Effectiveness and safety of sofosbuvir-based regimens plus an NS5A inhibitor for patients with HCV genotype 3 infection and cirrhosis. Results of a multicenter real-life cohort.

Patients with HCV genotype 3 (GT3) infection and cirrhosis are currently the most difficult to cure. We report our experience with sofosbuvir+daclatasvir (SOF+DCV) or sofosbuvir/ledipasvir (SOF/LDV), with or without ribavirin (RBV) in clinical practice in this population. This was a multicenter observational study including cirrhotic patients infected by HCV GT3, treated with sofosbuvir plus an NS5A inhibitor (May 2014-October 2015). In total, 208 patients were included: 98 (47%) treatment-experienced, 42 (20%) decompensated and 55 (27%) MELD score >10. In 131 (63%), treatment was SOF+DCV and in 77 (37%), SOF/LDV. Overall, 86% received RBV. RBV addition and extension to 24 weeks was higher in the SOF/LDV group (95% vs 80%, P=.002 and 83% vs 72%, P=.044, respectively). A higher percentage of decompensated patients were treated with DCV than LDV (25% vs 12%, P=.013). Overall, SVR12 was 93.8% (195/208): 94% with SOF+DCV and 93.5% with SOF/LDV. SVR12 was achieved in 90.5% of decompensated patients. Eleven treatment failures: 10 relapses and one breakthrough. RBV addition did not improve SVR (RR: 1.08; P=.919). The single factor associated with failure to achieve SVR was platelet count <75×10E9/mL (RR: 3.50, P=.019). In patients with MELD <10, type of NS5A inhibitor did not impact on SVR12 (94% vs 97%; adjusted RR: 0.49). Thirteen patients (6.3%) had serious adverse events, including three deaths (1.4%) and one therapy discontinuation (0.5%), higher in decompensated patients (16.7% vs 3.6%, P<.006). In patients with GT3 infection and cirrhosis, SVR12 rates were high with both SOF+DCV and SOF/LDV, with few serious adverse events.

Effectiveness and safety of ombitasvir, paritaprevir, ritonavir ± dasabuvir ± ribavirin: An early access programme for Spanish patients with genotype 1/4 chronic hepatitis C virus infection.

Over the last 5 years, therapies for hepatitis C virus (HCV) infection have improved significantly, achieving sustained virologic response (SVR) rates of up to 100% in clinical trials in patients with HCV genotype 1. We investigated the effectiveness and safety of ombitasvir/paritaprevir/ritonavir±dasabuvir in an early access programme. This was a retrospective, multicentre, national study that included 291 treatment-naïve and treatment-experienced patients with genotype 1 or 4 HCV infection. Most patients (65.3%) were male, and the mean age was 57.5 years. The mean baseline viral load was 6.1 log, 69.8% had HCV 1b genotype, 72.9% had cirrhosis and 34.7% were treatment-naïve. SVR at 12 weeks posttreatment was 96.2%. Four patients had virological failure (1.4%), one leading to discontinuation. There were no statistical differences in virological response according to genotype or liver fibrosis. Thirty patients experienced serious adverse events (SAEs) (10.3%), leading to discontinuation in six cases. Hepatic decompensation was observed in five patients. Four patients died during treatment or follow-up, three of them directly related to liver failure. Multivariate analyses showed a decreased probability of achieving SVR associated with baseline albumin, bilirubin and Child-Pugh score B, and a greater probability of developing SAEs related to age and albumin. This combined therapy was highly effective in clinical practice with an acceptable safety profile and low rates of treatment discontinuation.

