Effectiveness of first-wave protease inhibitors in hepatitis C virus genotype 1 infection: a multicenter study in Brazil

Abstract INTRODUCTION: In 2013, combination therapy using peginterferon, ribavirin, and boceprevir or telaprevir was introduced to treat hepatitis C virus genotype 1 infection in Brazil. The effectiveness of this therapy in four Brazilian regions was evaluated. METHODS: Clinical and virological data were obtained from patients of public health institutions in five cities, including sustained virological response (SVR) and side effects. Patients with advanced fibrosis (F3/4), moderate fibrosis (F2) for > 3 years, or extra-hepatic manifestations were treated according to Ministry of Health protocol. Treatment effectiveness was verified by using bivariate and multivariate analysis; p-values of < 0.05 were considered significant. RESULTS: Of 275 patients (64.7% men; average age, 57 years old), most (61.8%) were treatment-experienced; 53.9% had subgenotype 1a infection, 85.1% had advanced fibrosis, and 85.5% were treated with telaprevir. SVR was observed in 54.2%. Rapid virological response (RVR) was observed in 54.6% of patients (data available for 251 patients). Overall, 87.5% reported side effects and 42.5% did not complete treatment. Skin rash, severe infection, and death occurred in 17.8%, 2.5%, and death in 1.4% of cases, respectively. SVR was associated with treatment completion, RVR, and anemia. CONCLUSIONS: The effectiveness of hepatitis C virus triple therapy was lower than that reported in phase III clinical trials, possibly owing to the prioritized treatment of patients with advanced liver fibrosis. The high frequency of side effects and treatment interruptions observed supported the decision of the Brazilian authorities to suspend its use when safer and more effective drugs became available in 2015.

Crohn's disease activity assessed by doppler sonography: the role of aortic flow parameters

OBJECTIVES: Intestinal neovascularization and abnormal abdominal arterial flow rates have been reported in Crohn's disease. The aim of this study was to evaluate Doppler sonography as a method for assessing Crohn's disease activity based on changes in splanchnic hemodynamics. METHODS: Forty-eight patients with Crohn's disease, 22 healthy volunteers and 12 patients with irritable bowel syndrome were evaluated by Doppler ultrasound for flow parameters of the aorta and superior mesenteric artery. This evaluation included the cross-sectional area, maximum flow volume, peak systolic velocity, end diastolic velocity, resistance and the pulsatility index. Disease activity was classified according to the Crohn's disease activity index. RESULTS: Most measurements in the aorta and superior mesenteric artery were significantly different between Crohn's disease patients and both control groups. Only the aortic maximum flow volume (CC = 0.37, p = 0.009) and aortic peak systolic velocity (CC = 0.30, p = 0.035) showed a significant positive correlation with the Crohn's disease activity index. The determination of cut-off points for the aortic maximum flow volume and peak systolic velocity measurements increased the sensitivity (80 and 75% for flow volume and velocity, respectively), specificity (57 and 75%), accuracy (67 and 75%) and positive (57 and 68%) and negative (80 and 81%) predictive values. These cut-off values permitted the correct classification of most of the patients with Crohn's disease with respect to disease activity. None of the superior mesenteric artery measurements were able to discriminate patients in relation to disease activity. CONCLUSION: The aortic maximum flow volume and peak systolic velocity levels estimated by Doppler sonography reflected disease activity in Crohn's disease. Doppler sonography of the aorta is therefore a novel noninvasive adjunct method that may be ...