Influence of Genetic Variants on Disease Regression and Outcomes in HCV-Related Advanced Chronic Liver Disease after SVR

Author:

Semmler GeorgORCID,Binter Teresa,Kozbial Karin,Schwabl PhilippORCID,Chromy DavidORCID,Bauer DavidORCID,Simbrunner Benedikt,Müllner-Bucsics Theresa,Scheiner BernhardORCID,Stättermayer AlbertORCID,Pinter MatthiasORCID,Steindl-Munda Petra,Trauner MichaelORCID,Ferenci PeterORCID,Reiberger ThomasORCID,Mandorfer Mattias

Abstract

Genetic variants including PNPLA3-rs738409 C>G, TM6SF2-rs58542926 C>T, MBOAT7-rs641738 C>T, and HSD17B13-rs72613567 T>TA have been shown to influence progression to advanced chronic liver disease (ACLD) in patients with chronic hepatitis C (CHC). We aimed to investigate their impact on disease regression (i.e., changes in hepatic venous pressure gradient [HVPG] and non-invasive surrogates [liver stiffness measurement (LSM), von Willebrand factor (VWF), and VWF/platelet count ratio (VITRO)]) and clinical outcomes after CHC cure in 346 patients with pre-treatment ACLD. Patients carrying the PNPLA3 minor allele had more advanced liver disease prior to antiviral therapy, confirming its impact on liver disease progression. In a subgroup of 88 patients who underwent paired HVPG-measurements and were genotyped for all SNP/indels, PNPLA3/TM6SF2/MBOAT7/HSD17B13 genotypes were not associated with changes in HVPG. In line, changes in non-invasive surrogates of portal hypertension (LSM/VWF/VITRO) were comparable between carriers and non-carriers of the PNPLA3 G-allele in the overall cohort. Finally, carriage of PNPLA3 G-allele was not associated with the development of hepatic decompensation, de-novo hepatocellular carcinoma, or transplant-free mortality during a median follow-up of 42 months after the end of antiviral treatment. Therefore, genetic variants in PNPLA3/TM6SF2/MBOAT7/HSD17B13 do not impact the regression of portal hypertension and clinical outcomes in patients with pre-treatment ACLD after CHC cure.

Funder

Medical Scientific Fund of the Major of the City of Vienna

European Association for the Study of the Liver

Publisher

MDPI AG

Subject

Medicine (miscellaneous)

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