Interferon (IFN)-free direct antiviral agents (DAAs) effectively eradicate hepatitis C virus (HCV) and rapidly improve liver residual functions. Recent data have suggested that hepatocellular carcinoma (HCC) risk increases during and after DAAs treatment, in HCV-infected patients with advanced liver disease, but no strong evidence exists.
The SCOLTA (Surveillance Cohort Long-Term Toxicity of Antiretrovirals/Antivirals)-HCV project is an observational, prospective, multicenter cohort study enrolling patients, either HCV mono- or HIV/HCV co-infected, who started DAA treatment. For HCV treatment and HCC surveillance, patients were followed according to Italian guidelines.
Overall 1,154 pts were included in this study. Males were 69.2%; median age was 56.2 years. HIV/HCV co-infected were 392 (34.0%). Twenty-nine (2.5%) patients had a history of HCC (24, 3.2%, with HCV and 5, 1.3%, with HCV/HIV). At the time of this analysis, median follow-up from initiation of DAA therapy was 16.7 months (IQR 12.7-19.4). Twenty-seven patients developed HCC, as a first diagnosis in 21 cases and recurrence in 6; the incidence rate/100 patient-years was 1.44 (95% CI 0.92-2.16) and 16.61 (95% CI 6.73-34.55) respectively. HCC was diagnosed during DAA treatment in 10 patients (8 new diagnoses and 2 recurrences). All recurrences occurred in HCV mono-infected patients (5 with SVR 12 and 1 with relapse). Among 21 subjects with first HCC diagnosis, 4 were co-infected with HIV: the rate ratio in comparison with HCV mono-infected patients was 0.43 (95% CI 0.13-1.22, p=0.12). In a multivariate Cox model including age, sex, Metavir, HIV co-infection, HCV genotype, and outcome at 12 weeks, age (HR 1.06, 95% CI 1.01-1.12, by 1 year) and Metavir F4 (HR 4.70, 95% CI 1.08-20.44 as compared to F0-F3) were significantly associated to HCC.
In untreated historical controls, HCC incidence rate ranged between 1 and 3/100 patient-years. Our findings indicate that, in cirrhotic patients, the incidence rate of HCC during the first 16 months following initiation of DAA therapy is not different from that expected in untreated patients.