lancet-header
Preprints with The Lancet is part of SSRN´s First Look, a place where journals and other research experts identify content of interest prior to publication. These preprint papers are not peer-reviewed and are posted here as part of a 12-month trial. Authors have either opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet, or submitted directly via SSRN. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. These papers should not be used for clinical decision making or reporting of research to a lay audience without indicating that this is preliminary research that has not been peer-reviewed. For more information see the Comment published in The Lancet, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com

PNPLA3 Rs738409 C>G Variant Predicts Liver-Related Outcomes in Patients with Non-Alcoholic Fatty Liver Disease

38 Pages Posted: 8 Mar 2019

See all articles by Stefania Grimaudo

Stefania Grimaudo

University of Palermo - Biomedical Department of Internal and Specialized Medicine (DI.BI.M.I.S.)

Rosaria Maria Pipitone

University of Palermo - Biomedical Department of Internal and Specialized Medicine (DI.BI.M.I.S.)

Grazia Pennisi

University of Palermo

Ciro Celsa

University of Palermo

Calogero Cammà

University of Palermo

Vito Di Marco

University of Palermo - Biomedical Department of Internal and Specialized Medicine (DI.BI.M.I.S.)

Roberta Boemi

University of Palermo

Aurora Giannetti

University of Palermo

Federica Spatola

University of Palermo

Giulio Marchesini

Università "Alma Mater"

Antonio Craxì

University of Palermo

Salvatore Petta

University of Palermo

More...

Abstract

Background: Patients with NAFLD are at higher risk of developing liver-related complications -liver decompensation(LD) and hepatocellular carcinoma (HCC), including death-. A single nucleotide polymorphism in PNPLA3 gene is associated with a higher prevalence of liver damage and HCC, but prospective date are not available. We aimed to assess whether the common rs738409 variant in PNPLA3 gene can predict the occurrence of liver-related events and death in a large cohort of NAFLD patients.  

Methods: We considered 471 consecutive Italian individuals with histological diagnosis of NAFLD or clinical diagnosis of compensated NAFLD-related cirrhosis, prospectively followed for at least 6 months. The occurrence of hepatic and extrahepatic outcomes was recorded (LD and HCC; cardiovascular events and extrahepatic cancers, overall and liver-related death). The rs738409 G>C polymorphisms was genotyped by TaqMan assay.  

Findings: During a median follow-up of 64.6 months  26 LD, 13 HCC and 16 deaths (12 liver-related) were recorded. All liver-related events including liver-related death, occurred in patients with F3 fibrosis or cirrhosis. After adjusting for clinico-metabolic and histological risk factors PNPLA3 C>G variant was associated with a higher risk of LD(HR 2.10,95%C.I.1.03-4.29, p=0.04), HCC (HR 2.68,95%C.I.1.01-7.26, p=0.04) and liver-related death (HR 3.64, 5%C.I.1.18-11.2, p=0.02) by multivariate Cox regression analysis. In the subgroup of 162 patients with F3 fibrosis or cirrhosis we confirmed the independent association of PNPLA3 variant with LD (HR 2.00,95%C.I.1.01-3.97, p=0.04), HCC (HR 2.66,95%C.I.1.02-7.13, p=0.04) and liver-related death (HR 3.64,95%C.I.1.18-11.2, p=0.02). No association was found between PNPLA3 genotype and cardiovascular events, extrahepatic cancers and overall mortality.  

Interpretations: Patients carrying PNPLA3 rs738409 G>C variant are at higher risk of developing liver-related events and death.  

Funding: None.  

Declaration of Interest: None.

Ethical Approval: The study was carried out in accordance with the principles of the Helsinki Declaration, and with local and national laws. Approval was obtained from the AOUP “Giaccone” of Palermo.

Keywords: NAFLD, NASH, PNPLA3, Cirrhosis, Decompensation, HCC, Death

Suggested Citation

Grimaudo, Stefania and Pipitone, Rosaria Maria and Pennisi, Grazia and Celsa, Ciro and Cammà, Calogero and Di Marco, Vito and Boemi, Roberta and Giannetti, Aurora and Spatola, Federica and Marchesini, Giulio and Craxì, Antonio and Petta, Salvatore, PNPLA3 Rs738409 C>G Variant Predicts Liver-Related Outcomes in Patients with Non-Alcoholic Fatty Liver Disease (March 6, 2019). Available at SSRN: https://ssrn.com/abstract=3347913

Stefania Grimaudo

University of Palermo - Biomedical Department of Internal and Specialized Medicine (DI.BI.M.I.S.)

Palermo
Italy

Rosaria Maria Pipitone

University of Palermo - Biomedical Department of Internal and Specialized Medicine (DI.BI.M.I.S.)

Palermo
Italy

Grazia Pennisi

University of Palermo

Viale delle Scienza
Palermo, 90128
Italy

Ciro Celsa

University of Palermo

Viale delle Scienza
Palermo, 90128
Italy

Calogero Cammà

University of Palermo ( email )

Viale delle Scienza
Palermo, 90128
Italy

Vito Di Marco

University of Palermo - Biomedical Department of Internal and Specialized Medicine (DI.BI.M.I.S.)

Palermo
Italy

Roberta Boemi

University of Palermo

Viale delle Scienza
Palermo, 90128
Italy

Aurora Giannetti

University of Palermo

Viale delle Scienza
Palermo, 90128
Italy

Federica Spatola

University of Palermo

Viale delle Scienza
Palermo, 90128
Italy

Giulio Marchesini

Università "Alma Mater"

Bologna
Italy

Antonio Craxì

University of Palermo ( email )

Viale delle Scienza
Palermo, 90128
Italy

Salvatore Petta (Contact Author)

University of Palermo

Viale delle Scienza
Palermo, 90128
Italy

Click here to go to TheLancet.com

Go to TheLancet.com

Paper statistics

Abstract Views
98
Downloads
16