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

Abstract

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.

Improved survival and high sustained virologic response with DAA therapy in patients with HCV‐related HCC: A call for expanded use

“…We read with interest the article by Mocan et al 1 regarding antiviral treatment of patients with hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC). We would like to congratulate the authors for their timely and comprehensive review of direct-acting antivirals (DAAs) for HCV in HCC patients.…”

“…First, as described by Mocan et al, 1 tumor cells serving as HCV reservoirs and the tumor microenvironment interfering with the drug distribution can cause lower treatment response rates. However, in a recent systematic review and meta-analysis including 49 studies from 15 countries composed of 3341 HCC and 35 701 non-HCC patients, the pooled global SVR for inactive HCC patients was only mildly lower than those without HCC (92.0%, 95% confidence interval 89.4-94.3% vs 94.5%, 95% confidence interval 93.0-95.9%, P = 0.011).…”

“…3 Meanwhile, active HCC patients had lower SVRs than non-HCC patients (85.5% vs 93.7%, P = 0.03). Therefore, the general approach to HCV-related HCC patients is to treat the tumor first, though the optimal timing of DAA treatment (immediate vs 3 or 6 months after HCC treatment) is still controversial, as discussed by Mocan et al 1 and Ji et al 2 However, in patients with reasonable overall prognoses who are not candidates for HCC therapies due to poor liver function, it may be reasonable to treat HCV first, so that liver function may improve enough to facilitate subsequent HCC therapies, since the lower SVR of 73-85% in patients with active HCC is still a very "respectable" response rate. 2,3 Secondly, and more importantly regarding the effect of DAA treatment on survival, recent well-controlled studies from both East and West have also shown that SVRs with DAA were significantly associated with a more than 60% improvement in both overall and liver-related survival.…”