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Alcohol-related liver disease (ARLD) is the most prevalent cause of advanced liver disease and liver cirrhosis in Europe, including Spain. According to the World Health Organization the fraction of liver cirrhosis attributable to alcohol use in Spain is 73.8% among men and 56.3% among women. ARLD includes various stages such as steatohepatitis, cirrhosis and hepatocellular cancer. In addition, patients with underlying ARLD and heavy alcohol intake may develop alcoholic hepatitis, which is associated with high mortality. To date, the only effective treatment to treat ARLD is prolonged withdrawal. There are no specific treatments, and the only treatment that increases life expectancy in alcoholic hepatitis is prednisolone. For patients with alcoholic hepatitis who do not respond to treatment, some centres offer the possibility of an early transplant. These clinical practice guidelines aim to propose recommendations on ARLD taking into account their relevance as a cause of advanced chronic liver disease and liver cirrhosis in our setting. This paper aims to answer the key questions for the clinical practice of Gastroenterology, Hepatology, as well as Internal Medicine and Primary Health Centres, making the most up-to-date information regarding the management and treatment of ARLD available to health professionals. These guidelines provide evidence-based recommendations for the clinical management of this disease.

The thermally coupled incompressible inductionless magnetohydrodynamics (MHD) problem models the flow of an electrically charged fluid under the influence of an external electromagnetic field with thermal coupling. This system of partial differential equations is strongly coupled and highly nonlinear for real cases of interest. Therefore, fully implicit time integration schemes are very desirable in order to capture the different physical scales of the problem at hand. However, solving the multiphysics linear systems of equations resulting from such algorithms is a very challenging task which requires efficient and scalable preconditioners. In this work, a new family of recursive block LU preconditioners is designed and tested for solving the thermally coupled inductionless MHD equations. These preconditioners are obtained after splitting the fully coupled matrix into one-physics problems for every variable (velocity, pressure, current density, electric potential and temperature) that can be optimally solved, e.g., using preconditioned domain decomposition algorithms. The main idea is to arrange the original matrix into an (arbitrary) 2 x 2 block matrix, and consider an LU preconditioner obtained by approximating the corresponding Schur complement. For every one of the diagonal blocks in the LU preconditioner, if it involves more than one type of unknowns, we proceed the same way in a recursive fashion. This approach is stated in an abstract way, and can be straightforwardly applied to other multiphysics problems. Further, we precisely explain a flexible and general software design for the code implementation of this type of preconditioners.

Background & Aims: Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Herein, we aimed to uncover the mechanisms of HB pathobiology and to identify new biomarkers and therapeutic targets in a move towards precision medicine for patients with advanced HB. Methods: We performed a comprehensive genomic, transcriptomic and epigenomic characterization of 159 clinically annotated samples from 113 patients with HB, using high-throughput technologies. Results: We discovered a widespread epigenetic footprint of HB that includes hyperediting of the tumor suppressor BLCAP concomitant with a genome-wide dysregulation of RNA editing and the overexpression of mainly non-coding genes of the oncogenic 14q32 DLK1-DIO3 locus. By unsupervised analysis, we identified 2 epigenomic clusters (Epi-CA, Epi-CB) with distinct degrees of DNA hypomethylation and CpG island hypermethylation that are associated with the C1/C2/C2B transcriptomic subtypes. Based on these findings, we defined the first molecular risk stratification of HB (MRS-HB), which encompasses 3 main prognostic categories and improves the current clinical risk stratification approach. The MRS-3 category (28%), defined by strong 14q32 locus expression and Epi-CB methylation features, was characterized by CTNNB1 and NFE2L2 mutations, a progenitor-like phenotype and clinical aggressiveness. Finally, we identified choline kinase alpha as a promising therapeutic target for intermediate and high-risk HBs, as its inhibition in HB cell lines and patient-derived xenografts strongly abrogated tumor growth. Conclusions: These findings provide a detailed insight into the molecular features of HB and could be used to improve current clinical stratification approaches and to develop treatments for patients with HB. Lay summary: Hepatoblastoma is a rare childhood liver cancer that has been understudied. We have used cutting-edge technologies to expand our molecular knowledge of this cancer. Our biological findings can be used to improve clinical management and pave the way for the development of novel therapies for this cancer. (c) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)., This article was possible thanks to the inputs from the Instituto de Salud Carlos III, ISCIII (PI09/00751, PI10/02082, PI13/02340). The project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 668596 (ChiLTERN) and grant agreement No 826121 (iPC). JCR is supported by the Catalan Agency for Management of University and Research Grants (AGAUR, 2019 FI_B01024). LT is supported by an Accelerator Award (CRUCK, AECC, AIRC) (HUNTER, C9380/A26813). DS is supported by the Gilead Research Scholar in Liver Disease. JML is supported by the European Union's Horizon 2020 research and innovation programme (HEPCAR, 667273-2), Institucio Catalana de Recerca i Estudis Avancats (ICREA), U.S. Department of Defense (CA150272P3), an Accelerator Award (CRUCK, AECC, AIRC) (HUNTER, C9380/A26813), National Cancer Institute, Tisch Cancer Institute (P30-CA196521), Samuel Waxman Cancer Research Foundation, Spanish National Health Institute (SAF2016-76390) and AGAUR (SGR-1358). CA and MRS were supported by Ramon y Cajal (RYC-2010-07249) and Miguel Servet (CPII14/00021) programs of the Ministry of Science and Innovation of Spain and ISCIII, respectively. CA, MRS and MS received funding from CIBERehd (CB06/04/0033) and AGAUR (2017-SGR-490). IGTP is a member of the CERCA network of institutes. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Medical imaging is of great importance for patients affected by stroke. Since an early examination of the patient is necessary for successful recovery, there is room to improve the existing capabilities of analysis. Common systems like magnetic resonance imaging or computed tomography are precise, but stationary, and therefore, not ideally suited for the early analysis of stroke. The presented multiport vector network analyzer system uses electromagnetic tomography (EMT) as an alternative imaging technique. It consists of a network of distributed electronic sensor nodes which improve important parameters: the parallel measurement setup reduces the measurement time as low as 160 ms for a 200-port S-parameter matrix and it is capable of measuring signal levels down to − 150 dBm. The electronics allow a compact, movable packaging, leading the way for future portable devices. The detection of stroke models was examined by test measurements of a phantom. The data was analyzed by the help of an inverse reconstruction algorithm. The possibility of building portable setups which can be even applied to patients inside an ambulance, makes EMT a suitable alternative for early stroke detection. It can help in shortening the recovery of patients, by providing an early analysis of the brain.

