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

Abstract

BACKGROUNDDirect-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 third-generation DAAs against the onset of hepatocellular carcinoma (HCC) and mortality is less well established.AIMTo examine the occurrence of HCC or death from any cause in a retrospective-prospective study of patients treated with DAAs.METHODSPatients 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, alpha-fetoprotein levels, and renal function were considered to be confounders.RESULTSThe incidence rate of HCC in patients with and without SVR was 1.3 and 59 per 100 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).CONCLUSIONDAA 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.

Treatment of chronic hepatitis C-associated cryoglobulinemia vasculitis at the era of direct-acting antivirals

“…5 Patients with CV relapse had more frequently underlying cirrhosis (four of five relapses, 80%). Several months after the end of 20 Importantly, mixed cryoglobulinemia predicted the occurrence of HCC. The persistence of cryoglobulinemia independently of SVR was associated with a higher mortality from any cause (HR: 5.982, p = 0.028 in patients with SVR and HR: 5.633, p = 0.047 in patients without SVR).…”

“…Predictive factors of new HCC occurrence or death from any cause during the follow up were high levels of HCV viremia (HR: 0.808, 95% CI: 0.666-0.980, p = 0.030), platelet count (HR: 0.910, 95% CI: 0.831-0.996, p = 0.041), presence of cryoglobulinemia (HR: 3.460, 95% CI: 1.035-11.56, p = 0.044), and presence of SVR (HR: 0.070, 95% CI: 0.025-0.194, p < 0.001). 20 However, even after SVR and if the fibrosis score decreases during follow up, HCV patients with cirrhosis continue to have a higher risk of HCC (>2%/ year) for many years. Thus, patients with cirrhosis should continue long-term surveillance.…”

“…Colussi et al showed that patients who achieved SVR had a higher survival rate free from HCC than patients who did not reached SVR [hazard ratio (HR): 0.035, 95% CI: 0.015–0.084, p < 0.0001]. 20 Importantly, mixed cryoglobulinemia predicted the occurrence of HCC. The persistence of cryoglobulinemia independently of SVR was associated with a higher mortality from any cause (HR: 5.982, p = 0.028 in patients with SVR and HR: 5.633, p = 0.047 in patients without SVR).…”

Host-Targeting Antivirals for Treatment of Hepatitis C

“…The introduction of DAAs has many positive impacts, through decreasing the incidence of severe hepatic complications and extra-hepatic diseases and reducing hepatitis C-related mortality [51,52]. However, the high cost of DAAs still a barrier to access to therapy [12,53].…”

From cirrhosis to hepatocellular carcinomaAn investigation into hepatitis C viral oncogenesis

“…[8,9] Moreover, new reports showed treatment with DAAs improved survival of HCV infected, even cirrhotic patients. [3,[10][11][12] Despite advancements in treatment in HCC, prognosis remains poor. Predicting which cirrhotic HCV patients will develop HCC remains a challenge.…”