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Mise jour le : 28-05-2017

Les derniers abstracts de la revue Journal of Hepatology :

    Date de mise en ligne : Vendredi 26 mai 2017
    Luiz Eduardo Baggio Savio, Paola de Andrade Mello, Vanessa R. Figliuolo, Thiago F. de Avelar Almeida, Patrícia T. Santana, Suellen D.S. Oliveira, Claudia L.M. Silva, Linda Feldbrügge, Eva Csizmadia, Richard D. Minshall, Maria Serena Longhi, Yan Wu, Simon C. Robson, Robson Coutinho-Silva
    CD39 Limits P2X7 Receptor Inflammatory Signaling and Attenuates Sepsis-Induced Liver Injury
    Sepsis is a leading cause of death in intensive care units worldwide [1] and represents a major public health issue, due to high numbers of deaths of economically productive people and major morbidity in survivors. Aspects of the associated morbidity and mortality are related to onset of shock and hemodynamic compromise with multiple system organ dysfunction and failure due to the excessive, unfettered inflammation [1,2].

    Date de mise en ligne : Vendredi 26 mai 2017
    Toshiaki Teratani, Kengo Tomita, Takahiro Suzuki, Hirotaka Furuhashi, Rie Irie, Shigeaki Hida, Yoshikiyo Okada, Chie Kurihara, Hirotoshi Ebinuma, Nobuhiro Nakamoto, Hidetsugu Saito, Toshifumi Hibi, Soichiro Miura, Ryota Hokari, Takanori Kanai
    Free cholesterol accumulation in liver sinusoidal endothelial cells exacerbates acetaminophen hepatotoxicity via TLR9 signaling
    Acetaminophen (N-acetyl-para-aminophenol [APAP]) is one of the most widely used drugs worldwide owing to its applications in managing pain and hyperthermia; however, APAP occasionally induces liver injury. Consequently, APAP-induced liver injury is the most frequent cause of acute liver failure in the USA and elucidation of the pathological mechanisms of this condition is critical [1].

    Date de mise en ligne : Mardi 23 mai 2017
    Zhen Lu, Bingfeng Zuo, Renwei Jing, Xianjun Gao, Quan Rao, Zhili Liu, Han Qi, Hongxing Guo, HaiFang Yin
    Dendritic cell-derived exosomes elicit tumor regression in autochthonous hepatocellular carcinoma mouse models
    Hepatocellular carcinoma (HCC) presents as one of the most lethal malignancies worldwide due to its aggressive nature, high mortality and low response rates to treatments in the clinic [1]. A multitude of therapeutic approaches are under intensive investigation. Among them, chemotherapeutic and radiotherapeutic interventions have been extensively used, however the survival benefit is limited [2]. Resection surgery is effective for early-stage HCC patients, but is only amenable to a subpopulation of patients and HCC frequently recurs.

    Date de mise en ligne : Lundi 22 mai 2017
    Manuel Romero-Gómez, Shira Zelber-Sagi, Michael Trenell
    Treatment of NAFLD with diet, physical activity and exercise
    Lifestyle intervention can be useful across all the spectrum of NAFLD patients. Losing weight decreases cardiovascular / diabetes risk and also regresses liver disease. Weight reductions of ≥ 10% are required for inducing near universal NASH resolution or fibrosis improvement by at least one stage. However, modest weight losses (>5%) also produce important benefits on NAS and its components. In addition, to improve the success of this intervention we need to explore, beyond total calories and type of weight loss diet, the role of micro and macronutrients, evidence-based benefits of physical activity and exercise and finally supporting these modifications through established behaviour change models and techniques.

    Date de mise en ligne : Vendredi 19 mai 2017
    Lai Wei, David Kung-Chun Chiu, Felice Ho-Ching Tsang, Dicky Cheuk-Ting Law, Carol Lai-Hung Cheng, Sandy Leung-Kuen Au, Joyce Man-Fong Lee, Carmen Chak-Lui Wong, Irene Oi-Lin Ng, Chun-Ming Wong
    Histone methyltransferase G9a promotes liver cancer development by epigenetic silencing of tumor suppressor gene RARRES3
    Deregulation of G9a in human HCC. G9a was frequently up-regulated in human HCC and implicated in HCC tumorigenesis and metastasis. The frequent up-regulation of G9a in human HCC was attributed to gene copy number gain at 6p21 and loss of miR-1. The oncogenic function of G9a was at least partially attributed to the epigenetic silencing of tumor suppressor RARRES3.

