Factors Associated With Increased Risk of De Novo or Recurrent Hepatocellular Carcinoma in Patients With Cirrhosis Treated With Direct-Acting Antivirals for HCV Infection

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Abstract

Background & Aims: Patients with cirrhosis and hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs) are still at risk for developing hepatocellular carcinoma (HCC). We aimed to identify features of de novo or recurrent HCCs in these patients, and factors associated with HCC development, in a large cohort of patients with cirrhosis who received treatment with DAAs. Methods: In a retrospective study, we collected data from 565 patients with cirrhosis (median age, 64 years; range, 28–87 years; 60% male, 49% infected with HCV genotype 1; median liver stiffness measurement [LSM], 19.1 kPa; 87% Child-Pugh-Turcotte score A) treated with DAAs at a single center in Italy, from December 2014 through 2016. Cirrhosis was defined based on clinical features, histologic factors (METAVIR F4), or LSM >11.9 kPa. Patients were assessed (complete blood analysis and HCV-RNA quantification) every 4 weeks during treatment; at weeks 4, 12, and 24 afterward; and at 6-month intervals thereafter. HCC surveillance was performed by ultrasound or CT scans every 3–6 months, based on history of HCC. Non-invasive markers of fibrosis, such as ratio of aspartate aminotransferase to platelets, fibrosis-4 (FIB-4) score, and LSMs were assessed. Results: During a median 25 months of follow up (range, 3–39 months), HCC developed in 28/505 patients without a history of HCC (de novo HCC); the 3-year estimated cumulative probability for HCC was 6% (95% CI, 4%–9%). Of patients with de novo HCC, 75% had a single tumor and 82% of these were Barcelona liver cancer stage 0–A; the median level of alpha-fetoprotein was 6 ng/mL (range, 1.0–9240 ng/mL). Male sex (hazard ratio [HR], 6.17; 95% CI, 1.44–26.47; P =.01), diabetes (HR, 2.52; 95% CI, 1.08–5.87; P =.03), LSM (HR, 1.03; 95% CI, 1.01–1.06; P =.01), and FIB-4 score (HR, 1.08; 95% CI, 1.01–1.14; P =.01) were independently associated with de novo HCC. HCC developed in 20/60 patients with a history of HCC (HCC recurrence); the 3-year cumulative probability for recurrence was 43% (95% CI, 20%–61%). In the 20 patients with HCC recurrence, 11 had a single tumor and 90% were Child-Pugh-Turcotte score A. Diabetes was independently associated with HCC recurrence (HR, 4.12; 95% CI, 1.55–10.93; P =.004). Conclusions: In a large, single-center cohort of consecutive patients with cirrhosis and who received DAA treatment for HCV infection, most liver tumors were identified at early stages. Male sex, diabetes, and non-invasive markers of liver fibrosis can be used to identify patients at increased risk for HCC following DAAs therapy.

Original languageEnglish
Pages (from-to)1183-1191.e7
JournalClinical Gastroenterology and Hepatology
Volume17
Issue number6
DOIs
Publication statusPublished - May 1 2019

Fingerprint

Virus Diseases
Hepacivirus
Antiviral Agents
Hepatocellular Carcinoma
Fibrosis
Recurrence
Liver
Neoplasms
Sex Ratio
alpha-Fetoproteins
Therapeutics
Liver Neoplasms
Aspartate Aminotransferases
Liver Cirrhosis
Italy

Keywords

  • Direct-Acting Antivirals
  • HCV
  • Hepatocellular Carcinoma
  • IFN-Free Regimens
  • Predictors

