Background and Aims: Arrival of direct-acting antiviral (DAA) agents against hepatitis C virus (HCV) with high-sustained virological response (SVR) rates and very few side effects has drastically changed the management of HCV infection. The impact of DAA exposure on hepatocellular carcinoma (HCC) recurrence after a first remission in patients with advanced fibrosis remains to be clarified.

Methods: 68 consecutive HCV patients with a first HCC diagnosis and under remission, subsequently treated or not with a DAA combination, were included. Clinical, biological, and virological data were collected at first HCC diagnosis, at remission and during the surveillance period.

Inclusion Criteria:

• first HCC diagnosed by invasive or non-invasive criteria following the American Association for the Study of Liver Diseases (AASLD) guidelines during the study time horizon
• complete remission after hepatocellular carcinoma treatment defined by the European Association for the Study of the Liver (EASL) criteria as absence of residual tumor/complete necrosis at imaging one month after the end of hepatocellular carcinoma treatment

Exclusion Criteria:

• prior history of hepatocellular carcinoma before January 2009
• liver transplantation before hepatocellular carcinoma diagnosis
• presence of "non-characterized nodules" after hepatocellular carcinoma treatment at imaging
• history of direct-acting antivirals treatment before the first hepatocellular carcinoma diagnosis
• hepatic decompensation
• human immunodeficiency virus (HIV) coinfection.

All HCV infected patients from the Department of Hepatology, Croix-Rousse Hospital, Lyon, France developing a first HCC and receiving or not a direct-acting antiviral combination therapy after HCC remission between January 2009 and March 2016 were considered.