Lack of evidence of an effect of direct-acting antivirals on the recurrence of hepatocellular carcinoma: Data from three ANRS cohorts

Abstract

Background & aims: Sustained virological response following interferon-based antiviral treatment of chronic hepatitis C is associated with decreased long-term risk of hepatocellular carcinoma (HCC) in advanced liver fibrosis. An unexpected high rate of HCC recurrence following antiviral treatment using direct-acting antiviral (DAA) has recently been reported.

Methods: We analyzed data individually from three French prospective multicentre ANRS cohorts including more than 6000 patients treated with DAA and we focused on HCC patients who underwent curative procedures before DAA treatment. The aim was to assess the rates of HCC recurrence in these patients according to antiviral treatment regimen.

Results: In the ANRS CO22 "Therapeutic options for hepatitis B and C: a French cohort" (HEPATHER) cohort, 267 patients with chronic hepatitis C who were previously treated for HCC were analyzed, among whom 189 received DAA and 78 did not. The rates of recurrence were 0.73/100 and 0.66/100 person-months, respectively. In the ANRS CO12 "Cirrhose Virale" (CirVir) cohort, 79 cirrhotic patients in whom HCC was diagnosed and treated, 13 received DAA and 66 did not. The rates of recurrence were 1.11/100 and 1.73/100 person-months, respectively. In the ANRS CO23 "Compassionate use of Protease Inhibitors in viral C Liver Transplantation" (CUPILT) Cohort, 314 liver transplant recipients for HCC who were subsequently treated with DAA were analyzed. Seven HCC recurrences were reported after a median time of 70.3months after liver transplantation. The rate of recurrence was 2.2%.

Conclusions: In three distinct prospective cohorts, we did not observe an increased risk of HCC recurrence after DAA treatment, notably in patients who underwent curative HCC treatment including liver transplantation.

Lay summary: Since an unexpected high rate of hepatocellular carcinoma (HCC) recurrence after direct-acting antiviral (DAA) treatment has been suggested in a retrospective study, we analyzed data from three French prospective multicentre ANRS cohorts of >6000 DAA-treated patients who underwent curative HCC therapies. We did not observe an increased risk of HCC recurrence after DAA treatment: the rates of recurrence were similar in treated and untreated patients (0.73/100 and 0.66/100 person-months in in the ANRS CO22 HEPATHER cohort including 189 DAA+ and 78 DAA- and 1.11/100 in 13 DAA+ and 1.73/100 person-months in 66 DAA- in the ANRS CO12 CirVir cohort), respectively. Finally, in the ANRS CO23 CUPILT Cohort, HCC recurred in only 7 among 314 (2.2%) liver transplant recipients for HCC subsequently treated after 70months after liver transplantation.

Keywords: Direct-acting antivirals; Hepatitis C virus; Hepatocellular carcinoma.