Hepatocellular Carcinoma Recurrence in Patients with Chronic Hepatitis C Infection Treated with Direct-Acting Antivirals: A Systematic Review and Meta-Analysis.

Introduction: Reports of direct-acting antivirals (DAA) use for chronic hepatitis C virus (HCV) infection after successful treatment of hepatocellular carcinoma (HCC) have suggested higher rates of HCC recurrence. However, other studies have indicated no increased risk of HCC recurrence.

Methods: To estimate the comparative risk of early HCC recurrence in adults successfully treated for HCC and subsequently treated with interferon (IFN)-free DAAs versus not treated with DAAs for chronic HCV, we conducted a systematic literature review and meta-analysis following established guidelines.

Results: Forty-one cohort studies (10,563 total participants) were identified. The following mutually exclusive comparisons to DAA therapy were determined: IFN-based therapy; no DAA; and no antiviral therapy. Random effects meta-analysis results indicated no increased risk of HCC recurrence with IFN-free DAA therapy when compared with IFN (combined risk ratio (RR) 1.29 [95% CI 0.69, 2.40] at 12 months, 0.88 [95% CI 0.56, 1.39] at 24 months, and 0.67 [95% CI 0.51, 0.88] at longest follow-up), no DAA (combined RR 0.55 [95% CI 0.25, 1.23] at 12 months, 0.67 [95% CI 0.51, 0.86] at 24 months and 0.72 [95% CI 0.61, 0.85] at longest follow-up), or no antiviral therapy (combined RR 0.95 [95% CI 0.76, 1.20] at 12 months, 0.48 [95% CI 0.11, 2.12] at 24 months, and 0.42 [95% CI 0.24, 0.73] at longest follow-up). Results were confirmed in sensitivity analyses.

Conclusions: There is no evidence to suggest that DAA therapy has a higher risk of early HCC recurrence when compared with IFN, no DAA, or no antiviral therapy at any timepoint analyzed. Hence the benefit-risk profile of DAAs in HCV remains positive in relation to the risk of early HCC recurrence.