    Date de mise en ligne : Vendredi 19 mai 2017
    Julien Calderaro, Gabrielle Couchy, Sandrine Imbeaud, Giuliana Amaddeo, Eric Letouzé, Jean-Frédéric Blanc, Christophe Laurent, Yacine Hajji, Daniel Azoulay, Paulette Bioulac-Sage, Jean-Charles Nault, Jessica Zucman-Rossi
    Histological Subtypes of Hepatocellular Carcinoma Are Related To Gene Mutations and Molecular Tumour Classification
    Malignant primary liver tumours are the second leading cause of cancer-related death worldwide, with an increasing incidence in almost all countries [1]. They are mainly represented by hepatocellular carcinoma (HCC) that results from the malignant transformation of hepatocytes. The most frequent risk factors of HCC comprise alcohol intake, infection by hepatitis B (HBV) or hepatitis C (HCV) viruses, and metabolic syndrome [2]. Although surveillance protocols of patients at-risk to develop HCC have significantly improved, clinical outcome remains poor with a majority of patients presenting with advanced disease not eligible for curative therapy [3].

    Date de mise en ligne : Jeudi 18 mai 2017
    Thomas Pembroke, Marc Deschenes, Bertrand Lebouché, Amine Benmassaoud, Maida Sewitch, Peter Ghali, Philip Wong, Alex Halme, Elise Vuille-Lessard, Costa Pexos, Marina B. Klein, Giada Sebastiani
    Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis
    Hepatic steatosis (HS) is an accumulation of fat into the liver, which may eventually progress to steatohepatitis, a pathologic inflammatory response leading to fibrosis, cirrhosis and liver failure.[1] HS is particularly common in hepatitis C virus (HCV)-infected patients with human immunodeficiency virus (HIV) co-infection, with reported frequencies ranging between 30 and 70%.[2–6] HCV may induce HS through several mechanisms, including altered lipid metabolism, metabolic risk factors in non-genotype 3 infections and a direct steatogenic effect of HCV genotype 3.

    Date de mise en ligne : Jeudi 18 mai 2017
    Lester Suárez-Amarán, Carla Usai, Marianna Di Scala, Cristina Godoy, Yi Ni, Mirja Hommel, Laura Palomo, Víctor Segura, Cristina Olagüe, Africa Vales, Alicia Ruiz-Ripa, Maria Buti, Eduardo Salido, Jesús Prieto, Stephan Urban, Francisco Rodríguez-Frias, Rafael Aldabe, Gloria González-Aseguinolaza
    A new HDV mouse model identifies mitochondrial antiviral signaling protein (MAVS) as a key player in IFN-β induction
    Hepatitis delta virus (HDV), the only member of the genus deltavirus, is a defective RNA virus that requires the surface antigens of hepatitis B virus (HBV) (HBsAg) for viral assembly and transmission and that dictates hepatocyte tropism [1,2]. HBV/HDV co-infection is more frequently associated with severe or fulminant hepatitis, higher risk of cirrhosis and decompensated liver disease, and higher mortality than HBV mono-infection [3–7].

    Date de mise en ligne : Jeudi 18 mai 2017
    Peter Fickert, Gideon M. Hirschfield, Gerald Denk, Hanns-Ulrich Marschall, Istvan Altorjay, Martti Färkkilä, Christoph Schramm, Ulrich Spengler, Roger Chapman, Annika Bergquist, Erik Schrumpf, Frederik Nevens, Palak Trivedi, Florian P. Reiter, Istvan Tornai, Emina Halilbasic, Roland Greinwald, Markus Pröls, Michael P. Manns, Michael Trauner, for the European PSC norUDCA Study Group
    norUrsodeoxycholic Acid Improves Cholestasis in Primary Sclerosing Cholangitis
    Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology characterized by a chronic inflammatory and fibro-obliterative destruction of extra-, and intrahepatic bile ducts [1]. Currently there is no medical therapy with proven benefit on PSC patients’ survival available and the list of drugs tested negative for PSC treatment is long comprising azathioprine, cyclosporine, methotrexate, tacrolimus, penicillamine, cholchicine, and infliximab [2]. Consequently, liver transplantation is the only treatment option for PSC patients with end-stage liver disease.

    Date de mise en ligne : Jeudi 18 mai 2017
    Kristofer Andréasson, Jesper Waldenström, Johan Westin, Hans Norrgren, Göran Jönsson, Kristina Nyström, Martin Lagging
    JHEPAT-D-17-00297 R1: Cartilage oligomeric matrix protein associates with hepatic inflammation and fibrosis in hepatitis C virus infection
    To the Editor:

    Date de mise en ligne : Mercredi 17 mai 2017
    Marina Ruiz de Galarreta, Amaia Lujambio
    Therapeutic editing of hepatocyte genome in vivo
    The recent development of gene editing platforms enables making precise changes in the genome of eukaryotic cells. Programmable nucleases, such as meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)-associated nucleases, have revolutionized the way research is conducted as they facilitate the rapid production of mutant or knock-out cellular and animal models. These same genetic tools can potentially be applied to cure or alleviate a variety of diseases, including genetic diseases that lack an efficient therapy.

