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Background Clinical decompensation of cirrhosis is associated with poor prognosis. Clinically significant portal hypertension (CSPH), defined by a hepatic venous pressure gradient (HVPG) >= 10 mm Hg, is the strongest predictor of decompensation. This study aimed at assessing whether lowering HVPG with beta blockers could decrease the risk of decompensation or death in compensated cirrhosis with CSPH. Methods This study on beta blockers to prevent decompensation of cirrhosis with portal hypertension (PREDESCI) was an investigator-initiated, double-blind, randomised controlled trial done in eight hospitals in Spain. We enrolled patients with compensated cirrhosis and CSPH without high-risk varices. All participants had HVPG measurements with assessment of acute HVPG-response to intravenous propranolol. Responders (HVPG-decrease >= 10%) were randomly assigned to propranolol (up to 160 mg twice a day) versus placebo and non-responders to carvedilol (

This article reviews the different acute and chronic neurological manifestations of excessive alcohol consumption that affect the central or peripheral nervous system. Several mechanisms can be implicated depending on the disorder, ranging from nutritional factors, alcohol-related toxicity, metabolic changes and immune-mediated mechanisms. Recognition and early treatment of these manifestations is essential given their association with high morbidity and significantly increased mortality. (C) 2017 Elsevier Espana, S.L.U., AEEH y AEG. All rights reserved.

In many countries, first-generation protease inhibitors (PIs)/peginterferon/ribavirin (P/R) still represent the only treatment option for HCV-infected patients. Subjects with advanced disease and previous failure to P/R urgently need therapy, but they are under-represented in clinical trials. All treatment-experienced F3/4 Metavir patients who received boceprevir (BOC)+P/R in the Italian-Spanish Name Patient Program have been included in this study. Multivariate logistic regression analysis (MLR) was used to identify baseline and on-treatment predictors of SVR and adverse events (AEs). Four hundred and sixteen patients, mean age 57.7 (range 25-78 years), 70% males, 69.5% (289/416) F4, 14% (41/289) Child-Pugh class A6, 24% (70/289) with varices and 42% (173/416) prior null responders to P/R, were analysed. Overall, SVR rate (all 381 patients who received one dose of BOC) was 49%, (58% in F3, 45% in F4, 61% in relapsers, 51% in partial, 38% in null responders, and 72% in subjects with undetectable HCV-RNA at treatment-week (TW)8. Among patients with TW8 HCV-RNA ≥ 1000 IU/L, SVR was 8% (negative predictive value = 92%). Death occurred in 3 (0.8%) patients, while decompensation and infections were observed in 2.9% and 11%, respectively. At MLR, SVR predictors were TW4 HCV-RNA ≥ 1log10 -decline from baseline, undetectable TW8 HCV-RNA, prior relapse, albumin levels ≥3.5 g/dL and platelet counts ≥100 000/μL. Metavir F4, Child-Pugh A6, albumin, platelets, age and female gender were associated with serious and haematological AEs. Among treatment-experienced patients with advanced liver disease eligible for IFN-based therapy, TW8 HCV-RNA characterised the subset with either high or poor likelihood of achieving SVR. Using TW8 HCV-RNA as a futility rule, BOC/P/R appears to have a favourable benefit-risk profile.

Aliment Pharmacol Ther 31, 834–845 Summary Background There is little information on the effects of vaptans in patients with cirrhosis. Aim To investigate the short-term effects of satavaptan, a selective vasopressin V2 receptor antagonist on ascites in cirrhosis without hyponatraemia. Methods A total of 148 patients with cirrhosis, ascites and serum sodium >130 mmol/L were included in a multicentre, double-blind, randomized, controlled study of 14 days comparing three fixed doses of satavaptan (5 mg, 12.5 mg or 25 mg once daily) vs. placebo. Average MELD scores were: 13.4, 12.3, 13.8 and 13.1 respectively. All patients received spironolactone 100 mg/day plus furosemide 20–25 mg/day. Results Satavaptan treatment was associated with a decrease in ascites (mean change in body weight was −0.36 kg (±3.03) for placebo vs. −2.46 kg (±3.11), −2.08 kg (±4.17) and −2.28 kg (±3.24) for the 5 mg, 12.5 mg and 25 mg doses respectively; P = 0.036, P = 0.041 and P = 0.036 for satavaptan 5, 12.5 and 25 mg/day vs. placebo respectively). Thirst and slight increases in serum sodium were more common in patients treated with satavaptan compared with placebo, while other adverse events were similar. Conclusions The administration satavaptan for a 14-day period is associated with reduction in ascites in patients with moderately severe cirrhosis without hyponatraemia under diuretic treatment.

