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PNPLA3 I148M variant is the main driver of weight gain after hepatitis C cure

V Pitova1,2, S Frankova1, M Holinka1,3

  • 1Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Scientific Reports
|July 15, 2025
PubMed

Insights

Patients cured of chronic hepatitis C (HCV) with direct-acting antivirals showed increased BMI, particularly those with the PNPLA3 G allele. This genetic factor influences BMI changes post-HCV treatment.

Area of Science:

  • Hepatology
  • Genetics
  • Metabolic Health

Background:

  • Direct-acting antivirals (DAAs) effectively cure chronic hepatitis C (HCV).
  • Increased body mass index (BMI) is frequently observed after HCV cure.
  • The PNPLA3 gene I148M variant (G allele) is linked to liver fat accumulation.

Purpose of the Study:

  • To confirm BMI increase in patients post-HCV cure compared to controls.
  • To investigate the association between BMI increase and PNPLA3 G allele carriage.

Main Methods:

  • Compared BMI changes in 230 HCV patients 3 years post-DAA treatment with 640 healthy controls.
  • Analyzed BMI changes based on PNPLA3 genotypes (CC vs. CG+GG).
  • Utilized allelic and multivariate models for association analysis.

Main Results:

  • Overall BMI increase was not significantly different between HCV patients and controls.
  • HCV patients with PNPLA3 CG+GG genotypes showed a significantly higher BMI increase than CC genotype (p=0.0045).
  • BMI increase was significantly associated with PNPLA3 G allele carriage in HCV patients.

Conclusions:

  • BMI increase after HCV cure is influenced by PNPLA3 genotype.
  • PNPLA3 G allele carriage is a significant predictor of BMI increase post-HCV treatment.
  • Genetic factors play a role in metabolic changes following successful HCV therapy.
Keywords:
PNPLA3Direct-acting antiviralsHepatitis C virusWeight gain

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