Background: There is a controversy regarding the appropriate use of direct acting antivirals (DAAs) in treatment of chronic hepatitis C virus (HCV) in patients with hepatocellular carcinoma (HCC) who were treated radically. Some studies published in 2016 showed increased aggressiveness and rates of HCC recurrence after curative treatment of HCC in HCV patients treated by DAAs who achieved sustained virological response (SVR). On the other hand, the ANRS study, did not show any increased risk of HCC recurrence in the same population of patients. This led to the conduction of this trial to shed some light on this debate.
Aim of work: Assess the recurrence rate of HCC in HCV infected patients who received curative treatment for HCC and achieved radiological complete response (rCR) with and without administration of DAAs and assess the effect of the timing of its administration.
Patients and methods: Open labeled, prospective, randomized, controlled, phase 3 study in which patients with HCV and prior history of treated HCC who achieved rCR were randomized to receive DAAs or not. Patients in the arm receiving DAAs are further subdivided into 2 groups, one receiving DAAs within 6 months, and the other after 6 months. Primary end point is recurrence rate of HCC in the two main randomized arms. Secondary end point is identification of predictive factors of HCC recurrence in chronic HCV patients treated with DAAs and achieved SVR.
Results: Eighty patients with rCR of HCC after curative treatment who met the inclusion criteria were randomly assigned in the 2 arms, 40 to DAAs based treatment arm and 40 to be kept on follow up. Interim Analysis showed that the 2-year HCC recurrence rate was lower in DAA treated arm 39.1% versus 42.6% in non DAA treated patients, however it is not statistically significant (P = 0.7223). Post DAA
liver decompensation (P = 0.0212), SVR 12 (P = 0.0193) and ascites (P = 0.0238) were independent predictors of HCC recurrence.
Conclusion: The interim analysis of our study demonstrated that the risk of HCC early recurrence was comparable and not higher than that observed in DAA unexposed patients, and Post DAA liver decompensation, SVR 12 and ascites can be used to stratify the risk of HCC early recurrence, and the efficiency of imaging follow-up. Final analysis of this long-term prospective randomized controlled trial (RCT) is expected to be published within 1 year, aims to assess the impact of DAAs on survival after longer follow up.