TLL1 variants do not predict hepatocellular carcinoma development in HCV cirrhotic patients treated with direct‐acting antivirals

摘要

Abstract Tolloid‐like 1 gene (TLL1) variant rs17047200 has been associated with hepatocellular carcinoma (HCC) in Japanese hepatitis C virus (HCV) patients with sustained virological response (SVR) to interferon or direct‐acting antiviral (DAA)‐based regimens. We investigated whether this holds true also in Caucasian cirrhotic patients cured by DAAs. Consecutive Caucasian HCV cirrhotics receiving DAA between December 2014 and December 2016 in a single centre were enrolled. Cirrhosis was defined histologically (METAVIR F4) or by liver stiffness measurement (LSM??11.9?kPa). TLL1 rs17047200 was analysed by TaqMan SNP genotyping assay. 452 patients were enrolled: median age 63 (28‐87)?years, 58% males, 47% HCV‐1b, LSM 19.1 (12.0‐75.0)?kPa and Fibrosis‐4 (FIB‐4) score 4.9 (0.3‐46.0). 96% patients achieved an SVR. TLL1 genotype was AA in 329 (73%) and AT/TT in 123 (27%) (MAF?=?0.14, HWE P ??0.05). Patients’ clinical features were similar across TLL1 genotypes. After 33 (3‐47)?months from DAA start, 31 patients developed HCC, with a 3‐year estimated cumulative probability being 7.5% (95% CI: 5%‐10%). The cumulative incidence of HCC was 9% in TLL1 AA vs 7% in AT/TT patients ( P ?=?0.55). Male sex (HR: 3.78, 95% CI: 1.4‐10.1, P ?=?0.008), diabetes (HR: 3.5, 95% CI: 1.68‐7.27, P ?=?0.001) and FIB‐4 (HR: 1.09, 95% CI: 1.03‐1.14, P ?=?0.001) were baseline‐independent predictors of HCC. The incidence of HCC was not influenced by TLL1 genotypes even when considering an additional group of 348 noncirrhotic patients, being 2% in AA vs 1% AT/TT patients ( P ?=?0.58). In a large cohort of Caucasian HCV cirrhotics treated with DAA, TLL1 variants do not predict HCC development.