BACKGROUND: Patients infected with hepatitis C virus (HCV) genotype 2 or 3 have sustained virologic response rates of approximately 80% after receiving treatment with peginterferon and ribavirin for 24 weeks. We conducted a large, randomized, multinational, noninferiority trial to determine whether similar efficacy could be achieved with only 16 weeks of treatment with peginterferon alfa-2a and ribavirin. METHODS: We randomly assigned 1469 patients with HCV genotype 2 or 3 to receive 180 mug of peginterferon alfa-2a weekly, plus 800 mg of ribavirin daily, for either 16 or 24 weeks. A sustained virologic response was defined as an undetectable serum HCV RNA level (

Half of the patients chronically infected with hepatitis C virus (HCV) genotype 1 fail to respond to pegylated interferon alpha (PEG-IFN) and ribavirin (RBV) therapy. This study assesses the effects of treatment on the evolution of the E1-E2 viral region in non-responder patients infected with HCV-1b. Twenty-three HCV-1b chronically infected patients were studied retrospectively, including 19 non-responders to PEG-IFN/RBV therapy (11 null-responders and 8 relapsers) in the study group, and 4 untreated patients in the control group. Genetic and phylogenetic analyses of the E1-E2 viral populations were performed at baseline and at the time of treatment failure to assess changes in genetic variability and evolutionary dynamics during treatment. Baseline virological characteristics were similar in null-responders, relapsers and controls. E1-E2 genetic variability decreased during treatment in non-responders, with a more pronounced decline in relapsers than in null-responders. A specific evolutionary pattern was not observed in null-responders, while a complete substitution of viral variants found at baseline characterised relapser patients. No specific E1-E2 amino acid substitution involved in treatment failure could be identified. In conclusion, although diverse evolutionary patterns with no apparent common adaptive changes were observed during therapy, treatment failure was characterised by a decline in genetic diversity. (C) 2012 Elsevier B.V. All rights reserved.

This document provides a detailed description of the position of the Catalan Society of Gastroenterology on the accuracy and utility of elastography in the non-invasive diagnosis of liver fibrosis. The document was written by a group of experts in chronic liver diseases and liver transplantation and reflects the consensus reached on the methodology and indications of transient elastography. This document was reviewed and presented in an abbreviated form at the XX Congress of the Catalan Society of Gastroenterology and included on the website http://www.scdigestologia.org/index.php?link=docs_posicio (C) 2011 Elsevier Espana, S.L. All rights reserved.

In this work we discuss two model problems appearing in magneto-hydrodynamics (MHD), namely, the so called full MHD problem and the inductionless MHD problem. The first involves as unknowns the fluid velocity and pressure, the magnetic (induction) field and a pseudo-pressure introduced to impose the zero-divergence restriction of this last unknown. The building blocks of this model are the Stokes problem for the velocity and the pressure and the Maxwell problem for the magnetic field and pseudopressure. We discuss the numerical challenges of the approximation of these two model problems having in mind the need to couple them in the full problem, where additional coupling terms appear. The second model we consider is the inductionless MHD approximation. Instead of the magnetic induction and pseudo-pressure, the magnetic unknowns are now the current density and the electric potential. The building blocks are the Stokes problem for the fluid and the Darcy problem (in primal form) for the current density and electric potential. We discuss also the numerical challenges involved in the approximation of this last problem, particularly considering that it has to be coupled to the former. Once the building blocks have been analysed independently, the possibilities of dealing with the fully coupled problems are discussed. Iterative schemes that can be shown to be stable are presented in the stationary case, showing that a segregated solution for the flow and the magnetic problem is not possible. Most of the results presented are elaborated independently in previous works. Our objective in this paper is to present the different problems with a unified perspective.

Background: Current treatment of chronic hepatitis C virus (HCV) infection has limited efficacy -especially among genotype 1 infected patients-, is costly, and involves severe side effects. Thus, predicting non-response is of major interest for both patient wellbeing and health care expense. At present, treatment cannot be individualized on the basis of any baseline predictor of response. We aimed to identify pre-treatment clinical and virological parameters associated with treatment failure, as well as to assess whether therapy outcome could be predicted at baseline. Methodology: Forty-three HCV subtype 1b (HCV-1b) chronically infected patients treated with pegylated-interferon alpha plus ribavirin were retrospectively studied (21 responders and 22 non-responders). Host (gender, age, weight, transaminase levels, fibrosis stage, and source of infection) and viral-related factors (viral load, and genetic variability in the E1-E2 and Core regions) were assessed. Logistic regression and discriminant analyses were used to develop predictive models. A "leave-one-out" cross-validation method was used to assess the reliability of the discriminant models. Principal Findings: Lower alanine transaminase levels (ALT, p = 0.009), a higher number of quasispecies variants in the E1-E2 region (number of haplotypes, nHap_E1-E2) (p = 0.003), and the absence of both amino acid arginine at position 70 and leucine at position 91 in the Core region (p = 0.039) were significantly associated with treatment failure. Therapy outcome was most accurately predicted by discriminant analysis (90.5% sensitivity and 95.5% specificity, 85.7% sensitivity and 81.8% specificity after cross-validation); the most significant variables included in the predictive model were the Core amino acid pattern, the nHap_E1-E2, and gamma-glutamyl transferase and ALT levels. Conclusions and Significance: Discriminant analysis has been shown as a useful tool to predict treatment outcome using baseline HCV genetic variability and host characteristics. The discriminant models obtained in this study led to accurate predictions in our population of Spanish HCV-1b treatment naive patients.