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.

Resumen En este articulo se revisan las distintas manifestaciones neurologicas del consumo excesivo de alcohol, que pueden ser agudas o cronicas y afectar al sistema nervioso central o periferico. El mecanismo por el cual se producen varia de un grupo de trastornos a otro. Destacan factores nutricionales, efectos toxicos del alcohol, factores metabolicos e incluso inmunologicos. Estas manifestaciones pueden conllevar una gran morbilidad y un aumento significativo de la mortalidad, por lo que es importante reconocerlas y tratarlas precozmente.

Background & Aims: We investigated the efficacy and safety of simeprevir plus daclatasvir in treatment-naïve patients with chronic, genotype 1b hepatitis C virus infection and advanced liver disease, excluding patients with pre-defined NS5A resistance-associated substitutions. Methods: This phase II, open-label, single-arm, multicentre study included patients aged≥18years with advanced fibrosis or compensated cirrhosis (METAVIR F3/4). Patients with NS5A-Y93H or L31M/V resistance-associated substitutions at screening were excluded. Simeprevir (150mg)+daclatasvir (60mg) once daily was administered for 12 or 24weeks; treatment could be extended to 24 weeks prior to or at the Week 12 visit. Primary efficacy endpoint was sustained virological response 12weeks after the end of treatment. Results: A total of 106 patients were treated; 27% patients were aged >65years, 39% had cirrhosis, 53% had estimated glomerular filtration rate 30-89mL/min, 14% had diabetes, and 38% had arterial hypertension. Overall, 42/106 received 12weeks of treatment and 64/106 received 24weeks of treatment. Ninety-seven (92%) patients achieved a sustained virological response 12 weeks after the end of treatment. The reasons for failure were viral breakthrough (n=7) at weeks 4-16, early treatment discontinuation (n=1) and viral relapse (n=1). Seventy-four (70%) patients had ≥1 adverse event during treatment, including six (6%) patients with ≥1 serious adverse event. Three (3%) patients discontinued treatment owing to adverse events. Conclusions: Simeprevir+daclatasvir demonstrated strong antiviral activity and was well-tolerated in patients with hepatitis C virus genotype 1b infection, advanced liver disease and a high prevalence of comorbidities. However, viral breakthrough occurred in seven patients, making this regimen unsatisfactory.

