Direct-acting antiviral (DAA) therapy may be a beneficial therapy for patients infected with hepatitis C virus (HCV) with a history of hepatocellular carcinoma (HCC) by increasing overall survival, according to a study recently published in Gastroenterology.

HCV infection remains the most common cause of HCC in North America and Europe, and is the third leading cause of cancer-related death worldwide and a leading cause of death in patients with compensated cirrhosis. Because HCC cases occur in the setting of chronic liver disease, prognosis depends on the degree of liver dysfunction and tumor burden. However, patients with HCC are diagnosed at late stages, at which point there are limited treatment options and a median survival of 1 year. Patients who are diagnosed at early stages are eligible for curative treatments, with which the 5-year survival rate approaches 70%.

Several studies have reported a benefit of DAA therapy in reducing incident HCC and mortality among individuals with HCV. However the effect of these therapies on the prognosis of patients who have had a complete response to HCC treatment is less clear because most studies have focused on the association between DAA therapy and cancer recurrence. The association between DAA therapy and overall survival in patients with a history of HCC is less examined. Therefore, this multicenter, retrospective cohort study compared overall survival between patients with HCV infection treated with DAAs and that of patients with HCV infection not treated with DAAs, all of whom previously demonstrated a complete response to HCC therapy.

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In total, 797 patients in 31 healthcare systems throughout the United States and Canada who had HCV-related HCC and who achieved a complete response to resection, local ablation, radiation therapy, or trans-arterial chemoembolization/radioembolization were included. Of these patients, 383 (48.1%) received DAA therapy for HCV and 414 (51.9%) did not after complete response before HCC therapy. To determine the association between receipt of DAA therapy (modeled as a time-varying covariate) and all-cause mortality (accounting for informative censoring and confounding using inverse probability weighting), Cox proportional hazard regression was used.

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Results suggested that DAA therapy was associated with a significant reduction in risk for mortality. Among the patients who received DAAs, there were 43 deaths during 941.0 person-years of follow-up compared with 103 deaths during 526.6 person-years of follow-up in patients who did not receive DAA treatment (crude rate ratio, 0.23). Inverse probability-weighted analyses showed that DAA therapy was associated with a significant reduction in risk for death (hazard ratio, 0.54). However, results suggested that there was no association between survival and DAA therapy among patients who were treated but did not achieve sustained virologic response.

Overall, the study authors concluded that, “[O]ur results suggest use of DAA therapies is likely beneficial in HCV-infected patients with a history of HCC.”


Singal AG, Rich NE, Mehta N, et al. Direct-acting antiviral therapy for HCV infection is associated with increased survival in patients with a history of hepatocellular carcinoma [published online July 30, 2019]. Gastroenterol. doi:10.1053/j.gastro.2019.07.040