Introduction: Within the past decade, antiviral treatment for chronic hepatitis C virus (HCV) infection has evolved from interferon (IFN)-based regimens to IFN-free oral direct-acting antiviral agents (DAAs). However, data on long-term outcomes in HCV patients treated by DAAs are limited and complex. Areas covered: Original studies and meta-analyses reporting data on the impacts of IFN – and DAA-based treatments on late relapse, liver fibrosis/cirrhosis, decompensation progression, hepatocellular carcinoma (HCC) occurrence and recurrence, need for liver transplantation, mortality, and other topics of interest for long-term observation of HCV patients treated with DAAs. Articles published up to June 2018, and proceedings from annual meetings of major international liver diseases associations (from 2015 to June 2018) were reviewed. Relevant references from selected papers were also reviewed. Expert opinion: In HCV patients treated with DAAs or IFN-based regimens, late relapse beyond 12 weeks after completion of treatment is uncommon. Results from long-term follow-up studies suggest responders to antiviral treatment achieve benefits on regression of fibrosis/cirrhosis, decreasing risk of progression to liver decompensation, reductions in the need for liver transplantation and mortality. Well-designed studies with robust comparisons are needed to determine the effect of DAAs on the recurrence of HCC in the future.