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

@article{fa61d6a4d7444a62a62787f5a53d26ab,
title = "Factors Associated With Increased Risk of De Novo or Recurrent Hepatocellular Carcinoma in Patients With Cirrhosis Treated With Direct-Acting Antivirals for HCV Infection",
abstract = "Background & Aims: Patients with cirrhosis and hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs) are still at risk for developing hepatocellular carcinoma (HCC). We aimed to identify features of de novo or recurrent HCCs in these patients, and factors associated with HCC development, in a large cohort of patients with cirrhosis who received treatment with DAAs. Methods: In a retrospective study, we collected data from 565 patients with cirrhosis (median age, 64 years; range, 28–87 years; 60{\%} male, 49{\%} infected with HCV genotype 1; median liver stiffness measurement [LSM], 19.1 kPa; 87{\%} Child-Pugh-Turcotte score A) treated with DAAs at a single center in Italy, from December 2014 through 2016. Cirrhosis was defined based on clinical features, histologic factors (METAVIR F4), or LSM >11.9 kPa. Patients were assessed (complete blood analysis and HCV-RNA quantification) every 4 weeks during treatment; at weeks 4, 12, and 24 afterward; and at 6-month intervals thereafter. HCC surveillance was performed by ultrasound or CT scans every 3–6 months, based on history of HCC. Non-invasive markers of fibrosis, such as ratio of aspartate aminotransferase to platelets, fibrosis-4 (FIB-4) score, and LSMs were assessed. Results: During a median 25 months of follow up (range, 3–39 months), HCC developed in 28/505 patients without a history of HCC (de novo HCC); the 3-year estimated cumulative probability for HCC was 6{\%} (95{\%} CI, 4{\%}–9{\%}). Of patients with de novo HCC, 75{\%} had a single tumor and 82{\%} of these were Barcelona liver cancer stage 0–A; the median level of alpha-fetoprotein was 6 ng/mL (range, 1.0–9240 ng/mL). Male sex (hazard ratio [HR], 6.17; 95{\%} CI, 1.44–26.47; P =.01), diabetes (HR, 2.52; 95{\%} CI, 1.08–5.87; P =.03), LSM (HR, 1.03; 95{\%} CI, 1.01–1.06; P =.01), and FIB-4 score (HR, 1.08; 95{\%} CI, 1.01–1.14; P =.01) were independently associated with de novo HCC. HCC developed in 20/60 patients with a history of HCC (HCC recurrence); the 3-year cumulative probability for recurrence was 43{\%} (95{\%} CI, 20{\%}–61{\%}). In the 20 patients with HCC recurrence, 11 had a single tumor and 90{\%} were Child-Pugh-Turcotte score A. Diabetes was independently associated with HCC recurrence (HR, 4.12; 95{\%} CI, 1.55–10.93; P =.004). Conclusions: In a large, single-center cohort of consecutive patients with cirrhosis and who received DAA treatment for HCV infection, most liver tumors were identified at early stages. Male sex, diabetes, and non-invasive markers of liver fibrosis can be used to identify patients at increased risk for HCC following DAAs therapy.",
keywords = "Direct-Acting Antivirals, HCV, Hepatocellular Carcinoma, IFN-Free Regimens, Predictors",
author = "Elisabetta Degasperi and Roberta D'Ambrosio and Massimo Iavarone and Angelo Sangiovanni and Alessio Aghemo and Roberta Soffredini and Marta Borghi and Giovanna Lunghi and Massimo Colombo and Pietro Lampertico",
year = "2019",
month = "5",
day = "1",
doi = "10.1016/j.cgh.2018.10.038",
language = "English",
volume = "17",
pages = "1183--1191.e7",
journal = "Clinical Gastroenterology and Hepatology",
issn = "1542-3565",
publisher = "W.B. Saunders Ltd",
number = "6",

}

TY - JOUR

T1 - Factors Associated With Increased Risk of De Novo or Recurrent Hepatocellular Carcinoma in Patients With Cirrhosis Treated With Direct-Acting Antivirals for HCV Infection

