# The impact of the PNPLA3 rs738406 C>G polymorphism on hepatocellular carcinoma risk in Brazilian patients with chronic hepatitis C and advanced fibrosis

## TL;DR

This study found no link between a specific genetic variant and liver cancer risk in Brazilian patients with chronic hepatitis C and advanced liver damage.

## Contribution

This is the first study to evaluate the association of the PNPLA3 rs738409 polymorphism with HCC risk in the Brazilian population.

## Key findings

- The PNPLA3 rs738409 polymorphism was not associated with HCC risk in Brazilian CHC patients with advanced fibrosis.
- Gender, tobacco consumption, and ALBI score were independent factors associated with HCC development.
- No significant differences in PNPLA3 genotype frequencies were observed between HCC and non-HCC groups.

## Abstract

•PNPLA3 rs738409 polymorphism was associated with fibrosis and steatosis in CHC patients.•The impact on HCC risk is not yet well defined.•This was the first evaluation of this association in the Brazilian population.•PNPLA3 rs738409 polymorphism was not associated with HCC risk in the studied population.

PNPLA3 rs738409 polymorphism was associated with fibrosis and steatosis in CHC patients.

The impact on HCC risk is not yet well defined.

This was the first evaluation of this association in the Brazilian population.

PNPLA3 rs738409 polymorphism was not associated with HCC risk in the studied population.

The PNPLA3 rs738409 C>G polymorphism has been associated with fibrosis and steatosis in Chronic Hepatitis C (CHC) patients. However, its impact on Hepatocellular Carcinoma (HCC) development in this population remains unclear. This study aimed to evaluate the impact of the PNPLA3 polymorphism on the risk of HCC development in CHC patients in Brazil.

This retrospective case-control study included 235 CHC patients with advanced fibrosis, 119 with HCC, and 116 without HCC. The PNPLA3 polymorphism was analyzed using both the dominant and recessive models. Multivariate logistic regression was performed to assess factors independently associated with HCC development.

The HCC group exhibited a higher proportion of male patients (p < 0.0001), alcohol abuse (p < 0.001), tobacco consumption (p < 0.0001), and ALBI grade 2‒3 (p < 0.001). The PNPLA3 genotype frequencies were CC 45.4%, CG 46.2% and GG 8.4% in the HCC group, and CC 51.7%, CG 40.5% and GG 7.8% in the non-HCC group. No significant differences in genotype frequencies were observed for the dominant model (p = 0.33) or the recessive model (p = 0.92). Gender (p = 0.001), tobacco consumption (p < 0.001), and ALBI score (p = 0.012) were identified as independent factors associated with HCC development. However, the PNPLA3 G allele was not an independent factor associated with HCC risk in either the univariate analysis (OR = 1.15, 95% CI 0.63‒2.08, p = 0.65) or the multivariate analysis (OR = 0.99, 95% CI 0.49‒2.00, p = 0.98).

The PNPLA3 rs738409 polymorphism was not associated with HCC development in CHC patients with advanced fibrosis in the Brazilian population. Further studies are required to confirm this finding.