LAUSR

BACKGROUND & AIMS It is unclear whether direct-acting antiviral (DAA) treatment-induced sustained virologic response (SVR) reduces the risk of hepatocellular carcinoma (HCC) in patients with HCV infection. Therefore, in the current study, our aim was to determine the impact of DAA-induced SVR on HCC risk. METHODS We identified 62,354 patients who initiated antiviral treatment in the Veterans Affairs (VA) national healthcare system from 1 January 1999 to 31 December 2015, including 35,871 (58%) interferon (IFN)-only regimens, 4,535 (7.2%) DAA + IFN regimens, and 21,948 (35%) DAA-only regimens. We retrospectively followed patients until 15 June 2017 to identify incident cases of HCC. We used Cox proportional hazards regression to determine the association between SVR and HCC risk or between type of antiviral regimen (DAA-only vs. DAA + IFN vs. IFN-only) and HCC risk. RESULTS We identified 3,271 incident cases of HCC diagnosed at least 180 days after initiation of antiviral treatment during a mean follow-up of 6.1 years. The incidence of HCC was highest in patients with cirrhosis and treatment failure (3.25 per 100 patient-years), followed by cirrhosis and SVR (1.97), no cirrhosis and treatment failure (0.87), and no cirrhosis and SVR (0.24). SVR was associated with a significantly decreased risk of HCC in multivariable models irrespective of whether the antiviral treatment was DAA-only (adjusted hazard ratio [AHR] 0.29; 95% CI 0.23-0.37), DAA + IFN (AHR 0.48; 95% CI 0.32-0.73) or IFN-only (AHR 0.32; 95% CI 0.28-0.37). Receipt of a DAA-only or DAA + IFN regimen was not associated with increased HCC risk compared with receipt of an IFN-only regimen. CONCLUSIONS DAA-induced SVR is associated with a 71% reduction in HCC risk. Treatment with DAAs is not associated with increased HCC risk compared with treatment with IFN. LAY SUMMARY It was unclear whether direct-acting antiviral treatment-induced sustained virologic response reduces the risk of liver cancer in patients with HCV infection. We demonstrated that eradication of HCV infection with direct-acting antiviral agents reduces the risk of liver cancer by 71%.