Impact of genetic variants on regression of portal hypertension and clinical outcomes in ACLD patients after SVR

Objectives Single nucleotide polymorphisms (SNPs) including PNPLA3 rs738409 C > G, TM6SF2 rs58542926 C > T, MBOAT7 rs641738 C > T, and HSD17B13 rs72613567 T > TA impact on progression to advanced chronic liver disease(ACLD) in patients with hepatitis C virus (HCV) infection. However, their impact on disease regression after HCV cure remains unclear.

Methods We investigated the impact of genetic variants in PNPLA3, TM6SF2, MBOAT7, and HSD17B13 on the regression of portal hypertension, as assessed by (I) changes in hepatic venous pressure gradient(HVPG), (II) non-invasive surrogates such as liver stiffness measurement (LSM), von Willebrand factor (VWF), and the VWF/platelet count ratio (VITRO), and (III) clinical events in 339 HCV patients with pre-treatment ACLD who achieved sustained virologic response (SVR) to interferon-free therapies.

Results Patients harboring a PNPLA3 risk allele had more advanced liver disease at baseline, confirming its impact on liver disease progression.In a subgroup of 88 patients undergoing paired HVPG measurements the PNPLA3/TM6SF2/MBOAT7/HSD17B13 genotypes were not associated with changes in HVPG. In line, changes of LSM, VWF and VITRO as non-invasive surrogates of portal hypertension were comparable between carriers and non-carriers of the PNPLA3 rs738409 G-allele in the overall cohort.Finally, carriage of PNPLA3 rs738409 G-allele was not associated an increased risk for development of hepatic decompensation or hepatocellular carcinoma, nor with liver-related mortality during a median follow-up of 38 months after SVR.

Conclusions Genetic variants in PNPLA3/TM6SF2/MBOAT7/HSD17B13 do not impact on the regression of portal hypertension and clinical outcomes after HCV cure in patients with pre-treatment ACLD.

Publication History

Article published online:
26 May 2020