    Date de mise en ligne : Mardi 16 mai 2017
    Reiner Wiest, Agustin Albillos, Michael Trauner, Jashmohan Bajaj, Rajiv Jalan
    'Targeting the gut-liver axis in liver disease'
    The gut is open to the outer environment, harbours the microbiome containing several fold more genetic material than the human genome and produces a myriad of metabolites as well as hormones/peptides. The liver is at the nexus between this vast source of nutrients, toxins and hormones and the remaining human body. Not surprisingly, this liver-gut-axis has hence, been demonstrated in experimental models and in-vitro systems to contribute to the pathogenesis of most liver diseases such as alcoholic and non-alcoholic fatty liver disease (NAFLD), -steatohepatitis (NASH), cholestatic liver diseases, hepatocellular carcinoma, acute-on-chronic liver failure, progression to fibrosis/cirrhosis and complications of cirrhosis.

    Date de mise en ligne : Vendredi 12 mai 2017
    Qiuhe Wang, Yong Lv, Ming Bai, Zhengyu Wang, Haibo Liu, Chuangye He, Jing Niu, Wengang Guo, Bohan Luo, Zhanxin Yin, Wei Bai, Hui Chen, Enxin Wang, Dongdong Xia, Xiaomei Li, Jie Yuan, Na Han, Hongwei Cai, Tao Li, Huahong Xie, Jielai Xia, Jianhong Wang, Hongbo Zhang, Kaichun Wu, Daiming Fan, Guohong Han
    Eight millimeter covered TIPS does not compromise shunt function but reduces hepatic encephalopathy in preventing variceal rebleeding
    Since its introduction into clinical practice, transjugular intrahepatic portosystemic shunt (TIPS) has been recommended by guidelines and Baveno consensus [1–7] and widely used in patients with portal hypertension complications not amenable to standard therapy for nearly 30 years [8]. However, no consensus has been reached regarding the key issue of stent diameter selection [5,9] owing to the theoretical dilemma that larger stents would achieve better shunt patency and more sufficient portal decompression but increase the risk of hepatic encephalopathy (HE) or vice versa [10].

    Date de mise en ligne : Vendredi 12 mai 2017
    Vincent Wai-Sun Wong, Salvatore Petta, Jean-Baptiste Hiriart, Calogero Cammà, Grace Lai-Hung Wong, Fabio Marra, Julien Vergniol, Anthony Wing-Hung Chan, Antonino Tuttolomondo, Wassil Merrouche, Henry Lik-Yuen Chan, Brigitte Le Bail, Umberto Arena, Antonio Craxì, Victor de Lédinghen
    Validity criteria for the diagnosis of fatty liver by M probe-based controlled attenuation parameter
    Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide and has become an important cause of end-stage liver disease and hepatocellular carcinoma [1–4]. The presence of fatty liver and metabolic syndrome in patients with chronic viral hepatitis is also associated with increased risk of cirrhosis and hepatocellular carcinoma [5–8]. Abdominal ultrasonography is commonly used to diagnose fatty liver, but it cannot reliably diagnose mild steatosis, and its performance is suboptimal in obese patients.

    Date de mise en ligne : Vendredi 12 mai 2017
    Massimo Colombo, Patrick Maisonneuve
    Controlling liver cancer mortality on a global scale: still a long way to go
    In an era where practice in hepatology has been revolutionised by an avalanche of therapeutic breakthroughs, hepatocellular carcinoma (HCC) still stands as a most difficult to cure end-stage liver disease and the dominant cause of death of patients with compensated cirrhosis of any aetiology [1]. In 2012,the death toll of HCC was impressive, resulting from 521,000 men and 224,500 women estimated to have died from liver cancer, meaning that this cancer was the second leading cause of cancer death in men and the sixth in women, worldwide [2].

    Date de mise en ligne : Mercredi 10 mai 2017
    Ashraf A. Ashhab, Holly Rodin, Jesse Powell, Jose D. Debes
    Hepatocellular carcinoma diagnosis and surveillance: Socioeconomic factors don’t seem to matter, unless you are an immigrant
    Evaluation of factors affecting hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis is an important topic that has been neglected for several years.1 This is surprising considering the heavy burden of HCC-related deaths and the beneficial impact in survival that can be achieved through early detection.2 Several studies this year have attempted to define factors associated with improved HCC surveillance.3–5 Those studies addressed the association of adherence to HCC surveillance programs in cirrhotic patients with patients’ knowledge, attitudes, and perceived barriers mainly through self-reporting surveys.