CD5-like (CD5L) is a soluble scavenger cysteine-rich protein that modulates inflammatory responses. We studied the involvement of CD5L in liver cancer. Immunohistochemistry (IHC) of CD5L in 60 hepatocellular carcinomas and 34 adjacent nontumor livers, showed that CD5L staining was higher in tumor than in nontumor tissue (Mann-Whitney test; P = 0.0039). High CD5L correlated with elevated proliferation (Ki67, linear regression; P < 0.0001) and lower patient event-free survival (log-rank; P = 0.0185). Accordingly, CD5L expression was detected in the liver cancer cell lines Huh7, HepG2, and SNU-398. In vitro technologies using these cell lines, including small interfering RNA (siRNA) and cDNA transfection, showed that CD5L promoted colony formation and cell proliferation and protected against cisplatin-induced apoptosis. To find a molecular explanation for these roles, novel CD5L-interacting protein ligands in liver cancer cells were identified by immunoprecipitation followed by mass spectrometry. Among these, the molecular chaperone of the unfolded protein response (UPR), heat shock protein (HSP)-A5, was selected for validation. The interaction was confirmed by confocal microscopy in the Huh7 and HepG2 cell lines. Furthermore, functional experiments revealed that CD5L activates the UPR and autophagy mechanisms in Huh7 cells, thereby providing a novel molecular link between the UPR and autophagy in liver cancer.-Aran, G., Sanjurjo, L., Barcena, C., Simon-Coma, M., Tellez, E., Vazquez-Vitali, M., Garrido, M., Guerra, L., Diaz, E., Ojanguren, I., Elortza, F., Planas, R., Sala, M., Armengol, C., Sarrias, M.-R. CD5L is upregulated in hepatocellular carcinoma and promotes liver cancer cell proliferation and antiapoptotic responses by binding to HSPA5 (GRP78).

ElectroMagnetic Tomography (EMT) is an emerging biomedical imaging modality with great potential for non-invasive assessment of acute and chronic functional and pathological conditions of brain tissue. The mission of EMTensor GmbH is to bring this innovative technology into practical diagnostics of brain, including detection of stroke and traumatic brain injuries, followed by 24/7 monitoring of functional viability of tissue and an assessment of efficacy of treatment. The goal is to create a unique infrastructure based on compact-sized devices, information processing systems and services, which will lead to a breakthrough in brain diagnostics. The idea is to shift the paradigm from a reactive approach, where treatment follows a delayed diagnosis, to a proactive and preventive approach, where early diagnosis leads to successive treatment. The topics of this chapter include a brief introduction of the imaging procedures used at EMTensor GmbH. Furthermore, recent improvements of our image reconstruction algorithms will be discussed briefly, followed by a virtual study to explore the spectrum of potential applications of EMT technology for brain diagnostics. In a next step, the EMTensor BRain IMaging scanner Generation 1 (BRIM G1) will be described. In particular, attention will be given to the imaging results obtained with this scanner in clinical trials. Finally, recent improvements on imaging hardware and chamber topology will be discussed, which have been considered in our second generation brain imaging scanner (BRIM G2).

[Background & Aims] Liver fibrosis is the main determinant of long-term outcome in chronic liver diseases. Little is known about the prevalence of liver fibrosis in the general population. The aim of the study was to investigate the prevalence of liver fibrosis in the general adult population with unknown liver disease., [Methods] This was a population-based, cross-sectional study performed in the Barcelona metropolitan area. Subjects aged 18 to 75 years old were identified randomly from citizens included in the primary health care registry. Of 4866 subjects invited, 3076 participated (63.2%). Liver fibrosis was estimated by measuring liver stiffness (LS) with transient elastography (TE). Liver histology was assessed in 92 subjects with increased LS., [Results] Prevalence estimates of increased LS (≥6.8, ≥8.0, and ≥9.0 kPa) were 9.0%, 5.8%, and 3.6%, respectively. The etiology of liver disease was mainly nonalcoholic fatty liver disease (NAFLD), followed by alcohol risk consumption (consumption of ≥21 standard drinking units/wk in men and ≥14 standard drinking units/wk in women). Factors independently associated with increased LS were male sex, abdominal obesity, type 2 diabetes, serum glucose, high-density lipoprotein, and triglyceride levels. Subjects without risk factors for NAFLD or without alcohol risk consumption had a very low prevalence of increased LS. The best cut-off value of LS for significant liver fibrosis (F2–F4) was 9.2 kPa, with high sensitivity and specificity. TE was more accurate than alanine aminotransferase, NAFLD fibrosis score, or Fibrosis 4. An algorithm for screening for liver fibrosis using TE in the community setting is proposed., [Conclusions] These findings show a high prevalence of silent liver disease with advanced fibrosis mainly related to NAFLD in adult European subjects without known liver disease. An LS value less than 9.2 kPa predicts the absence of significant liver fibrosis with high accuracy and could be used for screening purposes., The project received a research grant from the Carlos III Institute of Health, Ministry of Economy and Competitiveness (Spain), awarded on the 2011 call under the Health Strategy Action 2013–2016, within the National Research Program oriented to Societal Challenges, within the Technical, Scientific and Innovation Research National Plan 2013–2016, with reference PI11/0267, co-funded by European Union European Regional Development Fund funds. Also supported by grants from Fondo de Investigación Sanitaria Instituto de Salud Carlos III-Subdirección General de Evaluación and the European Regional Development Fund Fondo Europeo de Desarrollo Regional (PI16/ 00043), the Agencia de Gestió d’Ajuts Universitarisi de Recerca, and the European Horizon 20/20 program, H20/20-SC1-2016-RTD, and an Institució Catalana de Recerca I Estudis Avançats Academy Award (P.G.).

