Systematic Review With Meta-analysis

Effectiveness of Direct-acting Antiviral Treatment for Hepatitis C in Patients With Hepatocellular Carcinoma

Sichan He; Ian Lockart; Maryam Alavi; Mark Danta; Behzad Hajarizadeh; Gregory J. Dore


Aliment Pharmacol Ther. 2019;51(1):34-52. 

In This Article

Abstract and Introduction


Background: Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection is highly curative and tolerable. Among patients with hepatocellular carcinoma (HCC), optimal timing of DAA therapy remains unclear. Data on efficacy of DAA therapy in patients with HCC would inform this decision-making.

Aim: To evaluate response to DAA therapy among patients diagnosed with HCV infection and HCC.

Methods: Bibliographic databases and conference abstracts were searched. Meta-analysis was conducted to pool sustained virologic response (SVR) estimates.

Results: Fifty-six studies with 5522 patients with HCV and HCC were included. Overall SVR was 88.3% (95% CI 86.1–90.4). Twenty-seven studies included patients with prior or present HCC (n = 3126) and patients without HCC (n = 49 138), in which SVR was 88.2% (95% CI 85.0–91.4) and 92.4% (95% CI 91.1–93.7) among patients with and without HCC, respectively (odds ratio: 0.54, 95% CI 0.43–0.68, P < .001). In the subgroup analyses, higher SVR was seen in patients who received curative HCC management (SVR 90.4%, 95% CI 88.3–92.4), or treated with sofosbuvir + NS5A inhibitor DAAs (SVR 96.9%, 95% CI 94.3–99.4), or in patients with HCV genotype 1 infection (SVR 92.0%, 95% CI 88.1–95.6).

Conclusion: Response to DAA therapy was lower in patients with HCC compared to those without HCC, regardless of cirrhosis status. Among HCC patients, there was an impact of proportion with curative HCC management on DAA therapy response.


Globally, hepatocellular carcinoma (HCC) incidence and mortality continue to rise, with HCC now the third leading cause of cancer-related death.[1] Hepatitis C virus (HCV) infection is a major cause of HCC, with an estimated 167 000 deaths per year from HCV-related HCC in 2015.[2] Treatment of HCV in patients with HCC has the potential to eliminate hepatic inflammation, stabilise liver function and reduce the risk of decompensated cirrhosis.[3,4] Moreover, HCV antiviral treatment can reduce HCC recurrence risk among patients with curative HCC management such as liver transplantation, resection and local ablation.[5,6]

The advent of all-oral direct-acting antiviral (DAA) therapy has transformed HCV management, with high efficacy and tolerability including patients considered in the interferon (IFN)-containing treatment era 'hard to treat' for issues of marginalisation, or comorbidities.[7] Among the comorbidity populations are patients with HCC, who are increasingly receiving DAA therapy.

There are several issues relevant to DAA therapy among patients with HCC. First, initial data suggested a potential increased risk of HCC recurrence,[8–14] although subsequent studies did not support these findings.[15–22] Second, in response to the controversy around HCC recurrence risk, the timing of DAA therapy in relation to HCC management became a point of debate.[23–25] For example, some recommended DAA treatment deferral (ie at least 4–6 months) following potentially curative HCC management.[26–29] Third, the DAA response among patients with HCC is relevant, particularly in relation to optimum timing of initiation. In two cohort studies conducted in the United States, the virological response to DAA therapy was impaired in HCV-related HCC patients, compared to the non-HCC population.[30,31] Furthermore, whether the DAA response in patients with HCC is related to the stage of HCC and/or timing in relation to HCC management is relevant.

The primary goal of this systematic review and meta-analysis was to evaluate the effectiveness of DAA therapy among patients with HCV and a diagnosis of HCC. The secondary goals were to compare DAA virologic response among subpopulations categorised by HCC management, DAA regimen and HCV genotype.