, diet, insulin resistance and female sex. Experimental models indicate a complex mechanistic impact, involving lipid transfer and retinoid metabolism. Phase 1 clinical trials exploring PNPLA3 inhibitors, such as siRNA and antisense oligonucleotides, are promising, demonstrating up to 40% reductions in hepatic fat and inflammation in homozygous carriers. These advances suggest that targeting PNPLA3 can pave the way for precision medicine in hepatology. Overall, the discovery of PNPLA3's role has significantly enhanced understanding of liver steatosis, steatohepatitis and potential therapeutic interventions, highlighting its importance as a therapeutic target for SLD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.