Background & aims: Decompensated cirrhosis patients have an elevated incidence of early readmission, mortality and economic burden. The aims of HEPACONTROL were to reduce early readmission and to evaluate its impact on mortality and emergency department visits. Patients and methods: Quasi-experimental study with control group which compared two cohorts of patients discharged after being admitted for cirrhosis-related complications. A prospective cohort (n = 80), who followed the HEPACONTROL program, which began with a follow-up examination seven days after discharge at the Hepatology Unit Day Hospital and a retrospective cohort of patients (n = 112), who had been given a standard follow-up. Outcome variables that were compared between both groups were early readmission rates, the number of emergency department visits post-discharge, financial costs and mortality. Results: The rate of early readmission was lower in the group with HEPACONTROL (11.3% vs 29.5%; P = .003). Also, the mean number of visits to the emergency department post-discharge (1.10 +/- 1.64 vs 1.71 +/- 2.36; P = .035), mortality at 60 days (3.8% vs 14.3%; P = .016), and the cost of early readmission were all lower compared with the group with standard follow-up (P = .029). Conclusions: HEPACONTROL decreases the incidence of early readmission the rate of emergency department visits and mortality at 60 days in patients with decompensated cirrhosis, and it is cost-effective. (C) 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Electromagnetic Tomography (EMT) measurement systems with low power consumption, high performance in terms of measurement accuracy and the capability of handling numerous antennas are needed for widely applied EMT. A highly modular approach for such a system is described in this paper. The shown concept allows to measure the required S-parameters, as needed for imaging of attenuative test objects, on any number of antennas simultaneously. This reduces total measurement time, without degradation of measurement accuracy. The presented concept has been realized as a prototype for 32 antennas and experimentally verified using a measurement chamber.

Statistics show, that stroke is one of the main causes of death worldwide, and reliable and fast diagnosis is key to recovery. Modern medical imaging devices provide intricate detail, but lack portability and are in some cases invasive. This paper presents a multiport vector network analyzer (MPVNA) measurement system for electromagnetic tomography (EMT) — an alternative medical imaging technique that complements more established methods. The portability of the system allows stroke to be detected very soon after occurrence. The architecture of the MPVNA enables parallelization of hundreds of measurements, which supports realtime operation without compromising measurement performance. Given the high attenuation caused by the human head and the limited signal power allowed in medical applications, the system is designed to measure signals at power levels as low as −150 dBm.

Background & aims: The early hospital readmission of patients with decompensated cirrhosis is a current problem. A study is presented on the incidence, the impact on mortality, and the predictive factors of early hospital readmission. Patients and methods: On the study included 112 cirrhotic patients, discharged after some decompensation between January 2013 and May 2014. Multivariate analyses were performed to identify predictors of early readmission and mortality. Results: The early readmission rate was 29.5%. The predictive factors were male gender (OR: 2.81; 95% CI: 1.07-7.35), Model for End-Stage Liver Disease-sodium score >= 15 (OR: 3.79; 95% CI 1.48-9.64), and Charlson index >= 7 (OR: 4.34, 95% CI 1.65-11.4). This model enabled patients to be classified into low or high risk of early readmissions (13.6% vs. 52.2%). The mortality rate was significantly higher among patients with early readmission (73% vs. 35%) (p= 15, and Charlson index >= 7 are predictors of early readmission. These results could be used to develop future strategies to reduce early readmission. (C) 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Background & Aims The addition of protease inhibitors (PIs) changed the hepatitis C virus (HCV) treatment standards and improved sustained viral response (SVR) rates in patients with genotype 1 HCV infection. Methods Prospective, multicentre, national registry that includes naive and treatment-experienced patients with HCV genotype 1 infection, who had bridging fibrosis or cirrhosis and were treated with triple therapy (peginterferon alfa-2a or alfa-2b, ribavirin and boceprevir) as compassionate use, and in accordance with the Summary of Product Characteristics. Results Most of the patients (68.2%) were male, with a mean age of 53 years, 75% (n = 128) had HCV 1b genotype and baseline viral load of 6.2 log. According to prior treatment, 20% of patients were treatment-naive and 80% had received prior treatment. Approximately 36.5% of patients (n = 62) reported at least one serious adverse events (SAEs) (total SAEs = 103). The most common SAEs were neutropenia (57.6%), anaemia (47.6%) and grade 3 thrombopenia (25.9%). Patients with albumin 2 mg/dl had an increased relative risk (greater than one-fold) for SAEs, including infections and hepatic decompensation. In the intent-to-treat analysis (n = 170), the overall percentage of patients with SVRw12 was 46.5%. In patients with 1 log decrease at week 4 (lead-in phase), the overall SVRw12 rate was 67.0%. In the patients initiating triple therapy with boceprevir (n = 139), the global response rate was 56.4%. In a multivariate analysis, an increased probability of achieving SVR was associated with response to prior treatment (relapsers), >1 log decrease in viral load in the lead-in phase and baseline albumin >3.5 g/dl. Conclusions Triple therapy in patients with severe fibrosis/cirrhosis is associated with a higher rate of SAE and a lower rate in comparison with patients with mild disease. However, for patients with intact liver function, it could be considered as a treatment option, when other alternatives would not be available.

