Sustained virologic response to direct-acting antiviral agents predicts better outcomes in hepatitis C virus-infected patients: A retrospective study

BACKGROUND Direct-acting antiviral agents(DAAs) are extremely effective in eradicating hepatitis C virus(HCV) in chronically infected patients. However, the protective role of the sustained virologic response(SVR) achieved by second-and thirdgeneration DAAs against the onset of hepatocellular carcinoma(HCC) and mortality is less well established.AIM To examine the occurrence of HCC or death from any cause in a retrospectiveprospective study of patients treated with DAAs.METHODS Patients were enrolled from a tertiary academic hospital center for liver disease management that collects subject data mainly from northeastern Italy. The study was conducted in 380 patients(age: 60 ± 13 years, 224 males, 32% with cirrhosis)treated with DAAs with or without SVR(95/5%), with a median follow up of 58 wk(interquartile range: 38-117). The baseline anthropometric features, HCV viral load, severity of liver disease, presence of extra-hepatic complications, coinfection with HIV and/or HBV, alcohol consumption, previous interferon use, alphafetoprotein levels, and renal function were considered to be confounders.RESULTS The incidence rate of HCC in patients with and without SVR was 1.3 and 59 per100 person-years, respectively(incidence rate ratio: 44, 95%CI: 15-136, P < 0.001).Considering the combined endpoint of HCC or death from any cause, the hazard ratio(HR) for the SVR patients was 0.070(95%CI: 0.025-0.194, P < 0.001). Other independent predictors of HCC or death were low HCV viremia(HR: 0.808, P =0.030), low platelet count(HR: 0.910, P = 0.041), and presence of mixed cryoglobulinemia(HR: 3.460, P = 0.044). Considering SVR in a multi-state model,the independent predictors of SVR achievement were absence of cirrhosis(HR:0.521, P < 0.001) and high platelet count(HR: 1.019, P = 0.026). Mixed cryoglobulinemia predicted the combined endpoint in patients with and without SVR(HR: 5.982, P = 0.028 and HR: 5.633, P = 0.047, respectively).CONCLUSION DAA treatment is effective in inducing SVR and protecting against HCC or death.A residual risk of HCC persists in patients with advanced liver disease or with complications, such as mixed cryoglobulinemia or renal failure.