    Date de mise en ligne : Mardi 09 mai 2017
    Won-Jung Shin, Gyu-Sam Hwang
    Reply to: “Pressure volume curves in cirrhosis: More than meets the eye”
    We would like to thank Dr. Ripoll et al. for their great interest in our paper. They commented that there was an inaccuracy of noninvasive single-beat approach for estimating Ees (end-systolic left ventricular elastance). Although it is already clearly described in the limitation section of our paper, we correspond with their remarks, because a non-invasive method has inherent limitations compared to an invasive approach. However, an invasive method to obtain exact Ees, a slope of end-systolic pressure-volume relation (ESPVR), is surprisingly too invasive, requiring both LV catheters and occlusion balloon obstructing inferior vena cava in humans.

    Date de mise en ligne : Lundi 08 mai 2017
    Alvaro Santos-Laso, María J. Perugorria, Jesús M. Banales
    O-GlcNAcylation: Undesired tripmate but an opportunity for treatment in NAFLD-HCC
    Non-alcoholic liver disease (NAFLD) is acknowledged as the hepatic manifestation of the metabolic syndrome. The prevalence of NAFLD has dramatically increased in the last years due to “globesity” (i.e. the global epidemic of being overweight and obesity) and diabetes.1,2 Although NAFLD is considered a benign condition, it can progress to non-alcoholic steatohepatitis (NASH), which is a major risk factor for the development of hepatocellular carcinoma (HCC).3 Notably, NASH accounts for a significant proportion (13–38%) of cryptogenic HCC cases developed in cirrhotic or non-cirrhotic livers.

    Date de mise en ligne : Lundi 08 mai 2017
    Milan Jirsa
    Cytotoxic bilirubin metabolites overlooked so far
    Whereas the biological properties and toxicity of biliverdin,1 bilirubin2–4 and its photoizomers5 have been studied for decades, to date, the bioactive properties of bilirubin degradation products, resulting mainly from bilirubin oxidation, have been overlooked. The present paper by Seidel and colleagues describing the bioactive properties of two major bilirubin degradation products Z-BOX A and B aims to fill the gap in this field. The study is a natural continuation of the series of three previous papers published in chemical journals that describe the acquisition of the key tools essential for subsequent biological studies: synthesis of Z-BOX A,6 synthesis of Z-BOX B7 and a liquid chromatography – tandem mass spectrometry method suitable for simultaneous determination of both Z-BOXes in biological specimens.

    Date de mise en ligne : Lundi 08 mai 2017
    Cristina Ripoll, Raquel Yotti, Rafael Bañares, Javier Bermejo
    Pressure Volume Curves in Cirrhosis: more than meets the eye
    We read with great interest the study of Shin et al “Effect of ventriculo-arterial coupling on transplant outcomes in cirrhotics: analysis of pressure volume curve relations“ published in the February issue of Journal of Hepatology [1]. In their study, the authors evaluate the prognostic role of non-invasive estimations of cardiac chamber properties based on the pressure volume relationship in a large group of patients with cirrhosis, and conclude that the ventricular-arterial coupling can be used as prognostic index in patients with cirrhosis undergoing liver transplantation.

    Date de mise en ligne : Samedi 06 mai 2017
    Sunyoung Lee, Seong Hyun Kim, Ji Eun Lee, Dong Hyun Sinn, Cheol Keun Park
    Preoperative Gadoxetic acid-enhanced MRI for Predicting Microvascular Invasion in Patients with Single hepatocellular carcinoma
    Vascular invasion, either macrovascular or microvascular invasion (MVI), is a well-known major prognostic factor of hepatocellular carcinoma (HCC) after surgical resection or liver transplantation [1–4]. In particular, MVI of HCC is a major risk factor for early recurrence within the first 2 years after curative treatment [5,6]. Although macrovascular invasion can be frequently detected prior to surgery by complementary imaging modalities including computed tomography (CT) and magnetic resonance (MR) imaging, MVI can rarely be determined preoperatively because it is a histopathological diagnosis.

    Date de mise en ligne : Vendredi 05 mai 2017
    Alfonso Tan-Garcia, Lu-En Wai, Dahai Zheng, Erica Ceccarello, Juandy Jo, Nasirah Banu, Atefeh Khakpoor, Adeline Chia, Christine Y.L. Tham, Anthony T. Tan, Michelle Hong, Choong Tat Keng, Laura Rivino, Kai Chah Tan, Kang Hoe Lee, Seng Gee Lim, Evan W. Newell, Norman Pavelka, Jinmiao Chen, Florent Ginhoux, Qingfeng Chen, Antonio Bertoletti, Charles-Antoine Dutertre
    Intrahepatic CD206+ macrophages contribute to inflammation in advanced viral-related liver disease
    Chronic viral infections (HBV and HCV) are leading causes of end-stage liver disease (cirrhosis or HCC) [1]. Since both viruses are not directly cytopathic, hepatocyte death and related inflammatory events are thought to be principally caused by activated virus-specific T cells recognising infected hepatocytes [2]. However, in chronic viral hepatitis, unlike an acute infection, virus-specific T cells are low in frequency and even undetectable in end-stage liver disease [3]. In addition, virus-specific T cells are often functionally exhausted [4,5].

