Early development of de novo hepatocellular carcinoma after direct‐acting agent therapy: Comparison with pegylated interferon‐based therapy in chronic hepatitis C patients

Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct‐acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct‐acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct‐acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct‐acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child‐Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha‐fetoprotein level >9.5 ng/mL at the time of end‐of‐treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P < .0001, hazard ratio 176.174, 95% confidence interval 10.768‐2882.473) and in patients treated with direct‐acting agents (P < .0001, hazard ratio 128.402, 95% confidence interval 8.417‐1958.680). In conclusion, the rate of early development of hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct‐acting antivirals and was associated with the serum alpha‐fetoprotein level at the time of end‐of‐treatment response.