Role of TLL1 Gene Polymorphism in Development of Hepatocellular Carcinoma in Egyptian Cirrhotic Patients Achieving Sustained Virological Response by Direct Acting Antiviral Agents for HCV

Abstract

Background and aim: Host genetic factors have been recognized as potential determinants of denovo occurrence of hepatocellular carcinoma (HCC) in patients with HCV related cirrhosis even after achieving sustained virological response (SVR) with direct antiviral agents (DAAs). We investigated whether rs17047200 in TLL1 gene is associated with early development of HCC in Hepatitis C Virus (HCV) cirrhotic Egyptian patients treated after eradication with antivirals (DAAs)

Materials and Methods: 50 patients with SVR developed denovo HCC (HCC group) within 6 months after end of treatment were included and compared to 50 patients who achieved SVR without HCC development (non HCC group). TLL1 rs17047200 polymorphism was analyzed in both groups.

Results: In HCC group rs17047200 in TLL1 gene was AA in 34 (68.0%), AT in 9 (18%), TT in 2 (4%) and undetermined in 5 patients (10%). In non HCC group, AA genotype was in 25 (50.0%), AT in 16 (32 %), TT in 2 (4%) and undetermined in 7(14%), with no significant difference between 2 groups. There was no significant association between TLL1 gene variants and HCC features or baseline clinical and investigational characteristics in HCC group. Multivariate analyses identified age >50, male sex, baseline higher liver stiffness and higher baseline FIB-4 score as independent predictors of  HCC occurrence  in patients achieving SVR within 6 months after DAAs for HCV infection.

Conclusion: TLL1 genotypes do not predict HCC development after HCV eradication by DAAs.