Hyponatraemia is common in patients with advanced cirrhosis and is associated with remarkable changes in brain cells, particularly a reduction in myoinositol and other intracellular organic osmolytes related to the hypo-osmolality of the extracellular fluid. It has been recently suggested that hyponatraemia may be an important factor associated with the development of overt hepatic encephalopathy (HE). To test this hypothesis, we retrospectively analysed the incidence and predictive factors of overt HE using a database of 70 patients with cirrhosis included in a prospective study comparing transjugular intrahepatic portosystemic shunts (TIPS) vs large-volume paracentesis in the management of refractory of ascites. Variables used in the analysis included age, sex, previous history of HE, treatment assignment (TIPS vs large volume paracentesis plus albumin), treatment with diuretics, serum bilirubin, serum creatinine and serum sodium concentration. Laboratory parameters were measured at entry, at 1 month and every 3 months during follow-up and at the time of development of HE in patients who developed this complication. During a mean follow-up of 10 months, 50 patients (71%) developed 117 episodes of HE. In the whole population of patients, the occurrence of HE was independently associated with serum hyponatraemia, serum bilirubin and serum creatinine. In conclusion, in patients with refractory ascites, the occurrence of HE is related to the impairment of liver and renal function and presence of hyponatraemia.

Introducción: la toxicidad hepática asociada al uso creciente de productos de "remedios naturales" es un fenómeno emergente. Objetivos: valoración de las características epidemiológicas, clínicas y demográficas de los casos de hepatotoxicidad secundarios a productos herbales (PH) y suplementos dietéticos (SD). Pacientes y métodos: análisis de los casos de hepatotoxicidad debida a PH y SD incluidos en el Registro Español de Hepatotoxicidad. Resultados: trece casos de un total de 521 casos (2%) de reacciones adversas hepáticas incluidas en el registro entre 1994 y 2006, eran secundarios a PH/SD, representando el décimo grupo terapéutico responsable por orden de frecuencia, por delante de analgésicos, ansiolíticos y antipsicóticos. Nueve pacientes (69%) eran mujeres y la edad media fue de 45 años. Nueve pacientes (69%) presentaron ictericia. El tipo de daño más frecuente fue el hepatocelular (12; 92%) y un 31% de los casos presentaron datos de hipersensibilidad. La sustancia más comúnmente involucrada en los casos de daño hepático fue la Camellia sinensis (23%) seguida de Rhamnus purshianus e isoflavonas (Fitosoja®, Biosoja®) con dos casos cada uno (15%). Tres casos (23%) presentaron re-exposición positiva. Conclusiones: la hepatotoxicidad originada por PH/SD no es excepcional, y su perfil es la hepatitis aguda hepatocelular ictérica predominantemente en mujeres. La frecuente ocurrencia de reexposición positiva en estos pacientes indica un bajo índice de sospecha y un retraso o ausencia de diagnóstico de este tipo de reacción adversa. Background: toxic liver damage associated with the use of natural remedies is a growing health problem. Objectives: to analyze the demographics, and clinical and epidemiological characteristics of patients developing liver injury related to these remedies. Patients and methods: all DILI cases associated with the use of herbal remedies (HR) or dietary supplements (DS) submitted to the Spanish Registry were analyzed. Type of liver damage, severity, and outcome were specifically evaluated. Results: thirteen cases out of 521 DILI cases (2%) submitted to the Spanish Liver Toxicity Registry between 1994 and 2006 were related to HR/DS, which ranked as the 10th therapeutic group with a greater number of cases and above pain killers, anxiolytics, and antipsychotic drugs. Nine patients (69%) were female (mean age 45 years). Nine cases (69%) had jaundice at presentation. The predominating type of liver damage was hepatocellular (12; 92%), and 31% of cases exhibited the common features of hypersensitivity. Camellia sinensis (3, 23%) was the main causative herb, followed by Rhamnus purshianus and isoflavones (Fitosoja®, Biosoja®) (2 cases each, 15%). Three cases (23%) were rechallenged with the offending product. Conclusions: the incidence of hepatic damage related to HR/DS is not so rare, the most common profile of affected patients being a woman with acute hepatocellular hepatitis. Low suspicion regarding the putative role of herbs in hepatotoxicity makes diagnosis more difficult, and probably increases the incidence of inadvertent rechallenge in these patients.