ArticleHepatology international2021
Combined effects of PNPLA3, TM6SF2 and HSD17B13 variants on severity of biopsy-proven non-alcoholic fatty liver disease.
Article in Hepatology international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- TM6SF2 rs58542926 is related to hepatic steatosis, fibrosis and serum lipids both in adults and children: A meta-analysis.Frontiers in endocrinology · 2022Pooled it
- Long-term ambient benzene exposure increases incident NAFLD risk through accelerated biological aging.iScience · 2026Article
- Nutriomic Technologies for Characterizing, Diagnosing, Clustering and Managing Chronic Liver Diseases: Precision Nutrition Implications.International journal of molecular sciences · 2026Review
- Inherited Genetic Risk of Liver Fibrosis in Lean Versus Nonlean Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).Alimentary pharmacology & therapeutics · 2026Article
- Mitochondrial dysfunction and lipid droplet dynamics in MASH: HSD17B13 as a therapeutic target.Frontiers in cell and developmental biology · 2026Review
- Identification of causal plasma proteins and targeted therapy for primary hepatic carcinoma via proteome-wide Mendelian randomization.Communications biology · 2025Article
- Genetic Risk of MASLD in Mongolians: Role ofCurrent issues in molecular biology · 2025Article
- Incretins and MASLD: at the Crossroads of Endocrine and Hepatic Disorders.Current obesity reports · 2025Review
- Impact of differential detection of TM6SF2 rs58542926 mutation in circulating tumor DNA versus peripheral blood cells on hepatocellular carcinoma patients.Discover oncology · 2025Article
- A comprehensive evaluation of candidate genetic polymorphisms in a large histologically characterized MASLD cohort using a novel framework.Hepatology communications · 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
- Exploring Biomarkers in Nonalcoholic Fatty Liver Disease Among Individuals With Type 2 Diabetes Mellitus.Journal of clinical gastroenterology · 2025Review
- TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD.Clinical and molecular hepatology · 2024Article
- Are we ready for genetic testing in metabolic dysfunction-associated steatotic liver disease?United European gastroenterology journal · 2024Review
- Metabolic liver cancer: associations of rare and common germline variants in one-carbon metabolism and DNA methylation genes.Human molecular genetics · 2023Article
- Single-Nucleotide Polymorphisms in Base-Excision Repair-Related Genes Involved in the Risk of an Occurrence of Non-Alcoholic Fatty Liver Disease.International journal of molecular sciences · 2023Article
- Discovery of a Novel Potent and Selective HSD17B13 Inhibitor, BI-3231, a Well-Characterized Chemical Probe Available for Open Science.Journal of medicinal chemistry · 2023Article
- Advances in genetic variation in metabolism-related fatty liver disease.Frontiers in genetics · 2023Review
- Review article: the role of HSD17B13 on global epidemiology, natural history, pathogenesis and treatment of NAFLD.Alimentary pharmacology & therapeutics · 2023Review
Corrections and comments
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Authors and funding
23 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveSeveral single-nucleotide polymorphisms have been identified to be disadvantageous or protective in regard to disease severity in patients with non-alcoholic fatty liver disease (NAFLD). However, it is unclear, whether including genetic risk factor(s) either alone or combined into risk stratification algorithms for NAFLD actually provides incremental benefit over clinical risk factors.
designPatients with biopsy-proven NAFLD were genotyped for the PNPLA3-rs738409(minor allele:G), TM6SF2-rs58542926(minor allele:T) and HSD17B13- rs72613567 (minor allele:TA) variants. The NAFLD activity score (NAS) and fibrosis stage (F0-F4) were used to grade and stage all liver biopsy samples. Patients from seven centers throughout Central Europe were considered for the study.
results703 patients were included: NAS ≥ 5:173(24.6%); Fibrosis: F3-4:81(11.5%). PNPLA3 G/G genotype was associated with a NAS ≥ 5(aOR 2.23, p = 0.007) and advanced fibrosis (aOR-3.48, p < 0.001).TM6SF2 T/- was associated with advanced fibrosis (aOR 1.99, p = 0.023). HSD17B13 TA/- was associated with a lower probability of NAS ≥ 5(TA/T: aOR 0.65, p = 0.041, TA/TA: aOR 0.40, p = 0.033). Regarding the predictive capability for NAS ≥ 5, well-known risk factors (age, sex, BMI, diabetes, and ALT; baseline model) had an AUC of 0.758, Addition of PNPLA3(AUC 0.766), HSB17B13(AUC 0.766), and their combination(AUC 0.775), but not of TM6SF2(AUC 0.762), resulted in a higher diagnostic accuracy of the model. Addition of genetic markers for the prediction of advanced fibrosis (baseline model: age, sex, BMI, diabetes: AUC 0.777) resulted in a higher AUC if PNPLA3(AUC 0.789), and TM6SF2(AUC 0.786) but not if HSD17B13(0.777) were added.
conclusionIn biopsy-proven NAFLD, PNPLA3 G/-, TM6SF2 T/- and HSD17B13 TA/- carriage are associated with severity of NAFLD. Incorporating these genetic risk factors into risk stratification models might improve their predictive accuracy for severity of NAFLD and/or advanced fibrosis on liver biopsy.
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