Chronic infection by the hepatitis B virus (HBV) is a dynamic process that results from the interaction between HBV replication and the host's immune response. In accordance with the consensus document of the European Association for the Study of the Liver, treatment is not indicated for the immune tolerant and inactive carrier phases. However, there are situations in the 2 phases (which we could call gray areas of chronic HBV infection) in which the correct categorization of patients is not easy and in which the start of treatment can be proposed. In the immune tolerant phase, treatment could be indicated for health professionals whose responsibilities require their participation in invasive procedures. Treatment could also be indicated for pregnant women who are HBeAg-positive, ALT normal and have high HBV DNA values and for whom oral antiviral treatment is indicated during the last trimester of pregnancy to reduce the risk of vertical HBV transmission from mother to child. For patients in the inactive carrier phase who are HBeAg-negative with persistent normal ALT levels and HBV DNA ≥ 2000 IU/mL, the intensity of the hepatic lesion will determine the indication for treatment. If these patients already have established cirrhosis then treatment is indicated if the HBV DNA is detectable, regardless of the ALT level.

The first-line option in the treatment of patients with advanced fibrosis and cirrhosis due to genotype 1 hepatitis C virus is currently triple therapy with boceprevir/telaprevir and pegylated interferon-ribavirin. However, certain limitations could constitute a barrier to starting treatment or achieving sustained viral response in these patients. These limitations include the patient's or physician's perception of treatment effectiveness in routine clinical practice-which can weight against the decision to start treatment-, the advanced stage of the disease with portal hypertension and comorbidity, treatment interruption due to poor adherence, and adverse effects, mainly anemia. In addition, it is now possible to identify patients who could benefit from a shorter therapeutic regimen with a similar cure rate. This review discusses these issues and their possible effect on the use of triple therapy.

Objectives The aim of the study was to assess the progression of liver fibrosis in HIV/hepatitis C virus (HCV)-coinfected patients with no or mild-to-moderate fibrosis (stages F0−F2). Methods Liver fibrosis was reassessed by transient elastometry (TE) between January 2009 and November 2011 in HIV/HCV-coinfected patients with stage F0−F2 fibrosis in a liver biopsy performed between January 1997 and December 2007. Patients with liver stiffness at the end of follow-up

Severe alcoholic hepatitis is associated with high early mortality. This study aimed at identifying prognostic factors associated with in-hospital, medium- and long-term mortality of severe alcoholic hepatitis and to evaluate the different prognostic scoring systems on a cohort of patients in our hospital. To this end, we conducted a retrospective analysis of 66 episodes admitted between 2000 and 2008. Clinical and laboratory data on admission, at 7 days, 1 month, 6 months, and after one year were collected and analyzed, as were the details on the treatment and complications that occurred during hospitalization; the different prognostic indices used in the literature were calculated. Death event associated with an episode of severe alcoholic hepatitis occurs primarily during the first month, with an average mortality rate of 16.9. Infectious complications were associated with lower in-hospital survival. MELD score, urea and bilirubin values one week after admission were independently associated with both in-hospital survival (OR = 1.14, 1.012 and 1.1, respectively), and survival at 6 months (OR = 1, 15; 1.014 and 1.016, respectively). Only MELD score and urea values at 7 days were independent predictors of survival twelve months after the acute hepatitis episode. MELD score, urea, and bilirubin 7 days after admission were the only independent in-hospital survival and also long-term survival factors 6 months and one year after the episode. In our cohort, the MELD score was the best prognostic index to predict mortality associated with an episode of severe alcoholic hepatitis.

Triple combination therapy with pegylated interferon, ribavirin and telaprevir is currently considered the gold standard for the treatment of chronic hepatitis C virus (HCV) infection. The most important features are an increase in rates of sustained viral response (74-79% vs 46% with pegylated interferon and ribavirin), as well as the possibility of early cessation of ineffective therapy due to the application of futility rules at weeks 4 and 12 (HCV-RNA > 1,000 UI/ml), and the possibility of selecting candidates for the shortest treatments due to the clinical significance of extended rapid viral response (undetectable HCV-RNA at weeks 4 and 12 of triple therapy). Treatment length is mainly based on the stage of fibrosis and prior response to pegylated interferon and ribavirin. Thus, in both treatment-naive patients and patients with recurrence after pegylated interferon therapy, the duration of treatment is 24 or 48 weeks (unless cirrhosis is present), depending on the presence of extended rapid viral response, while in cirrhotic patients and null responders, treatment length is 48 weeks. The main adverse effects of telaprevir therapy are anemia and skin rash. If these effects occur, the main measures that should be adopted are reduction of the ribavirin dose in anemia, and close monitoring and treatment cessation in skin rash, depending on its spread and severity.

