TY - JOUR
T1 - Undefined/non-malignant hepatic nodules are associated with early occurrence of HCC in DAA-treated patients with HCV-related cirrhosis
AU - Sangiovanni, Angelo
AU - Alimenti, Eleonora
AU - Gattai, Riccardo
AU - Filomia, Roberto
AU - Parente, Elisabetta
AU - Valenti, Luca
AU - Marzi, Luca
AU - Pellegatta, Gaia
AU - Borgia, Guglielmo
AU - Gambato, Martina
AU - Terreni, Natalia
AU - Serio, Ilaria
AU - Belli, Luca
AU - Oliveri, Filippo
AU - Maimone, Sergio
AU - Brunacci, Matteo
AU - D'Ambrosio, Roberta
AU - Forzenigo, Laura Virginia
AU - Russo, Francesco Paolo
AU - Rumi, Mariagrazia
AU - Barone, Michele
AU - Fracanzani, Anna Ludovica
AU - Raimondo, Giovanni
AU - Giannini, Edoardo Giovanni
AU - Brunetto, Maurizia Rossana
AU - Villa, Erica
AU - Biganzoli, Elia
AU - Colombo, Massimo
AU - Lampertico, Pietro
PY - 2020
Y1 - 2020
N2 - Background & Aim: An unexpected early increase in incidence, recurrence and clinical aggressiveness of hepatocellular carcinoma (HCC) has been reported (and refuted) in patients with HCV-related cirrhosis following direct-acting antiviral (DAA) treatment. To address this controversy, we performed a prospective multicenter study on consecutively enrolled cirrhotic patients, with or without a history of HCC, undergoing DAA therapy. Patients and methods: A total of 1,161 HCC-free cirrhotics (group 1) and 124 cirrhotics who had received a curative treatment for an HCC (group 2) were enrolled. Clinical features, including presence of undefined/non-malignant liver nodules (UNMNs), were analyzed with respect to HCC incidence and recurrence. Results: During a median study time of 17 months in group 1 and 16 months in group 2, de novo HCC developed in 48 patients (yearly incidence 3.1/100 patient-years, 75% BCLC 0-A) and recurred in 40 (mean yearly incidence 29.9/100 patient-years, 83% BCLC 0-A). A peak of HCC instant incidence was observed at 4.2 months in group 1 patients with UNMNs, and at 7.7 months in group 2. By multivariable Cox regression models, UNMNs (hazard ratio [HR] 3.11; 95% CI 1.47–6.57: p = 0.003), ascites detected any time before enrolment (HR 3.04; 95% CI 1.23–7.51; p = 0.02), and alpha-fetoprotein log-value (HR 1.90; 95% CI 1.05–3.44; p = 0.03) were the variables independently associated with the incidence of de novo HCC, while history of alcohol abuse (HR 2.10; 95% CI 1.08–4.09; p = 0.03) and history of recurrence of HCC (HR 2.87; 95% CI 1.35–6.09; p = 0.006) were associated with HCC recurrence. Conclusion: An early high incidence of both de novo HCC, in patients with UNMNs, and recurrent HCC was observed in DAA-treated patients; this was not accompanied by increased tumor aggressiveness. Lay summary: This prospective study focuses on the risk of developing de novo or recurrent hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) treatment in patients with hepatitis C-related cirrhosis. We found that DAA treatment was associated with an early high HCC incidence in patients with undefined or non-malignant nodules, as well as in those with a history of complete response to HCC treatment. Whether this is related to the presence of clinically undetectable nests of cancer cells or to precancerous lesions that may progress to overt HCC upon DAA treatment remains unanswered. No evidence of increased clinical aggressiveness was reported in de novo or recurrent HCC.
AB - Background & Aim: An unexpected early increase in incidence, recurrence and clinical aggressiveness of hepatocellular carcinoma (HCC) has been reported (and refuted) in patients with HCV-related cirrhosis following direct-acting antiviral (DAA) treatment. To address this controversy, we performed a prospective multicenter study on consecutively enrolled cirrhotic patients, with or without a history of HCC, undergoing DAA therapy. Patients and methods: A total of 1,161 HCC-free cirrhotics (group 1) and 124 cirrhotics who had received a curative treatment for an HCC (group 2) were enrolled. Clinical features, including presence of undefined/non-malignant liver nodules (UNMNs), were analyzed with respect to HCC incidence and recurrence. Results: During a median study time of 17 months in group 1 and 16 months in group 2, de novo HCC developed in 48 patients (yearly incidence 3.1/100 patient-years, 75% BCLC 0-A) and recurred in 40 (mean yearly incidence 29.9/100 patient-years, 83% BCLC 0-A). A peak of HCC instant incidence was observed at 4.2 months in group 1 patients with UNMNs, and at 7.7 months in group 2. By multivariable Cox regression models, UNMNs (hazard ratio [HR] 3.11; 95% CI 1.47–6.57: p = 0.003), ascites detected any time before enrolment (HR 3.04; 95% CI 1.23–7.51; p = 0.02), and alpha-fetoprotein log-value (HR 1.90; 95% CI 1.05–3.44; p = 0.03) were the variables independently associated with the incidence of de novo HCC, while history of alcohol abuse (HR 2.10; 95% CI 1.08–4.09; p = 0.03) and history of recurrence of HCC (HR 2.87; 95% CI 1.35–6.09; p = 0.006) were associated with HCC recurrence. Conclusion: An early high incidence of both de novo HCC, in patients with UNMNs, and recurrent HCC was observed in DAA-treated patients; this was not accompanied by increased tumor aggressiveness. Lay summary: This prospective study focuses on the risk of developing de novo or recurrent hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) treatment in patients with hepatitis C-related cirrhosis. We found that DAA treatment was associated with an early high HCC incidence in patients with undefined or non-malignant nodules, as well as in those with a history of complete response to HCC treatment. Whether this is related to the presence of clinically undetectable nests of cancer cells or to precancerous lesions that may progress to overt HCC upon DAA treatment remains unanswered. No evidence of increased clinical aggressiveness was reported in de novo or recurrent HCC.
KW - Cirrhosis
KW - Direct-acting antivirals
KW - Hepatocellular carcinoma
KW - Non-malignant liver nodules
KW - Undefined liver nodules
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U2 - 10.1016/j.jhep.2020.03.030
DO - 10.1016/j.jhep.2020.03.030
M3 - Article
C2 - 32243959
AN - SCOPUS:85085680278
VL - 73
SP - 593
EP - 602
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 3
ER -