Avaliação da atividade antioxidante e alelopática do extrato etanólico e frações das cascas do caule de Zanthoxylum rhoifolium Lam., Rutaceae / Assessment of antioxidant and allelopathic activities of ethanolic extract and solvent fractions from stem bark of Zanthoxylum rhoifolium Lam. (Rutaceae)

The purpose of this study was to test for antioxidantand allelopathic activities in stem bark of Zanthoxylum rhoifolium Lam., Rutaceae, with the eventual aim of discovering biologically active substances. The plant material was subjected to ethanolic extraction and this extract was partitioned, yielding hexane, chloroform, ethyl acetate and hydroalcoholic fractions. Antioxidant activity was estimated by the reduction of phosphomolybdenum complex, of DPPH. and of thiobarbituric acid-reactive substances (TBARS). To detect allelopathy, the samples were tested, at four concentrations, on the germination and development of the radicle and hypocotyl of L. sativa seeds. The samples showed significant antioxidant activity against the reduction of the phosphomolybdenum complex, as compared to rutin, and reduction of TBARS, ascompared to BHT, as well as allelopathic activity, since they stimulated growth and seed germination. The chloroform and ethyl acetate fractions showed the best antioxidant potentials, with 204.17% and 127.11% compared to rutin, in the reduction of phosphomolybdenum complex, as did the crude ethanolic extract and hexane fraction, with 64.2% and 60.9% compared to BHT, in the TBARS method. In the allelopathic assay, the chloroform fraction stood out as the only sample that stimulated the growth of both the radicle and hypocotyl at most concentrations, ranging from 41 to 144%, while the ethyl acetate fraction achieved the greatest stimulus in this bioassay, increasing the growth of the hypocotyl by 274%. This is the first study that demonstrates the antioxidant and allelopathic activities of the species Z. rhoifolium...

Este trabalho teve como objetivo o estudo das atividades antioxidante e alelopática das cascas do caule de Zanthoxylum rhoifolium Lam., Rutaceae, de modo a conduzir à descoberta de substâncias biologicamente ativas. O material vegetal foi submetido à extração etanólica e este extrato foi fracionado obtendo as frações (hexano, clorofórmio, acetato de etila e hidroalcoólica). Para a avaliação da atividade antioxidante, empregaram-se os métodos de redução do complexo fosfomolibdênio, de redução do radical DPPH e das substâncias reativas ao acido tiobarbitúrico (TBARS). Quanto à alelopatia, as amostras foram testadas em quatro concentrações sobre a germinação e o desenvolvimento de radícula e hipocótilo das sementes de Lactuca sativa. As amostras evidenciaram atividade antioxidante significativa frente ao método de redução do complexo fosfomolibdênio quando comparada à rutina, e do TBARS quando comparado ao BHT, assim como a atividade alelopática, uma vez que estimularam tanto a germinação como o crescimento das sementes. A fração clorofórmica e acetato de etila demonstraram melhor potencial antioxidante com 204,17% e 127,11% em relação à rutina no método de formação do complexo fosfomolibdênio, e o extrato bruto e a fração hexano com 64,2% e 60,9%, em relação ao BHT, no método TBARS. No ensaio alelopático, destaca-se a fração clorofórmica, pois foi a única amostra que estimulou o crescimento do hipocótilo e radícula na maioria das concentrações, variando de 41 a 144%, e a fração acetato de etila que apresentou a maior porcentagem de estímulo nesse bioensaio, demonstrando estímulo de 274% do crescimento do hipocótilo. Este é o primeiro trabalho que demonstra a atividade antioxidante e alelopática de Z. rhoifolium...

Meta-analysis: pegylated interferon α-2a achieves higher early virological responses than α-2b in chronic hepatitis C.