Imaging modalities based on electromagnetic tomography (EMT) have become a field of increasing interest and research in recent years. EMTensor GmbH is focused on the application of EMT technology to detect and identify stroke in human brain. In this work, first imaging results based on a 3D reconstruction of a human head phantom featuring a hemorrhagic stroke model are presented. The results have been obtained with the second generation of EMTensor brain scanner, which uses a spherical chamber topology and 177 ceramic loaded waveguide antennas. This investigation illustrates the ability of EMTensor technology to reconstruct relatively large and highly shielded 3D objects together with small contrast inhomogenities placed inside.

Background: Depression has been associated with higher rates of mortality in medical patients. The aim of the study was to evaluate the impact of depression in medical inpatients on the rate of mortality during a prolonged follow-up period. Method: This is a prospective follow-up study of a cohort of medical inpatients assessed during 1997-1998 in medical and surgical units at a tertiary university hospital in Spain and followed-up for a period ranging between 16.5 and 18 years. Eight hundred three patients were included; 420 (52.3%) were male, and the mean (SD) age was 41.7 (13.8) years. Main outcome was death for any cause during follow-up. The original full Patient HealthQuestionnaire (PHQ) was administered at baseline as self-report from which the PHQ-9 was derived. Depressive disorders were assessed using PHQ-9 and a structured clinical interview (Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition). Results: Depressive disorders as defined by PHQ-9 were detected in 206 patients (25.7%), 122 (15.2%) of them fulfilling criteria for major depression. During follow-up, 152 patients (18.9%) died. A PHQ score indicating the presence of major depressive disorder predicted increased mortality (hazard ratio [HR], 2.44; 95% CI, 1.39-4.29), even after adjusting for important demographic and clinical variables. Similarly, the PHQ-9 score as a continuous measure of depression severity predicted increased mortality (HR, 1.06; 95% CI, 1.02-1.10). Results were similar for clinical interview diagnoses of major depression (HR, 2.07; 95% CI, 1.04-4.09). Conclusions: Medical inpatients with a PHQ depressive disorder had a nearly 2-fold higher risk of long-termmortality, even after adjustment for several confounders. Depression severity as represented by the PHQ-9 score was also a risk factor.

SummaryBackground Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and subsequent hepatocellular carcinoma. HCV genotype 4 is found widely in the Middle East, Egypt and Africa, and has also spread into Europe. There are limited data available regarding the use of direct-acting antiviral agents in HCV genotype 4-infected patients with cirrhosis. Aim The Phase III, open-label, single-arm PLUTO study evaluated the efficacy and safety of 12 weeks of simeprevir (HCV NS3/4A protease inhibitor) plus sofosbuvir (HCV nucleotide-analogue NS5B polymerase inhibitor) in treatment-naive and (peg)interferon ± ribavirin-experienced HCV genotype 4-infected patients, with or without compensated cirrhosis. Methods Adult patients with chronic HCV genotype 4 infection received simeprevir 150 mg once-daily and sofosbuvir 400 mg once-daily for 12 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety was also assessed. Results Forty patients received treatment; the majority were male (73%) and treatment-experienced (68%). Overall, 7/40 (18%) patients had compensated cirrhosis. All patients achieved SVR12 [100% (Clopper-Pearson 95% confidence interval: 91–100%)]. Adverse events, all Grade 1 or 2, were reported in 20/40 (50%) patients. No serious adverse events were reported and no patients discontinued study treatment. Grade 3 treatment-emergent laboratory abnormalities were noted in 2/40 (5%) patients. Conclusions Treatment with simeprevir plus sofosbuvir for 12 weeks resulted in SVR12 rates of 100% in treatment-naive and -experienced patients with HCV genotype 4 infection with or without compensated cirrhosis, and was well tolerated. [NCT02250807]

