Self-expanding metal stent should be considered in patients with cirrhosis and uncontrolled variceal bleeding.

SCOPUS: le.jFLWINinfo:eu-repo/semantics/publishe

Liver transplantation for alcoholic hepatitis: A systematic review with meta-analysis.

The rate of alcohol relapse among patients who underwent liver transplantation for alcoholic hepatitis (AH) is not precisely known. Synthesize the available evidence on liver transplantation for AH to assess alcohol relapse and 6-month survival. Meta-analysis of trials evaluating liver transplantation for AH, either clinically severe or diagnosed on the explant. Eleven studies were included. The pooled estimate rate for alcohol relapse was 0.22 (95% CI = 0.12-0.36) in overall analysis with high heterogeneity between studies (I2 = 76%), 0.20 (95% CI = 0.07-0.43) in the subgroup analysis including patients with clinically severe AH (I2 = 84%), 0.14 (95% CI = 0.08-0.23) among patients with clinically severe AH in sensitivity analysis excluding the discrepant studies that did not use stringent selection criteria for liver transplantation (I2 = 0%), and 0.15 (95% CI = 0.07-0.27) for recurrent harmful alcohol consumption among patients with clinically severe AH (I2 = 3%). The risk of alcohol relapse was not different between AH transplanted patients and patients with alcoholic cirrhosis who underwent elective liver transplantation in sensitivity analysis excluding the discrepant studies (OR = 1.68, 95%CI = 0.79-3.58, p = 0.2, I2 = 16%). The pooled estimate rate for 6-month survival was 0.85 (95% CI = 0.77-0.91, I2 = 49%), and 0.80 among patients transplanted for clinically severe AH (95% CI = 0.69-0.88, I2 = 30%). AH transplanted patients had similar 6-month survival to patients with alcoholic cirrhosis who underwent elective liver transplantation (OR = 2.00, 95% CI = 0.95-4.23, p = 0.07, I2 = 0%). Using stringent selection criteria, 14% of patients with clinically severe AH have alcohol relapse after liver transplantation. The percentage of alcohol relapse of AH transplanted patients is similar than that of patients who underwent elective liver transplantation

Intensive enteral nutrition is ineffective for individuals with severe alcoholic hepatitis treated with corticosteroids.

peer reviewedBACKGROUND & AIMS: Severe alcoholic hepatitis (AH) is a lifethreatening disease for which adequate oral nutritional support is recommended. We performed a randomized controlled trial to determine whether the combination of corticosteroid and intensive enteral nutrition therapy is more effective than corticosteroid therapy alone in patients with severe AH. METHODS: We enrolled 136 heavy consumers of alcohol (age, 18–75 y) with recent onset of jaundice and biopsy-proven severe AH in our study, performed at 18 hospitals in Belgium and 2 in France, from February 2010 through February 2013. Subjects were assigned randomly (1:1) to groups that received either intensive enteral nutrition plus methylprednisolone or conventional nutrition plus methylprednisolone (controls). In the intensive enteral nutrition group, enteral nutrition was given via feeding tube for 14 days. The primary end point was patient survival for 6 months. RESULTS: In an intention-to-treat analysis, we found no significant difference between groups in 6-month cumulative mortality: 44.4% of patients died in the intensive enteral nutrition group (95% confidence interval [CI], 32.2%–55.9%) and 52.1% of controls died (95% CI, 39.4%– 63.4%) (P ¼ .406). The enteral feeding tube was withdrawn prematurely from 48.5% of patients, and serious adverse events considered to be related to enteral nutrition occurred in 5 patients. Regardless of group, a greater proportion of patients with a daily calorie intake less than 21.5 kcal/kg/day died (65.8%; 95% CI, 48.8–78.4) than patients with a higher intake of calories (33.1%; 95% CI, 23.1%–43.4%) (P < .001). CONCLUSIONS: In a randomized trial of patients with severe AH treated with corticosteroids, we found that intensive enteral nutrition was difficult to implement and did not increase survival. However, low daily energy intake was associated with greater mortality, so adequate nutritional intake should be a main goal for treatment

Hepatitis B Virus Impairs TLR9 Expression and Function in Plasmacytoid Dendritic Cells

Plasmacytoid dendritic cells (pDCs) play a key role in detecting pathogens by producing large amounts of type I interferon (IFN) by sensing the presence of viral infections through the Toll-Like Receptor (TLR) pathway. TLR9 is a sensor of viral and bacterial DNA motifs and activates the IRF7 transcription factor which leads to type I IFN secretion by pDCs. However, during chronic hepatitis B virus (HBV) infection, pDCs display an impaired ability to secrete IFN-α following ex vivo stimulation with TLR9 ligands. Here we highlight several strategies used by HBV to block IFN-α production through a specific impairment of the TLR9 signaling. Our results show that HBV particle internalisation could inhibit TLR9- but not TLR7-mediated secretion of IFN-α by pDCs. We observed that HBV down-regulated TLR9 transcriptional activity in pDCs and B cells in which TLR9 mRNA and protein levels were reduced. HBV can interfere with TLR9 activity by blocking the MyD88-IRAK4 axis and Sendai virus targeting IRF7 to block IFN-α production. Neutralising CpG motif sequences were identified within HBV DNA genome of genotypes A to H which displayed a suppressive effect on TLR9-immune activation. Moreover, TLR9 mRNA and protein were downregulated in PBMCs from patients with HBV-associated chronic hepatitis and hepatocellular carcinoma. Thus HBV has developed several escape mechanisms to avoid TLR9 activation in both pDCs and B lymphocytes, which may in turn contribute to the establishment and/or persistence of chronic infection

Assessment of the risk of alcohol relapse following liver transplantation for alcoholic hepatitis using a meta-analysis approach.

