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PNPLA3 risk allele is associated with risk of hepatocellular carcinoma but not decompensation in compensated cirrhosis.

Urias, E ; Tedesco, NR ; et al.
In: Hepatology communications, Jg. 8 (2024-05-22), Heft 6
Online academicJournal

Titel:
PNPLA3 risk allele is associated with risk of hepatocellular carcinoma but not decompensation in compensated cirrhosis.
Autor/in / Beteiligte Person: Urias, E ; Tedesco, NR ; Burkholder, DA ; Moran, IJ ; Miller, MJ ; Jasty, VSJ ; Patil, S ; Zoellner, S ; Wijarnpreecha, K ; Chen, VL
Link:
Zeitschrift: Hepatology communications, Jg. 8 (2024-05-22), Heft 6
Veröffentlichung: 2023- : [Philadelphia] : Wolters Kluwer Health, Inc. ; <i>Original Publication</i>: [Hoboken, NJ] : Wiley Periodicals, Inc. on behalf of the American Association for the Study of Liver Diseases, [2017]-, 2024
Medientyp: academicJournal
ISSN: 2471-254X (electronic)
DOI: 10.1097/HC9.0000000000000441
Schlagwort:
  • Humans
  • Male
  • Female
  • Middle Aged
  • Retrospective Studies
  • Aged
  • 17-Hydroxysteroid Dehydrogenases genetics
  • Genotype
  • Liver Transplantation
  • Polymorphism, Single Nucleotide
  • Genetic Predisposition to Disease
  • Risk Factors
  • Acyltransferases
  • Phospholipases A2, Calcium-Independent
  • Carcinoma, Hepatocellular genetics
  • Carcinoma, Hepatocellular mortality
  • Liver Neoplasms genetics
  • Liver Neoplasms mortality
  • Lipase genetics
  • Liver Cirrhosis genetics
  • Liver Cirrhosis complications
  • Liver Cirrhosis mortality
  • Membrane Proteins genetics
  • Alleles
Sonstiges:
  • Nachgewiesen in: MEDLINE
  • Sprachen: English
  • Publication Type: Journal Article
  • Language: English
  • [Hepatol Commun] 2024 May 22; Vol. 8 (6). <i>Date of Electronic Publication: </i>2024 May 22 (<i>Print Publication: </i>2024).
  • MeSH Terms: Carcinoma, Hepatocellular* / genetics ; Carcinoma, Hepatocellular* / mortality ; Liver Neoplasms* / genetics ; Liver Neoplasms* / mortality ; Lipase* / genetics ; Liver Cirrhosis* / genetics ; Liver Cirrhosis* / complications ; Liver Cirrhosis* / mortality ; Membrane Proteins* / genetics ; Alleles* ; Humans ; Male ; Female ; Middle Aged ; Retrospective Studies ; Aged ; 17-Hydroxysteroid Dehydrogenases / genetics ; Genotype ; Liver Transplantation ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; Risk Factors ; Acyltransferases ; Phospholipases A2, Calcium-Independent
  • References: Global health estimates: Leading causes of death. In: The Global Health Observatory. WHO; 2023. ; D’Amico G, Pasta L, Morabito A, D’Amico M, Caltagirone M, Malizia G, et al. Competing risks and prognostic stages of cirrhosis: A 25-year inception cohort study of 494 patients. Aliment Pharmacol Ther. 2014;39:1180–93. ; Fleming KM, Aithal GP, Card TR, West J. The rate of decompensation and clinical progression of disease in people with cirrhosis: A cohort study. Aliment Pharmacol Ther. 2010;32:1343–50. ; Kanwal F, Khaderi S, Singal AG, Marrero JA, Loo N, Asrani SK, et al. Risk factors for HCC in contemporary cohorts of patients with cirrhosis. Hepatology. 2023;77:997–1005. ; D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies. J Hepatol. 