GWA studies reported that the rs4374383 SNP of MERTK gene is associated with the risk of developing fibro-sis in patients with HCV chronic hepatitis. We evaluated if rs4374383 SNP influenced the risk of liver decompensation (LD) and hepatocellular carcinoma (HCC) in patients with HCV cirrhosis undergoing antiviral therapy. Methods: In a prospective cohort of patients with compensated HCV cirrhosis treated with Peg-interferon Pexidartinib clinical trial alfa-2b and ribavirin (P/R), rs4374383 SNP was carried out using the TaqMan SNP genotyping allelic discrimination method (Applied Biosystems, CA, USA) on sera stored before treatment. All patients were screened for esophageal varices (EV) before

treatment and underwent surveillance for HCC every six months. Univariate and multivariate Cox regression analysis was used to determine factors associated with development of LD and HCC. Results: Among 349 patients (mean age 58±8.6 years, 61.2% men, 85% genotype 1) included in this analysis, 16.9% had AA genotype, 46.4% GA genotype and 36.9% GG genotype selleck chemicals of rs4374383 SNP, and 50.7% had EV at baseline. Eighty-seven patients (24.9%) achieved a Sustained Virological Response (SVR). During follow-up (median 77 months; range 12-145) 6 (6.8%) SVR and in 71 (27.1%) no SVR patients developed LD (p<0.001), while 6 patients (6.8%) with SVR and 66 patients (25.2%) without SVR developed HCC (p<0.001). By multivariate analysis EV (HR 3.11; 95%CI 1.69-5.75; p<0.001),

platelet count (HR 0.99; 95%CI 0.98-0.99; p=0.001), albumin (HR: 3.11; 95%CI 0.19-0.54; p<0.001), and absence of SVR (HR: 4.04; 95%CI 1.63 -10.05; p= 0.003) were independently associated to LD. The variables independently associated to development of HCC were age (HR 1.04; 95%CI 1.01-1.07; p=0.045), GGT (HR 1.14; 95%CI 1.20-1.37, p=0.008), absence of SVR (HR 3.31; 95%CI 1.43-7.68; p=0.005) and the AA genotype of rs4374383 SNP (HR 2.67; 95% CI 1.36 -5.23; p= 0.004). The risk of developing HCC was of 1.04 per 100 persons/years in patients with SVR, and of 2.43, 4.05 and 7.17 per 100 persons/years aminophylline in non responders to therapy with genotype GG, GA and AA of rs4374383

SNP, respectively. Conclusion: The AA allele of rs4374383 SNP of MERTK gene is associated with a higher risk of developing HCC in patients with HCV cirrhosis not responding to P/R. Since the MERTK gene is a regulator of tumor-associated macrophages involved in the modulation of inflammatory responses and in angiogenesis, its polymorphism could affect the rate of development of HCC in a predisposed population. Disclosures: The following people have nothing to disclose: Vito Di Marco, Vincenza Cal-varuso, Stefania Grimaudo, Donatella Ferraro, Maria Grazia Bavetta, Antonietta Di Cristina, Giuseppe Cabibbo, Elisabetta Conte, Antonio Craxi Background&Aims: Genetic variation in IL28B has been found as a predictive factor for pegylated-interferon/ribavirin (Peg-IFN/RBV) therapy in chronic hepatitis C (CHC) patients.