BACKGROUND: A Cochrane meta-analysis established that pegylated interferon α-2a is more effective than peginterferon α-2b in terms of sustained virological response (SVR) in the treatment of chronic hepatitis C. Rapid virological response (RVR) and early virological response (EVR) are crucial to reach SVR and to make clinical decisions. AIM: To compare RVR and EVR rates of peginterferon α-2a vs. peginterferon α-2b through a meta-analysis of previously published randomised control trials (RCT). METHODS: MEDLINE, EMBASE and LILACS databases were systematically searched up to September 2011. Seven RCT that reported complete early virological response (cEVR) were selected. A meta-analysis focusing on RVR and cEVR outcomes was conducted and Relative Efficacy (RE) was calculated. RESULTS: Meta-analysis of cEVR included seven trials (n = 4359), and yielded an estimated effect in favour of peginterferon α-2a: Crude Efficacy (CEf) was 53.3% vs. 43.8%, RE = 1.118 (CI 95% = 1.039-1.203; P = 0.0028), heterogeneity Q = 8.959; I² = 33.0% (P = 0.1759). A sub-analysis of three studies with 3409 genotype-1 patients yielded CEf: 49.4% vs. 40.2%, RE = 1.151 (CI 95% = 0.968-1.369; P = 0.1124), Q = 9.802; I² = 79.6% (P = 0.0074). Meta-analysis of RVR included five trials (n = 3833) with an estimated effect in favour of peginterferon α-2a: CEf = 25.0% vs. 16.8%, RE = 1.151 (CI 95%:1.042-1.272; P = 0.0056), Q = 1.461;I² = 0.0% (P = 0.8335). Analysis of four studies reporting RVR including 3499 patients with genotypes 1 and 4 resulted in CEf: 18.3% vs. 12.7% RE = 1.206 (CI 95% = 1.059-1.374; P = 0.0048), Q = 1.116; I² = 0.0% (P = 0.7733). CONCLUSIONS: Peginterferon α-2a may be associated with a higher cEVR and RVR than peginterferon α-2b. These findings could help to achieve higher SVR rates and support clinical decision-making in the present scenario of triple combination therapy.

[Clinical aspects and endoscopic management of gastrointestinal bleeding from Dieulafoy's lesion]. / Aspectos clínicos y tratamiento endoscópico de la hemorragia digestiva por lesión de Dieulafoy.

OBJECTIVE: the aim of the study was to assess the incidence, clinical presentation, location, and response to endoscopic therapy of gastrointestinal bleeding from Dieulafoy's lesion. MATERIAL AND METHOD: ALL consecutive episodes of gastrointestinal bleeding due to Dieulafoy's lesion seen between 2000 and 2006 were retrospectively reviewed. All main clinical and endoscopic data were collected: type and effectiveness of endoscopic therapy, rebleeding, complications, and mortality during hospitalization. RESULTS: WE found 41 patients, 26 males and 15 females, median age of 71.19 years. Dieulafoy's lesion accounted for 1.55% of all gastrointestinal bleeding episodes during the study period. The incidence of Dieulafoy's lesion was 2.2 cases/100.000 inhabitants/year. Active bleeding at endoscopy was present in 85.36%, and comorbidity in 92.68%. The stomach was the most frequent location (60.97%), followed by duodenum (29.26%). Endoscopic therapy achieved initial hemostasis in all cases. Three patients (7.31%) initially treated with epinephrine injection showed rebleeding and properly responded to a second session of endoscopic therapy. No surgery was needed. The mortality rate during hospitalization was 4.87%. CONCLUSIONS: Dieulafoy's lesion is an uncommon, but potentially severe cause of gastrointestinal bleeding. It may be found in any location within the gastrointestinal tract. Endoscopic therapy is effective and safe. Injected epinephrine alone is associated with a higher risk of rebleeding.

Stenosis of the suprahepatic inferior vena cava as a complication of transjugular intrahepatic portosystemic shunt in Budd-Chiari patients.

We report 2 patients with Budd-Chiari (BC) syndrome secondary to thrombogenic conditions who underwent transjugular intrahepatic portosystemic shunt (TIPS) placement because of refractory ascites and impending liver failure. After TIPS placement, there was marked symptomatic relief and improvement in liver function, but the courses of both patients were complicated by the development of an inferior vena cava (IVC) syndrome caused by segmental stenosis of the suprahepatic IVC just at the outflow jet of the TIPS at 11 and 9 months later. One patient underwent liver transplantation, and the other patient, caval angioplasty and stenting. Stenosis of the IVC represents an unrecognized complication of TIPS in patients with BC syndrome.