e154 Volume 37 Number 8S Background: Controlled hypotension during anaesthesia may improve the quality of the surgical field in Ear-Nose-and-Throat (ENT) interventions. A number of drugs are used to that purpose, including alpha-2 adrenergic agonists (A2AA). A systematic review of efficacy data on the use of A2AA as part of hypotensive anaesthesia in ENT has been conducted. Methods: A MEDLINE and Scopus search (1980-2015) was done to identify clinical trials comparing an A2AA as a part of hypotensive anaesthesia regimen in ENT. Additional references were identified through cross-link references. Abstracts were reviewed by two investigators for eligibility, and full papers were fully reviewed if reporting randomised trials comparing A2AA in adult patients undergoing ENT surgery. Data was extracted and synthesized for studied population, surgical procedure, type of anaesthesia, treatments compared, bleeding results and overall report quality. Due to heterogeneity in variables, synthesis of data was based on a qualitative description of trials characteristics, and also of results on the assessments of surgical field bleeding, because of the heterogeneity in the type of variables used for its assessment. Results: A total of 79 publications were identified, from which 22 randomised clinical trials were selected (15 double-blind, 4 singleblind and 3 open-label) including information on 1278 patients undergoing either nasal, sinusal or ear surgeries and comparing A2AA (clonidine (n = 11) or dexmedetomidine (n = 11)) with placebo (n = 9), remifentanil (n = 3), esmolol (n = 2), midazolam (n = 2), magnesium sulphate (n = 2), fentanyl (n = 1) or no treatment (n = 3). Sixteen trials including 1168 patients measured surgical field bleeding, of which 14 showed better results for A2AA. None of the studies compared directly clonidine and dexmedetomidine. Conclusions: Alpha-2 adrenergic agonists have repeatedly shown to improve surgical field bleeding during ENT surgery; there are no comparative data between different A2AA.

SUMMARY In this article, we propose different splitting procedures for the transient incompressible magnetohydrodynamics (MHD) system that are unconditionally stable. We consider two levels of splitting, on one side we perform the segregation of the fluid pressure and magnetic pseudo-pressure from the vectorial fields computation. At the second level, the fluid velocity and induction fields are also decoupled. This way, we transform a fully coupled indefinite multi-physics system into a set of smaller definite ones, clearly reducing the CPU cost. With regard to the finite element approximation, we stick to an unconditionally convergent stabilized finite element formulation because it introduces convection stabilization, allows to circumvent inf-sup conditions (clearly simplifying implementation issues), and is able to capture non-smooth solutions of the magnetic subproblem. However, residual-based finite element formulations are not suitable for segregation, because they lose the skew-symmetry of the off-diagonal blocks. Therefore, in this work, we have proposed a novel term-by-term stabilization of the MHD system based on projections that is still unconditionally convergent. Copyright © 2012 John Wiley & Sons, Ltd.

Se estima en un 1,5-2% la poblacion espanola infectada por el virus de la hepatitis C, el 75% de la cual no esta diagnosticada. Dado que es la causa mas frecuente de cirrosis hepatica y de carcinoma hepatocelular, el papel del medico de familia es basico para su deteccion precoz de cara a iniciar medidas preventivas y terapeuticas dirigidas a controlar la evolucion de la enfermedad.

Background Prognosis of decompensated alcoholic cirrhosis is based mainly on studies that included patients with different severities of liver disease and did not recognize either hepatitis C virus epidemic or changes in clinical management of cirrhosis. Aim To define the long-term course after the first hepatic decompensation in alcoholic cirrhosis. Methods Prospective inclusion at the start point of decompensated cirrhosis of 165 consecutive patients with alcoholic cirrhosis without known hepatocellular carcinoma hospitalized from January 1998 to December 2001 was made. Follow-up was maintained until death or the end of the observation period (April 1, 2010). Results The patients were followed for 835.75 patient years. Median age was 56 years (95% confidence interval: 54-58). Baseline Child-Pugh score was 9 (95% CI: 8-9), and model for end-stage liver disease (MELD) was 13.8 (95% CI: 12.5-14.7). Ascites was the most frequent first decompensation (51%). During follow-up, 99 (60%) patients were abstinent, hepatocellular carcinoma developed in 18 (11%) patients, and 116 patients died (70%). Median overall survival was 61 months (95% CI: 48-74). Median survival probability after onset of hepatic encephalopathy (HE) was only 14 months (95% CI: 5-23). Age, baseline MELD, albumin, development of HE, and persistence of alcohol use were independently correlated with mortality. Conclusions Patients with alcoholic cirrhosis show a high frequency of complications. The low mortality rate in our cohort of patients probably reflects the improvement in the management of patients with cirrhosis; it is mainly influenced by baseline MELD, age, HE development, and continued abstinence. Patients who develop HE should be considered for hepatic transplantation.

Summary Objective One of the side effects of interferon-alpha (IFN-α) therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT remains to be defined. The aim of this study was to assess different peripheral blood lymphocyte subpopulations, mainly CD4+CD25+CD127low/-FoxP3+ regulatory T cells (Tregs), in patients with chronic hepatitis C virus (HCV) infection who developed IIT. Design, patients and methods From 120 patients with chronic HCV who started antiviral treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-HCV). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment (PT) and at appearance of IIT (TT). Results Eleven patients developed IIT: three Hashimoto’s thyroiditis, one Graves’disease, one positive antithyroidal antibodies, one nonautoimmune hypothyroidism and five destructive thyroiditis. During antiviral treatment, an increase in CD8+ and in Tregs was observed in both groups. A decrease in CD3+, CD19+ and NKT lymphocyte subpopulations was also observed (all P

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.

