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

Elisabetta Degasperi, Enrico Galmozzi, Floriana Facchetti, Elisa Farina, Roberta D'Ambrosio, Roberta Soffredini, Massimo Iavarone, Pietro Lampertico

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1233-1236
JournalJournal of Viral Hepatitis
Volume26
Issue number10
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Hepacivirus
Antiviral Agents
Hepatocellular Carcinoma
Genes
Fibrosis
Genotype
Incidence
Interferons
Single Nucleotide Polymorphism
Liver

Keywords

  • cirrhosis
  • direct-acting antiviral
  • hepatitis C virus
  • hepatocellular carcinoma
  • rs17047200
  • tolloid-like 1 gene

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases
  • Virology

Cite this

@article{e2e19c05f8ad49b991da9260a0877aaf,
title = "TLL1 variants do not predict hepatocellular carcinoma development in HCV cirrhotic patients treated with direct-acting antivirals",
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.",
keywords = "cirrhosis, direct-acting antiviral, hepatitis C virus, hepatocellular carcinoma, rs17047200, tolloid-like 1 gene",
author = "Elisabetta Degasperi and Enrico Galmozzi and Floriana Facchetti and Elisa Farina and Roberta D'Ambrosio and Roberta Soffredini and Massimo Iavarone and Pietro Lampertico",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/jvh.13155",
language = "English",
volume = "26",
pages = "1233--1236",
journal = "Journal of Viral Hepatitis",
issn = "1352-0504",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "10",

}

TY - JOUR

T1 - TLL1 variants do not predict hepatocellular carcinoma development in HCV cirrhotic patients treated with direct-acting antivirals

AU - Degasperi, Elisabetta

AU - Galmozzi, Enrico

AU - Facchetti, Floriana

AU - Farina, Elisa

AU - D'Ambrosio, Roberta

AU - Soffredini, Roberta

AU - Iavarone, Massimo

AU - Lampertico, Pietro

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - cirrhosis

KW - direct-acting antiviral

KW - hepatitis C virus

KW - hepatocellular carcinoma

KW - rs17047200

KW - tolloid-like 1 gene

UR - http://www.scopus.com/inward/record.url?scp=85068207121&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068207121&partnerID=8YFLogxK

U2 - 10.1111/jvh.13155

DO - 10.1111/jvh.13155

M3 - Article

C2 - 31177595

AN - SCOPUS:85068207121

VL - 26

SP - 1233

EP - 1236

JO - Journal of Viral Hepatitis

JF - Journal of Viral Hepatitis

SN - 1352-0504

IS - 10

ER -