2006;44:217–31. ; Kim HS, Xiao X, Byun J, Jun G, DeSantis SM, Chen H, et al. Synergistic associations of PNPLA3 I148M variant, alcohol intake, and obesity with risk of cirrhosis, hepatocellular carcinoma, and mortality. JAMA Netw Open. 2022;5:e2234221. ; Trepo E, Caruso S, Yang J, Imbeaud S, Couchy G, Bayard Q, et al. Common genetic variation in alcohol-related hepatocellular carcinoma: A case-control genome-wide association study. Lancet Oncol. 2022;23:161–71. ; Abul-Husn NS, Cheng X, Li AH, Xin Y, Schurmann C, Stevis P, et al. A protein-truncating HSD17B13 variant and protection from chronic liver disease. N Engl J Med. 2018;378:1096–106. ; Buch S, Stickel F, Trepo E, Way M, Herrmann A, Nischalke HD, et al. A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis. Nat Genet. 2015;47:1443–8. ; Ma Y, Belyaeva OV, Brown PM, Fujita K, Valles K, Karki S, et al. 17-Beta hydroxysteroid dehydrogenase 13 is a hepatic retinol dehydrogenase associated with histological features of nonalcoholic fatty liver disease. Hepatology. 2019;69:1504–19. ; Chen VL, Chen Y, Du X, Handelman SK, Speliotes EK. Genetic variants that associate with cirrhosis have pleiotropic effects on human traits. Liver Int. 2020;40:405–15. ; Chen VL, Oliveri A, Miller MJ, Wijarnpreecha K, Du X, Chen Y, et al. PNPLA3 genotype and diabetes identify patients with nonalcoholic fatty liver disease at high risk of incident cirrhosis. Gastroenterology. 2023;164:966–77 e917. ; Gellert-Kristensen H, Richardson TG, Davey Smith G, Nordestgaard BG, Tybjaerg-Hansen A, Stender S. Combined effect of PNPLA3, TM6SF2, and HSD17B13 variants on risk of cirrhosis and hepatocellular carcinoma in the general population. Hepatology. 2020;72:845–56. ; Guyot E, Sutton A, Rufat P, Laguillier C, Mansouri A, Moreau R, et al. PNPLA3 rs738409, hepatocellular carcinoma occurrence and risk model prediction in patients with cirrhosis. J Hepatol. 2013;58:312–8. ; Balcar L, Scheiner B, Urheu M, Weinberger P, Paternostro R, Simbrunner B, et al. The impact of transmembrane 6 superfamily 2 (TM6SF2) rs58542926 on liver-related events in patients with advanced chronic liver disease. Dig Liver Dis. 2023;55:1072–80. ; Gil-Gomez A, Rojas A, Garcia-Lozano MR, Munoz-Hernandez R, Gallego-Duran R, Maya-Miles D, et al. Impact of a loss-of-function variant in HSD17B13 on hepatic decompensation and mortality in cirrhotic patients. Int J Mol Sci. 2022;23:11840. ; Dey R, Schmidt EM, Abecasis GR, Lee S. A fast and accurate algorithm to test for binary phenotypes and its application to PheWAS. Am J Hum Genet. 2017;101:37–49. ; Chen VL, Du X, Chen Y, Kuppa A, Handelman SK, Vohnoutka RB, et al. Genome-wide association study of serum liver enzymes implicates diverse metabolic and liver pathology. Nat Commun. 2021;12:816. ; Chen VL, Burkholder DA, Moran IJ, DiBattista JV, Miller MJ, Chen Y, et al. Hepatic decompensation is accelerated in patients with cirrhosis and alpha-1 antitrypsin Pi *MZ genotype. JHEP Rep. 2022;4:100483. ; Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509. ; Fan R, Papatheodoridis G, Sun J, Innes H, Toyoda H, Xie Q, et al. aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis. J Hepatol. 2020;73:1368–78. ; Johnson PJ, Innes H, Hughes DM, Kalyuzhnyy A, Kumada T, Toyoda H. Evaluation of the aMAP score for hepatocellular carcinoma surveillance: a realistic opportunity to risk stratify. Br J Cancer. 2022;127:1263–9. ; Emdin CA, Haas M, Ajmera V, Simon TG, Homburger J, Neben C, et al. Association of genetic variation with cirrhosis: A multi-trait genome-wide association and gene-environment interaction study. Gastroenterology. 