Resolution of hepatitis C virus (HCV) infection requires a complex interplay between innate and adaptative immune responses. The role of lymphocyte subpopulations during combined antiviral treatment remains to be defined. This study was conducted to assess the effect of pegylated interferon-alpha2a (pegIFN-α2a) and ribavirin treatment on peripheral blood lymphocytes, mainly on CD81 expression on B cells and CD4(+) CD25(+) CD127(low/-) FoxP3(+) regulatory T cells (Tregs) in patients with chronic HCV infection. Thirty-five patients with chronic HCV infection who started pegIFN-α2a and ribavirin treatment were enrolled. Peripheral blood mononuclear cells (PBMC) were obtained at baseline before treatment (BT), mid-treatment (MT), the end of treatment (ET) and 24weeks post-treatment (PT). During combined antiviral treatment, a significant decrease in the percentage of CD3(+) , CD8(+) , CD3(+) gamma/delta (γδ)(+) , CD19(+) lymphocyte subpopulations and Tregs was observed. There was also a significant increase in the percentage of the CD4(+) lymphocyte subpopulation and in CD81 expression levels on CD19(+) B cells when BT was compared with ET (all P

In this work, we present a stabilized formulation to solve the inductionlessmagnetohydrodynamic(MHD) problem using the finite element(FE) method. The MHD problem couples the Navier–Stokes equations and a Darcy-type system for the electric potential via Lorentz’s force in themomentum equationof the Navier–Stokes equations and the currents generated by the moving fluid in Ohm’s law. The key feature of the FE formulation resides in the design of the stabilization terms, which serve several purposes. First, the formulation is suitable for convection dominated flows. Second, there is no need to useinterpolationspaces constrained to acompatibility conditionin both sub-problems and therefore, equal-order interpolation spaces can be used for all the unknowns. Finally, this formulation leads to a coupledlinear system; this monolithic approach is effective, since the coupling can be dealt by effective preconditioning and iterative solvers that allows to deal with high Hartmann numbers.

Resumen La encefalopatia hepatica (EH) es una complicacion frecuente de la cirrosis, con un gran impacto social, que deteriora la calidad de vida del paciente y se considera un signo de enfermedad hepatica avanzada y, por tanto, una indicacion clinica para la evaluacion de trasplante hepatico. Los pacientes que han presentado episodios de EH tienen un elevado riesgo de recurrencia, por lo que una vez superado el episodio de EH se recomienda el control y la prevencion de factores precipitantes (hemorragia digestiva, peritonitis bacteriana espontanea, uso de los diureticos con precaucion, evitar medicacion depresora del sistema nervioso), la administracion continuada de disacaridos no absorbibles, como lactitol o lactulosa, o de antibioticos poco o no absorbibles como rifaximina, y la valoracion de la necesidad de un trasplante hepatico, dado que la presencia de un episodio de EH conlleva un mal pronostico en la cirrosis.

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.

This study has been supported by a grant from the Fondo de Investigaciones Sanitarias (Instituto de Salud Carlos III, FIS 051371). Ciberehd is funded by the Instituto de Salud Carlos III.

Summary Background & aims Prophylaxis of bacterial infections in cirrhosis is based on the administration of non-absorbable antibiotics to decontaminate the gut and to avoid intestinal bacterial translocation, leading to the appearance of resistances. We assessed the usefulness of the probiotic Lactobacillus fermentum CECT 5716 on the incidence of intestinal bacterial translocation in ascitic cirrhotic rats. Methods 27 rats with CCL4-induced cirrhosis and 16 healthy rats were treated with L. fermentum CECT 5716 (109 UFC/day) or placebo as follows: cirrhosis + probiotic (A, n = 12), cirrhosis (B, n = 15), healthy + probiotic (C, n = 9) and healthy (D, n = 7). After 10 days, mesenteric lymph nodes were obtained as well as caecal content for microbiological cultures, plasma to assess endotoxin and biochemistry parameters and liver for histology. Results Mortality (A: 2/12, B: 5/15) and intestinal bacterial translocation incidence (6/10, 60% in A vs 5/10, 50% in B; p = n.s.) were similar in both groups of cirrhotic rats, A and B. No differences on translocated species were observed. Plasmatic endotoxin decreased significantly in A when compared to B (A: 0.0098 ± 0.006 EU vs B: 0.0434 ± 0.031 EU; p Conclusion Oral administration of L. fermentum CECT 5716 has no effect on preventing neither bacterial translocation nor mortality in ascitic cirrhotic rats.