ArticleAlimentary pharmacology & therapeutics2018
Impact of patatin-like phospholipase domain containing 3 rs738409 G/G genotype on hepatic decompensation and mortality in patients with portal hypertension.
Article in Alimentary pharmacology & therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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18 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Meta-Analysis: Effects of Steatotic Liver Disease-Associated Genetic Risk Alleles on Longitudinal Outcomes.Alimentary pharmacology & therapeutics · 2025Pooled it
- Noninvasive Tests for Predicting Decompensation in Compensated Advanced Chronic Liver Disease: A Comprehensive Review.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- The Alpha-1 Pi*MZ Genotype Is an Independent Risk Factor for Hepatocellular Carcinoma Development in Patients With ACLD.Alimentary pharmacology & therapeutics · 2026Article
- Targeting PNPLA3 to Treat MASH and MASH Related Fibrosis and Cirrhosis.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
- Compensated liver cirrhosis: Natural course and disease-modifying strategies.World journal of methodology · 2023Review
- PNPLA3 rs738409 risk genotype decouples TyG index from HOMA2-IR and intrahepatic lipid content.Cardiovascular diabetology · 2023Article
- Alpha-1 antitrypsin Pi∗Z allele is an independent risk factor for liver transplantation and death in patients with advanced chronic liver disease.JHEP reports : innovation in hepatology · 2022Article
- Impact of a Loss-of-Function Variant inInternational journal of molecular sciences · 2022Article
- Connection between HPS and ACLF: a solution of chaos?Hepatology international · 2021Article
- Combined effects of PNPLA3, TM6SF2 and HSD17B13 variants on severity of biopsy-proven non-alcoholic fatty liver disease.Hepatology international · 2021Article
- Influence of Genetic Variants on Disease Regression and Outcomes in HCV-Related Advanced Chronic Liver Disease after SVR.Journal of personalized medicine · 2021Article
- Recent Epidemiology of Nonalcoholic Fatty Liver Disease.Gut and liver · 2021Review
- Impact of HSD17B13 rs72613567 genotype on hepatic decompensation and mortality in patients with portal hypertension.Liver international : official journal of the International Association for the Study of the Liver · 2020Article
- Performance of Controlled Attenuation Parameter in Patients with Advanced Chronic Liver Disease and Portal Hypertension.Digestive diseases and sciences · 2019Article
- Impact of farnesoid X receptor single nucleotide polymorphisms on hepatic decompensation and mortality in cirrhotic patients with portal hypertension.Journal of gastroenterology and hepatology · 2019Article
- [Consensus on clinical application of hepatic venous pressure gradient in China (2018)].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2018Article
- Impact of patatin-like phospholipase domain containing 3 rs738409 G/G genotype on hepatic decompensation and mortality in patients with portal hypertension.Alimentary pharmacology & therapeutics · 2018Article
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13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe rs738409 C>G p.I148M variant in the patatin-like phospholipase domain containing 3 (PNPLA3)-gene promotes triglyceride accumulation in hepatocytes and hepatic stellate cell activation and has previously been linked to hepatic steatosis/liver fibrosis.
aimTo investigate its impact on hepatic decompensation and (liver-related) mortality in patients who had already developed portal hypertension. Moreover, we assessed its link with hepatic steatosis as evaluated by controlled attenuation parameter.
methodsWe performed a retrospective analysis in prospectively characterised patients with viral hepatitis/fatty liver disease-induced portal hypertension (hepatic venous pressure gradient [HVPG] ≥ 6 mm Hg) diagnosed at the Medical University of Vienna who underwent HVPG measurement (until 2013; n = 372; longitudinal study) or simultaneous HVPG and controlled attenuation parameter measurement (2014-2017; n = 153; cross-sectional study).
resultsWhile survival was similar between PNPLA3-C/C and -C/G patients, we observed substantially increased mortality in PNPLA3-G/G patients. PNPLA3-G/G had no impact on mortality in the subgroup of patients with viral hepatitis; however, we observed a strong independent association between PNPLA3-G/G and hepatic decompensation (adjusted subdistribution hazard ratio [aSHR]: 2.1, 95% confidence interval [95% CI]: 1.1-4; P = 0.024) as well as mortality (overall: aSHR: 2.2, 95% CI: 1.22-3.98; P = 0.009; liver-related: aSHR: 2.2, 95% CI: 1.08-4.46; P = 0.029) in patients with fatty liver disease. Interestingly, even in the subgroup of patients who had already progressed to clinically significant portal hypertension (HVPG ≥ 10 mm Hg), PNPLA3-G/G substantially increased mortality (aSHR: 2.33, 95% CI: 1.27-4.29; P = 0.006). PNPLA3-genotype had no influence on controlled attenuation parameter or the prevalence of values ≥248 dB/m.
conclusionPNPLA3-G/G-genotype seems to double the risks of hepatic decompensation and (liver-related) mortality in patients with portal hypertension due to fatty liver disease. Further studies are warranted to investigate potential underlying pathophysiological mechanisms unrelated to hepatic steatosis.
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