2021;160:1620–33 e1613. ; Singal AG, Manjunath H, Yopp AC, Beg MS, Marrero JA, Gopal P, et al. The effect of PNPLA3 on fibrosis progression and development of hepatocellular carcinoma: A meta-analysis. Am J Gastroenterol. 2014;109:325–34. ; Valenti L, Aghemo A, Stattermayer AF, Maggioni P, De Nicola S, Motta BM, et al. Implications of PNPLA3 polymorphism in chronic hepatitis C patients receiving peginterferon plus ribavirin. Aliment Pharmacol Ther. 2012;35:1434–42. ; Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68:723–50. ; European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018;69:182–236. ; Atiq O, Tiro J, Yopp AC, Muffler A, Marrero JA, Parikh ND, et al. An assessment of benefits and harms of hepatocellular carcinoma surveillance in patients with cirrhosis. Hepatology. 2017;65:1196–205. ; Singal AG, Tiro JA, Murphy CC, Blackwell JM, Kramer JR, Khan A, et al. Patient-reported barriers are associated with receipt of hepatocellular carcinoma surveillance in a multicenter cohort of patients with cirrhosis. Clin Gastroenterol Hepatol. 2021;19:987–95 e981. ; Santi V, Trevisani F, Gramenzi A, Grignaschi A, Mirici-Cappa F, Del Poggio P, et al. Semiannual surveillance is superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival. J Hepatol. 2010;53:291–7. ; Trinchet JC, Chaffaut C, Bourcier V, Degos F, Henrion J, Fontaine H, et al. Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: A randomized trial comparing 3- and 6-month periodicities. Hepatology. 2011;54:1987–97. ; Pelizzaro F, Peserico G, D’Elia M, Cazzagon N, Russo FP, Vitale A, et al. Surveillance for hepatocellular carcinoma with a 3-months interval in “extremely high-risk” patients does not further improve survival. Dig Liver Dis. 2022;54:927–36. ; Park HJ, Kim SY, Singal AG, Lee SJ, Won HJ, Byun JH, et al. Abbreviated magnetic resonance imaging vs ultrasound for surveillance of hepatocellular carcinoma in high-risk patients. Liver Int. 2022;42:2080–92. ; Chen VL, Singal AG, Tapper EB, Parikh ND. Hepatocellular carcinoma surveillance, early detection and survival in a privately insured US cohort. Liver Int. 2020;40:947–55. ; Bruschi FV, Claudel T, Tardelli M, Caligiuri A, Stulnig TM, Marra F, et al. The PNPLA3 I148M variant modulates the fibrogenic phenotype of human hepatic stellate cells. Hepatology. 2017;65:1875–90. ; Liu YL, Patman GL, Leathart JB, Piguet AC, Burt AD, Dufour JF, et al. Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol. 2014;61:75–81. ; Mandorfer M, Scheiner B, Stattermayer AF, Schwabl P, Paternostro R, Bauer D, et al. Impact of patatin-like phospholipase domain containing 3 rs738409 G/G genotype on hepatic decompensation and mortality in patients with portal hypertension. Aliment Pharmacol Ther. 2018;48:451–9.
  • Grant Information: K08 DK132312 United States DK NIDDK NIH HHS
  • Substance Nomenclature: EC 3.1.1.3 (PNPLA3 protein, human) ; EC 3.1.1.3 (Lipase) ; 0 (Membrane Proteins) ; EC 1.1.-.- (HSD17B13 protein, human) ; EC 1.1.- (17-Hydroxysteroid Dehydrogenases) ; 0 (TM6SF2 protein, human) ; EC 2.3.- (Acyltransferases) ; EC 3.1.1.4 (Phospholipases A2, Calcium-Independent)
  • Entry Date(s): Date Created: 20240523 Date Completed: 20240523 Latest Revision: 20240607
  • Update Code: 20240608
  • PubMed Central ID: PMC11124711

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