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Rôle de la glycosylation des protéines d’enveloppe dans la morphogenèse des Flaviviridae et son inhibition par des antiviraux de nouvelles générations

Several viruses of the Flaviviridae family are causing agents of human pathologies, including haemorrhagic fever (e.g. Dengue virus, Yellow fever virus), encephalitis (e.g. Japanese encephalitis virus), or chronic hepatitis (Hepatitis C virus). For most of these diseases, while no vaccine have been developed to date, either no or non optimal treatments are currently available. New antivirals are needed to better combat Flaviviridae induced diseases. Molecules targeting specifically viral enzymes are the most attractive in terms of drug development and are therefore the most studied. However, an antiviral strategy based uniquely on the utilisation of this type of molecules is expected to encounter problems caused by the emergence of viral escape mutants, as already widely described for HIV and HBV. Alternative approaches would include targeting either a viral function that is less likely to give rise to viral escape mutants, or a host cell encoded function that would be crucial for the virus, but not for the cell itself. The viral assembly and morphogenesis belong to these new potential targets yet not exploited. Recently inhibitors of morphogenesis have been identified and studied in different virus/cell systems. Some of them are currently evaluated in clinical trials against HCV. The present review focuses on the Flaviviridae morphogenesis and its inhibition; and presents clinical development perspectives of this new generation of antivirals.La famille des Flaviviridae regroupe des virus enveloppés à ARN simple brin de polarité positive responsables de nombreuses pathologies humaines et animales. Trois genres constituent cette famille : le genre des flavivirus qui comprend, entre autres, les virus West Nile (WNV), de la fièvre jaune (YFV), de la dengue (DEN), de l’encéphalite japonaise (JEV) et de l’encéphalite transmise par les tiques (TBE) ; celui des pestivirus qui inclut les virus de la diarrhée bovine (VDBV), un virus souvent utilisé comme modèle d’étude du HCV et de la peste porcine classique (CSFV) et, enfin, le genre des hépacivirus qui comprend notamment les différents génotypes et sous-types du virus de l’hépatite C (HCV) [1]. En dépit de leur impact sur la santé humaine, il n’existe pas à l’heure actuelle de traitements antiviraux spécifiques et efficaces pour combattre les infections à flavivirus. En ce qui concerne les infections liées au HCV, un traitement associant l’interféron alpha (IFNα) et la ribavirine permet d’obtenir un taux élevé de réponse virologique prolongée (50-60 %) [2]. Cependant, ce traitement est assez mal toléré en raison des nombreux effets secondaires et, de plus, est très onéreux, ce qui limite son utilisation aux pays développés. Par conséquent, il est urgent et indispensable de développer de nouveaux antiviraux afin de mieux combattre les infections liées aux Flaviviridae. La morphogenèse est une étape clé du cycle viral et représente par conséquent une cible intéressante, encore non exploitée, pour le développement de nouvelles stratégies antivirales. Récemment, des molécules inhibant la morphogenèse virale ont été identifiées et leurs mécanismes d’action étudiés en systèmes cellulaires et animaux. Certaines de ces molécules ont été évaluées ou sont en cours d’évaluation dans le cadre d’essais cliniques sur l’homme. L’objectif de cette revue est de faire un bref état des lieux sur la morphogenèse des Flaviviridae et son inhibition par des antiviraux de nouvelles générations

Rôle de la glycosylation des protéines d'enveloppe dans la morphogenèse des Flaviviridae et son inhibition par des antiviraux de nouvelles générations

Several viruses of the Flaviviridae family are causing agents of human pathologies, including haemorrhagic fever (e.g. Dengue virus, Yellow fever virus), encephalitis (e.g. Japanese encephalitis virus), or chronic hepatitis (Hepatitis C virus). For most of these diseases, while no vaccine have been developed to date, either no or non optimal treatments are currently available. New antivirals are needed to better combat Flaviviridae induced diseases. Molecules targeting specifically viral enzymes are the most attractive in terms of drug development and are therefore the most studied. However, an antiviral strategy based uniquely on the utilisation of this type of molecules is expected to encounter problems caused by the emergence of viral escape mutants, as already widely described for HIV and HBV. Alternative approaches would include targeting either a viral function that is less likely to give rise to viral escape mutants, or a host cell encoded function that would be crucial for the virus, but not for the cell itself. The viral assembly and morphogenesis belong to these new potential targets yet not exploited. Recently inhibitors of morphogenesis have been identified and studied in different virus\cell systems. Some of them are currently evaluated in clinical trials against HCV. The present review focuses on the Flaviviridae morphogenesis and its inhibition ; and presents clinical development perspectives of this new generation of antivirals