The PNPLA3 G-allele is common in patients with HCC but does not affect tumor characteristics and tumor biology

Background and Aims The G-allele of the of patatin-like phospholipase domain-containing protein 3 (PNPLA3) is an established risk factor for hepatic lipid accumulation and the development of advanced liver disease and HCC. This study explores a possible link between the PNPLA3 G-allele and HCC tumor characteristics and biology.

Method Patients referred for PNPLA3 genotyping to the Hepatology Laboratory at the Medical University of Innsbruck were retrospectively assessed and included if the diagnosis HCC was made with multiphasic CT and/or dynamic contrast-enhanced MRI (n = 197). Tumor characteristics were assessed independently by two radiologists. An unselected PNPLA3 genotyped cohort of cirrhotic patients without HCC (n = 1489) was used as a control group. Demographic, clinical and biochemical parameters were extracted from patient records.

Results Of 197 (31 women) unselected HCC patients the G-allele prevalence was 70.6 % (46.2 % homozygous and 24.4 % heterozygous). The allele frequency was not significantly different in an unselected cohort of cirrhotic patients (64.6 %, p = 0.137) but far more frequent as in the general European population (allele frequency 0.228). At baseline (time of genotyping) age, median MELD scores and BMI did not differ between groups. When patients were grouped according to PNPLA3 genotype no significant difference was observed in BCLC tumor stage, mRECIST defined tumor progression, tumor diameter and number, vascular tumor invasion and occurrence of extrahepatic metastasis. No association between PNPLA3 and the combined endpoint death/liver transplantation was found. All before mentioned endpoints did also not differ between heterozygous and homozygous carriers.

Conclusion Although G allele carriers in rs738409 of PNPLA3 are known to be at increased risk of developing advanced fibrosis and HCC, no association between PNPLA3 genotype and tumor characteristics, tumor biology or treatment response were found.

Publication History

Article published online:
26 May 2020