    Date de mise en ligne : Vendredi 05 mai 2017
    Mitra K. Nadim, Joseph DiNorcia, Lingyun Ji, Susan Groshen, Josh Levitsky, Randall S. Sung, W. Ray Kim, Kenneth Andreoni, David Mulligan, Yuri S. Genyk
    Inequity In Organ Allocation For Patients Awaiting Liver Transplantation: Rationale for Uncapping the Model for End-Stage Liver Disease
    The disparity between the availability of donor organs and the growing number of patients awaiting transplant is one of the greatest challenges in organ transplantation. A needs-based allocation policy prioritizes those at greatest risk of death on the waitlist while a utility-based policy prioritizes graft and patient survival. In 1998, the United States (US) Department of Health and Human Services adopted the Final Rule, which set guidelines for organ allocation based on medical urgency.[1] The goal was to balance equity and utility in the distribution of organs while avoiding futility.

    Date de mise en ligne : Vendredi 05 mai 2017
    Johanne Poisson, Aurélie Plessier, Jean-Jacques Kiladjian, Fanny Turon, Bruno Cassinat, Annalisa Andreoli, Emmanuelle De Raucourt, Odile Goria, Kamal Zekrini, Christophe Bureau, Florence Lorre, Francisco Cervantes, Dolors Colomer, François Durand, Juan-Carlos Garcia-Pagan, Nicole Casadevall, Dominique-Charles Valla, Pierre-Emmanuel Rautou, Christophe Marzac, for the French national network for vascular liver diseases
    Selective testing for calreticulin gene mutations in patients with splanchnic vein thrombosis: A prospective cohort study
    Splanchnic vein thrombosis (SVT) indicates Budd-Chiari syndrome (BCS) and portal venous system thrombosis (PVT). Primary BCS is a rare disorder defined as a blocked hepatic venous outflow tract at various levels from small hepatic veins to the terminal portion of the inferior vena cava [1]. Nonmalignant noncirrhotic extrahepatic PVT is characterized by a thrombus developed in the main portal vein and/or its right or left branches and/or splenic or mesenteric veins, or by the permanent obliteration that results from a prior thrombus [1].

    Date de mise en ligne : Vendredi 05 mai 2017
    Jessica Fioravanti, Pietro Di Lucia, Diletta Magini, Federica Moalli, Carolina Boni, Alexandre Pierre Benechet, Valeria Fumagalli, Donato Inverso, Andrea Vecchi, Amleto Fiocchi, Stefan Wieland, Robert Purcell, Carlo Ferrari, Francis V. Chisari, Luca G. Guidotti, Matteo Iannacone
    Effector CD8+ T cell-derived interleukin-10 enhances acute liver immunopathology
    It is widely recognized that HBV replicates noncytopathically in the hepatocyte and that most of the clinical syndromes related to this infection reflect the adaptive immune response, particularly the virus-specific effector CD8+ T cell response [1–5]. Indeed, by killing infected cells and secreting antiviral cytokines, effector CD8+ T cells (CD8 TE) that have reached infection sites are major contributors to viral clearance as well as tissue immunopathology [1–5]. Paradoxically, during some acute viral infections (e.g.

    Date de mise en ligne : Vendredi 05 mai 2017
    Johannes Mueller, Hanna Raisi, Vanessa Rausch, Teresa Peccerella, David Simons, Christian Ziener, Heinz-Peter Schlemmer, Helmut Karl Seitz, Nina Waldburger, Thomas Longerich, Beate Katharina Straub, Sebastian Mueller
    Sensitive and non-invasive assessment of hepatocellular iron using a novel room-temperature susceptometer
    Besides hereditary iron overload diseases [1,2], many chronic liver diseases ultimately cause hepatic iron overload (HIO) such as HCV, NAFLD and ALD [3]. HIO is highly toxic and cancerogenic in animal models [4,5] due to the Fenton chemistry [6]. In humans, both in hereditary hemochromatosis and ALD, HIO determines the overall survival [7,8] and independently increases the risk of HCC [9,10]. While consequent treatment of HIO e.g. in hemochromatosis or thalassemia efficiently improves survival, the role of phlebotomy or chelation therapy in metabolic and viral liver disease still remains unsettled [3].

    Date de mise en ligne : Vendredi 05 mai 2017
    Giulia Bellini, Emanuele Miraglia del Giudice, Valerio Nobili, Francesca Rossi
    The IRGM rs10065172 variant increases the risk for steatosis but not for liver damage progression in Italian obese children
    We read with great interest the article by Lin et al.1 regarding the ability of the autophagy-related gene (IRGM) variants to confer susceptibility to non-alcoholic fatty liver disease (NAFLD) by modulating lipophagy. Autophagy plays a crucial role in hepatocyte lipid storage. The study firstly demonstrates that IRGM variants increase the risk for NAFLD in obese children. In particular, the IRGM-rs10065172 TT-genotype increases the risk of twice compared to other genotypes regardless of the contribution to NAFLD given by i) genetic factors (PNPLA3, GCKR and TMS6F2 variants), ii) phenotypic factors (insulin resistance and body mass index), and iii) predisposing factors (age and sex).

