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

BMI increase is commonly described in patients after chronic hepatitis C (HCV) cure with direct-acting antivirals. The aims of our study were to confirm the BMI increase compared with a population control group and to search for the allelic association between BMI increase and PNPLA3 gene I148M variant (G allele) carriage. We compared the BMI increase in 230 patients (HCV group) 3 years after the end of anti-HCV treatment with a group of 640 healthy subjects (controls) within the same period. The median BMI increase in the HCV group was 0.39 (range - 6.5-11.8), 0.70 in controls (-6.3 - 14.0); the difference was not significant (p = 0.95). However, the HCV subgroups showed significant difference according to PNPLA3 genotype: CC 0.0 (-6.5-8.7) vs. CG + GG 0.94 (-4.2-11.8), p = 0.0045, in contrast to the subgroups of controls: CC 0.7 (-5.1-13.7) vs. CG + GG 0.7 (-0.3-14.90), p = 0.86. BMI increase in the HCV subgroup CC + CG was significantly higher than in the entire control group (p = 0.035), whereas the HCV subgroup CC did not differ from controls (p = 0.07). The BMI increase was associated with PNPLA3 G allele carriage in the allelic model and the multivariate analysis.