AU - Degasperi, Elisabetta

AU - D'Ambrosio, Roberta

AU - Iavarone, Massimo

AU - Sangiovanni, Angelo

AU - Aghemo, Alessio

AU - Soffredini, Roberta

AU - Borghi, Marta

AU - Lunghi, Giovanna

AU - Colombo, Massimo

AU - Lampertico, Pietro

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Background & Aims: Patients with cirrhosis and hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs) are still at risk for developing hepatocellular carcinoma (HCC). We aimed to identify features of de novo or recurrent HCCs in these patients, and factors associated with HCC development, in a large cohort of patients with cirrhosis who received treatment with DAAs. Methods: In a retrospective study, we collected data from 565 patients with cirrhosis (median age, 64 years; range, 28–87 years; 60% male, 49% infected with HCV genotype 1; median liver stiffness measurement [LSM], 19.1 kPa; 87% Child-Pugh-Turcotte score A) treated with DAAs at a single center in Italy, from December 2014 through 2016. Cirrhosis was defined based on clinical features, histologic factors (METAVIR F4), or LSM >11.9 kPa. Patients were assessed (complete blood analysis and HCV-RNA quantification) every 4 weeks during treatment; at weeks 4, 12, and 24 afterward; and at 6-month intervals thereafter. HCC surveillance was performed by ultrasound or CT scans every 3–6 months, based on history of HCC. Non-invasive markers of fibrosis, such as ratio of aspartate aminotransferase to platelets, fibrosis-4 (FIB-4) score, and LSMs were assessed. Results: During a median 25 months of follow up (range, 3–39 months), HCC developed in 28/505 patients without a history of HCC (de novo HCC); the 3-year estimated cumulative probability for HCC was 6% (95% CI, 4%–9%). Of patients with de novo HCC, 75% had a single tumor and 82% of these were Barcelona liver cancer stage 0–A; the median level of alpha-fetoprotein was 6 ng/mL (range, 1.0–9240 ng/mL). Male sex (hazard ratio [HR], 6.17; 95% CI, 1.44–26.47; P =.01), diabetes (HR, 2.52; 95% CI, 1.08–5.87; P =.03), LSM (HR, 1.03; 95% CI, 1.01–1.06; P =.01), and FIB-4 score (HR, 1.08; 95% CI, 1.01–1.14; P =.01) were independently associated with de novo HCC. HCC developed in 20/60 patients with a history of HCC (HCC recurrence); the 3-year cumulative probability for recurrence was 43% (95% CI, 20%–61%). In the 20 patients with HCC recurrence, 11 had a single tumor and 90% were Child-Pugh-Turcotte score A. Diabetes was independently associated with HCC recurrence (HR, 4.12; 95% CI, 1.55–10.93; P =.004). Conclusions: In a large, single-center cohort of consecutive patients with cirrhosis and who received DAA treatment for HCV infection, most liver tumors were identified at early stages. Male sex, diabetes, and non-invasive markers of liver fibrosis can be used to identify patients at increased risk for HCC following DAAs therapy.

AB - Background & Aims: Patients with cirrhosis and hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs) are still at risk for developing hepatocellular carcinoma (HCC). We aimed to identify features of de novo or recurrent HCCs in these patients, and factors associated with HCC development, in a large cohort of patients with cirrhosis who received treatment with DAAs. Methods: In a retrospective study, we collected data from 565 patients with cirrhosis (median age, 64 years; range, 28–87 years; 60% male, 49% infected with HCV genotype 1; median liver stiffness measurement [LSM], 19.1 kPa; 87% Child-Pugh-Turcotte score A) treated with DAAs at a single center in Italy, from December 2014 through 2016. Cirrhosis was defined based on clinical features, histologic factors (METAVIR F4), or LSM >11.9 kPa. Patients were assessed (complete blood analysis and HCV-RNA quantification) every 4 weeks during treatment; at weeks 4, 12, and 24 afterward; and at 6-month intervals thereafter. HCC surveillance was performed by ultrasound or CT scans every 3–6 months, based on history of HCC. Non-invasive markers of fibrosis, such as ratio of aspartate aminotransferase to platelets, fibrosis-4 (FIB-4) score, and LSMs were assessed. Results: During a median 25 months of follow up (range, 3–39 months), HCC developed in 28/505 patients without a history of HCC (de novo HCC); the 3-year estimated cumulative probability for HCC was 6% (95% CI, 4%–9%). Of patients with de novo HCC, 75% had a single tumor and 82% of these were Barcelona liver cancer stage 0–A; the median level of alpha-fetoprotein was 6 ng/mL (range, 1.0–9240 ng/mL). Male sex (hazard ratio [HR], 6.17; 95% CI, 1.44–26.47; P =.01), diabetes (HR, 2.52; 95% CI, 1.08–5.87; P =.03), LSM (HR, 1.03; 95% CI, 1.01–1.06; P =.01), and FIB-4 score (HR, 1.08; 95% CI, 1.01–1.14; P =.01) were independently associated with de novo HCC. HCC developed in 20/60 patients with a history of HCC (HCC recurrence); the 3-year cumulative probability for recurrence was 43% (95% CI, 20%–61%). In the 20 patients with HCC recurrence, 11 had a single tumor and 90% were Child-Pugh-Turcotte score A. Diabetes was independently associated with HCC recurrence (HR, 4.12; 95% CI, 1.55–10.93; P =.004). Conclusions: In a large, single-center cohort of consecutive patients with cirrhosis and who received DAA treatment for HCV infection, most liver tumors were identified at early stages. Male sex, diabetes, and non-invasive markers of liver fibrosis can be used to identify patients at increased risk for HCC following DAAs therapy.

KW - Direct-Acting Antivirals

KW - HCV

KW - Hepatocellular Carcinoma

KW - IFN-Free Regimens

KW - Predictors

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U2 - 10.1016/j.cgh.2018.10.038

DO - 10.1016/j.cgh.2018.10.038

M3 - Article

AN - SCOPUS:85064327746

VL - 17

SP - 1183-1191.e7

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

IS - 6

ER -