    Date de mise en ligne : Vendredi 05 mai 2017
    Yu-Cheng Lin, Yen-Hsuan Ni
    Reply to: “Title: The IRGM rs10065172 variant increases the risk for steatosis but not for liver damage progression in Italian obese children”
    To the Editor:

    Date de mise en ligne : Mercredi 03 mai 2017
    Che C. Colpitts, Thomas F. Baumert
    SCARB1 variants and HCV infection: Host susceptibility is lost in translation
    Approximately 150 million people are chronically infected with hepatitis C virus (HCV). Despite the remarkable advancement of direct-acting antiviral agents (DAAs) in recent years, achieving high cure rates, HCV remains a major global health burden. In the absence of curative therapy, chronically infected individuals are at high risk of developing severe liver disease, including cirrhosis and hepatocellular carcinoma (HCC). Even viral cure does not eliminate the risk of HCC in all patients.1 Approximately 25% of HCV-infected individuals spontaneously clear infection in the acute phase and do not go on to become chronically infected.

    Date de mise en ligne : Mardi 02 mai 2017
    Jean-Nicolas Vauthey, Takashi Mizuno, Michael J. Overman, Olivier Soubrane
    Can we navigate chemotherapy-induced hepatic injuries from pathology to bedside?
    In 2004, Rubbia-Brandt reported the association between oxaliplatin-based chemotherapy and sinusoidal dilatation corresponding to sinusoidal obstruction syndrome (SOS).1 Since then, a wide spectrum of chemotherapy-associated liver injuries (CALI) and the clinical importance of the association between CALI and higher postoperative mortality and morbidity, including major and liver-specific complications, have been reported.2–4

    Date de mise en ligne : Vendredi 28 avril 2017
    Angela C. Cheung, Brian D. Juran, Raymond M. Moore, Nicholas F. LaRusso, Konstantinos N. Lazaridis
    Doublecortin domain containing protein 2 (DCDC2) genetic variants in primary sclerosing cholangitis
    We read with great interest the study by T. Grammatikopoulos et al. that reported an association between neonatal sclerosing cholangitis (NSC) and loss of function mutations in doublecortin domain containing protein 2 (DCDC2).1 On electron microscopy, the cholangiocytes of these patients lacked primary cilia.

    Date de mise en ligne : Vendredi 28 avril 2017
    Tassos Grammatikopoulos, Richard J Thompson
    Reply to: “Doublecortin domain containing protein 2 (DCDC2) genetic variants in primary sclerosing cholangitis”
    We would like to thank Cheung et al. for their comments on possible genetic associations between neonatal sclerosing cholangitis (NSC) and primary sclerosing cholangitis (PSC).1 Cheung et al. through whole exome sequencing in a group of 67 (30 under 18years old) patients diagnosed with PSC, identified three missense variants in doublecortin domain containing 2 (DCDC2) gene [c.1368A>T; p.(Lys456Asn), c.661A>G; p.(Ser221Gly) and c.454C>G; p.(Pro152Ala)] with minimal predicted effect on protein function.

    Date de mise en ligne : Vendredi 21 avril 2017
    Dorothea Bankwitz, Mandy Doepke, Kathrin Hueging, Romy Weller, Janina Bruening, Patrick Behrendt, Ji-Young Lee, Florian W.R. Vondran, Michael P. Manns, Ralf Bartenschlager, Thomas Pietschmann
    Maturation of secreted HCV particles by incorporation of secreted apoE protects from antibodies by enhancing infectivity
    Hepatitis C virus (HCV) is a hepatotropic, RNA virus of the family Flaviviridae that is transmitted parenterally [1]. HCV encodes a single polyprotein that is cleaved by cellular and viral enzymes into the structural proteins core and envelope protein 1 (E1) and E2, the p7 ion channel protein, and the non-structural proteins NS2, NS3, NS4A, NS4B, NS5A and NS5B. The capsid protein encases the viral RNA genome and the E1-E2 proteins are embedded into the viral lipid membrane and they mediate receptor interactions and viral membrane fusion during cell entry.

    Date de mise en ligne : Vendredi 21 avril 2017
    Marcel Klingenberg, Akiko Matsuda, Sven Diederichs, Tushar Patel
    Non-coding RNA in hepatocellular carcinoma: Mechanisms, biomarkers and therapeutic targets
    The development of high-throughput RNA sequencing technology has led to the discovery of thousands of ncRNA genes. The number of newly identified ncRNA genes is increasing and already outnumbers the number of coding transcripts [1]. Non-coding RNAs (ncRNAs) are participating in a plethora of physiological and pathological processes [2,3]. This was surprising since most of the ncRNAs were thought to be the product of random transcription without any intrinsic function. But instead of solely being “junk RNA”, there is evidence that ncRNAs are functionally important molecules in the cell [2].

