O-1 THE ROLE OF PNPLA3 AND TM6SF2 POLYMORPHISMS ON LIVER FIBROSIS AND METABOLIC ABNORMALITIES IN BRAZILIAN PATIENTS WITH CHRONIC HEPATITIS C

Abstract

Background: Despite the growing body of knowledge about TM6SF2 and PNPLA3 polymorphisms in non-alcoholic fatty liver disease, their influence in the spectrum of HCV liver disease is not yet fully defined. Besides that, admixed populations, such as Brazilians, were not included in most of the studies. Objectives: Describe the prevalence of these polymorphisms in Brazilians with chronic hepatitis C, and to assess their association with liver fibrosis and other components of the metabolic syndrome. Methods: This cross-sectional study enrolled 365 treatment-naïve patients with HCV and 134 healthy individuals. TM6SF2 (rs58542926 c.499C>T) and PNPLA3 (rs738409 c.444C>G) polymorphisms were evaluated regarding their association with clinical and laboratory data, histological liver steatosis and fibrosis, and with components of the metabolic syndrome. Results: In HCV subjects, the frequencies of TM6SF2 CC and CT + TT were 89% and 11%, while PNPLA3 frequencies of CC and CG + GG were 51.4% and 48.6%. In the univariate logistic regression analysis, the TM6SF2 CT + TT genotype in HCV was associated with significant liver fibrosis (p = 0.047; OR:1.953; 95% CI:1.009-3.788) however it was not confirmed by multivariate analysis. In comparison to the CT + TT genotype, the TM6SF2 CC genotype in HCV was associated higher frequency of arterial hypertension (p = 0.032), obesity (p = 0.030), metabolic syndrome (p = 0.014) and lower total cholesterol levels (p=0.036). The PNPLA3 GG subjects had lower body mass index than CG/ CC individuals (p = 0.047). None of the polymorphisms, or their combinations, was independently associated with hepatic steatosis. Conclusion: In this evaluation of an admixed HCV population, neither TM6SF2 nor PNPLA3 polymorphisms were independently associated with hepatic steatosis or fibrosis.