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.

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Objective: Deficiency of 25-OH Vitamin D (25OHD) and activation of the renin-angiotensin-aldosterone system (RAAS) are both known cardiovascular risk factors. Some studies have shown that 25OHD has a suppressive effect on RAAS but data in literature are conflicting. The aim of the study was to evaluate the relationships between 25OHD level and RAAS parameters in essential hypertensive (EH) patients without obesity and of severe impairment of renal function. Design and method: In 153 EH subjects (age 49 ± 12 years, 87 males, 123 naive, 30 after a wash-out period) we evaluated clinical characteristics, glomerular filtration rate (GFR), plasma levels of 25OHD, 1,25OHD, PTH, potassium, calcium, plasma aldosterone (PA), active renin (AR), angiotensin-converting-enzyme (ACE), 24-h urinary calcium (UCa) and 24-h urinary sodium. Results: 25OHD level was significantly and directly related with UCa (r = 0.209, P = 0.024), ACE (r = 0.470, P < 0.001), PA (r = 0.272, P = 0.001), and inversely related with age (r = -0.301, P < 0.001) and PTH level (r = -0.188, P = 0.025). At multivariate analysis, 25OHD level was independently associated with levels of PTH (B = -0.213, P = 0.023), ACE (B = 0.488, P < 0.001) and PA (B = 0.201, P = 0.039). PA level was positively related with 25OHD, 1,25-OHD (r = 0.256, P = 0.026), and ACE (r = 0.296, P = 0.006) and inversely related with age (r = -0.260, P = 0.019), plasma potassium (r = -0.261, P = 0.001) and alcohol intake (r = -0.224, P = 0.007). In a multivariate model that did not include ACE, PA was independently associated with levels of plasma potassium (B = -0.227, P = 0.004) and 25OHD (B = 0.197, P = 0.018). After inclusion of ACE, PA level remained independently associated only with plasma potassium (B = -0.244, P = 0.015) and alcohol intake (B = -0.244, P = 0.016). At multivariate analysis with ACE as the dependent variable and 25OHD and PA as independent variables, ACE was independently associated with 25OHD level (B = 0.427, P < 0.001). Conclusions: In patients with EH, PA and 25OHD are directly related and this relationship appears to be mediated by the activity of ACE.