    Date de mise en ligne : Vendredi 21 avril 2017
    Naoki Kawagishi, Goki Suda, Masahiro Onozawa, Megumi Kimura, Osamu Maehara, Jun Ito, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
    Hepatitis B virus reactivation during hepatitis C direct-acting antiviral therapy in patients with previous HBV infection
    The worldwide use of interferon (IFN)-free direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) infection has raised concerns regarding hepatitis B virus (HBV) reactivation after HCV clearance. In patients with HCV and HBV co-infection, HBV-reactivation has been reported during or after IFN-based anti-HCV treatment. Because HCV is thought to suppress HBV replication,1 therapeutic eradication of HCV may increase HBV replication, resulting in HBV-reactivation. Until recently, the standard therapy for chronic HCV infection was IFN-based therapy.

    Date de mise en ligne : Jeudi 20 avril 2017
    Anderson Brito-Azevedo
    Carvedilol and survival in cirrhosis with ascites: A cognitive bias?
    I read with great interest the study performed by Sinha and co-workers. They examined whether long-term use of carvedilol in the presence of ascites is a risk factor for mortality.1

    Date de mise en ligne : Jeudi 20 avril 2017
    Sofie Hallager, Steen Ladelund, Nina Weis
    Methodological considerations when calculating person-time at risk for patients with chronic hepatitis C undergoing antiviral treatment
    We have read the manuscript entitled “Survival of patients with HCV cirrhosis and sustained virologic response is similar to the general population” by Bruno et al. published in Journal of Hepatology with great interest.1 The authors show that overall survival among chronic hepatitis C (CHC) patients with compensated cirrhosis after the achievement of sustained virologic response 24weeks after end of treatment (SVR24) is similar to survival observed in the sex- and age-matched background population in Italy (standardized mortality ratio 1.00 (95% confidence interval 0.72–1.35)).

    Date de mise en ligne : Jeudi 20 avril 2017
    Rohit Sinha, Khalida A. Lockman, John N. Plevris, Peter C. Hayes
    Reply to: “Carvedilol and survival in cirrhosis with ascites: A cognitive bias?”
    We acknowledge the letter from Dr Brito-Azevedo in response to our paper, “Carvedilol use is associated with improved survival in patients with liver cirrhosis and ascites”.1 We do not accept the idea of cognitive bias in our study; instead, we put forward the argument of cognitive ability based on our extensive clinical experience.2 Our study was designed to address the anxiety around using beta-blockers in patients with advanced liver disease, which led to the ‘window hypothesis’.3,4

    Date de mise en ligne : Jeudi 20 avril 2017
    Savino Bruno, Patrick Maisonneuve
    Reply to: “Methodological considerations when calculating person-time at risk for patients with chronic hepatitis C undergoing antiviral treatment”
    In response to the letter from Dr. Hallager,1 we previously show that patients with compensated hepatitis C virus (HCV) cirrhosis achieving a sustained virologic response (SVR) by interferon-based (IFN) regimen obtain a main benefit of leveling their survival curve to that of the general population.2 However, we started follow-up of patients with SVR from the date of initiation of antiviral therapy. We agree with Dr. Hallager that this may have introduced an immortal time bias since response to IFN was determined only 24weeks after the treatment cessation.

    Date de mise en ligne : Jeudi 20 avril 2017
    Jordi Colmenero, Pau Sancho-Bru
    Mesenchymal stromal cells for immunomodulatory cell therapy in liver transplantation: One step at a time
    Infusion of mesenchymal stromal cells (MSCs) for the treatment of liver injury and disease has shown promising results in preclinical studies, with reports of a wide variety of MSC action. MSCs are cells of mesenchymal origin, which are defined by three main criteria: adhesion to plastic, expression of particular immunophenotypic markers and their capacity to differentiate into mesodermal cell lineages, such as adipocytes, chondrocytes or osteocytes.1 Although under in vitro conditions MSCs can be induced to acquire features of liver cells such as hepatocytes, bona fide differentiation to endodermal cells has not been sufficiently proven, and their differentiation towards non-mesodermal lineages is debated.

    Date de mise en ligne : Lundi 17 avril 2017
    European Association for the Study of the Liver
    EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis
    Primary biliary cholangitis (PBC) is a chronic inflammatory autoimmune cholestatic liver disease, which when untreated will culminate in end-stage biliary cirrhosis. Diagnosis is usually based on the presence of serum liver tests indicative of a cholestatic hepatitis in association with circulating antimitochondrial antibodies. Patient presentation and course can be diverse and risk stratification is important to ensure all patients receive a personalised approach to their care. The goals of treatment and management are the prevention of end-stage liver disease, and the amelioration of associated symptoms.

