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 antivirals (DAA)-based regimens. We investigated if this holds true also in Caucasian cirrhotic patients cured by DAAs. Consecutive Caucasian HCV cirrhotics receiving DAA between December 2014-2016 in a single Center were enrolled. Cirrhosis was defined histologically (METAVIR F4) or by liver stiffness measurement (LSM >11.9 kPa). TLL1 rs17047200 was analyzed 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, Fibrosis-4 (FIB-4) score 4.9 (0.3-46.0). 96% patients achieved an SVR. TLL1 genotype was AA in 329 (73%), 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, 3-year estimated cumulative probability being 7.5% (95% CI 5-10%). 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. Incidence of HCC was not influenced by TLL1 genotypes even when considering an additional group of 348 non-cirrhotic 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.

TLL1 Variants do not predict hepatocellular carcinoma development in hcv cirrhotic patients treated with direct-acting antivirals / E. Degasperi, E. Galmozzi, F. Facchetti, E. Farina, R. D'Ambrosio, R. Soffredini, M. Iavarone, P. Lampertico. - In: JOURNAL OF VIRAL HEPATITIS. - ISSN 1352-0504. - 26:10(2019 Oct 01), pp. 1233-1236. [10.1111/jvh.13155]

TLL1 Variants do not predict hepatocellular carcinoma development in hcv cirrhotic patients treated with direct-acting antivirals

E. Degasperi
Primo
;
E. Galmozzi
Secondo
;
E. Farina;P. Lampertico
Ultimo
2019-10-01

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 antivirals (DAA)-based regimens. We investigated if this holds true also in Caucasian cirrhotic patients cured by DAAs. Consecutive Caucasian HCV cirrhotics receiving DAA between December 2014-2016 in a single Center were enrolled. Cirrhosis was defined histologically (METAVIR F4) or by liver stiffness measurement (LSM >11.9 kPa). TLL1 rs17047200 was analyzed 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, Fibrosis-4 (FIB-4) score 4.9 (0.3-46.0). 96% patients achieved an SVR. TLL1 genotype was AA in 329 (73%), 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, 3-year estimated cumulative probability being 7.5% (95% CI 5-10%). 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. Incidence of HCC was not influenced by TLL1 genotypes even when considering an additional group of 348 non-cirrhotic 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.
DAA ; HCC ; HCV ; TLL1; cirrhosis; rs17047200
Settore MED/12 - Gastroenterologia
8-giu-2019
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/650306
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