Highlights
- •The study focuses on the risk of developing de novo or recurrent HCC after DAA treatment in patients with HCV cirrhosis.
- •An early peak of HCC incidence was observed in DAA-treated patients.
- •Undefined non-malignant nodules, ascites and AFP were independently associated with the incidence of de novo HCC.
- •History of alcohol abuse and history of previous HCC recurrence were associated with HCC recurrence.
- •No evidence of increased tumour aggressiveness was reported in de novo or recurrent HCC.
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.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: March 31, 2020
Accepted:
March 17,
2020
Received in revised form:
March 16,
2020
Received:
March 4,
2019
Identification
Copyright
© 2020 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.
