Treatment of hepatitis C virus infection in patients with hepatocellular carcinoma: Truth or dare?

The discovery of direct acting antivirals (DAA) with high rates of sustained virusological response is the biggest epoch-making event in the history of hepatitis C virus (HCV) treatment. DAAs improve liver function, prevent hepatic decompensation, and might even reverse liver fibrosis. Although initial research pointed towards a potential drawback, it is now known beyond doubt that DAA treatment reduces hepatocellular carcinoma (HCC) occurrence or recurrence after curative treatments. Unfortunately, the story has reached another plot twist, as several other issues have emerged: (i) Should we treat patients with early HCC and HCV before or after surgery/ablation? (ii) Should patients with HCC on the waiting list receive DAA before or after liver transplantation? (iii) Should we use interferon-free in patients with intermediate stage HCC or in patients under systemic treatments? In this review, we aim to offer some evidence-based answers to these changing clinical dilemmas where possible, or at least some educated guesses in cases were no or little data exists.