    Date de mise en ligne : Lundi 17 avril 2017
    European Association for the Study of the Liver
    EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection
    Hepatitis B virus (HBV) infection remains a global public health problem with changing epidemiology due to several factors including vaccination policies and migration. This Clinical Practice Guideline presents updated recommendations for the optimal management of HBV infection. Chronic HBV infection can be classified into five phases: (I) HBeAg-positive chronic infection, (II) HBeAg-positive chronic hepatitis, (III) HBeAg-negative chronic infection, (IV) HBeAg-negative chronic hepatitis and (V) HBsAg-negative phase.

    Date de mise en ligne : Lundi 17 avril 2017
    European Society of Gastrointestinal Endoscopy, European Association for the Study of the Liver
    Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline
    This guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE) and of the European Association for the Study of the Liver (EASL) on the role of endoscopy in primary sclerosing cholangitis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence.Main recommendations

    Date de mise en ligne : Jeudi 13 avril 2017
    Christine Thöns, Tina Senff, Theresa J. Hydes, Angela R. Manser, Falko M. Heinemann, Andreas Heinold, Martin Heilmann, Arthur Y. Kim, Markus Uhrberg, Norbert Scherbaum, Georg M. Lauer, Salim I. Khakoo, Jörg Timm
    HLA-Bw4 80(T) and multiple HLA-Bw4 copies combined with KIR3DL1 associate with spontaneous clearance of HCV infection in people who inject drugs
    After exposure to HCV the majority of PWID develop chronic HCV infection that can lead to liver cirrhosis and hepatocellular carcinoma. A small subgroup of PWID is able to clear HCV infection before and after seroconversion. PWID with multiple Bw4 alleles are more likely to clear HCV prior to seroconversion than PWID with one or no Bw4 allele. In addition PWID that encode both KIR3DL1 and a Bw4 80(T) motif have higher chances of spontaneously clearing HCV after seroconversion.

    Date de mise en ligne : Jeudi 13 avril 2017
    Daniela Lenggenhager, Jérôme Gouttenoire, Mohsen Malehmir, Marion Bawohl, Hanna Honcharova-Biletska, Susanne Kreutzer, David Semela, Jörg Neuweiler, Sandra Hürlimann, Patrick Aepli, Montserrat Fraga, Roland Sahli, Luigi Terracciano, Laura Rubbia-Brandt, Beat Müllhaupt, Christine Sempoux, Darius Moradpour, Achim Weber
    Visualization of hepatitis E virus RNA and proteins in the human liver
    Hepatitis E virus (HEV) is a non-enveloped, positive-strand RNA virus of the family Hepeviridae and genus Orthohepevirus.1 It is a water- or food-borne, enterically transmitted infectious agent, causing the most common form of acute viral hepatitis worldwide, thus constituting a globally significant health problem.2,3 The 7.2kb HEV genome comprises three opening reading frames (ORF) coding for the viral replicase (ORF1), the capsid protein (ORF2), and a small phosphoprotein required for the secretion of viral particles (ORF3), respectively.

    Date de mise en ligne : Jeudi 13 avril 2017
    Paul Y. Kwo, Fred Poordad, Armen Asatryan, Stanley Wang, David L. Wyles, Tarek Hassanein, Franco Felizarta, Mark S. Sulkowski, Edward Gane, Benedict Maliakkal, J. Scott Overcash, Stuart C. Gordon, Andrew J. Muir, Humberto Aguilar, Kosh Agarwal, Gregory J. Dore, Chih-Wei Lin, Ran Liu, Sandra S. Lovell, Teresa I. Ng, Jens Kort, Federico J. Mensa
    Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1–6 without cirrhosis
    Hepatitis C virus (HCV) infection is a global disease burden, with 350,000 deaths attributed to HCV-related complications annually.1,2 Geographic distributions of HCV genotypes vary widely.2,3 Of the six major HCV genotypes, genotype 3 infection accounts for approximately 30% of global HCV infections and is now considered the most difficult to cure with interferon (IFN)-free direct-acting antiviral (DAA) therapy.3,4 Highly effective and safe IFN-free DAA HCV treatments are available, and some may provide broad coverage for all six major genotypes with 12 weeks of treatment.

    Date de mise en ligne : Jeudi 13 avril 2017
    Alexandre Louvet, Markus Peck-Radosavljevic
    Evidence for a role of genetics in alcoholic hepatitis: Data from the STOPAH randomized controlled trial
    Severe alcoholic hepatitis occurs in heavy drinkers and is associated with a poor outcome. It is assumed that about 40% of patients will not survive 6months after the acute insult.1 Corticosteroids are the best documented treatment for severe alcoholic hepatitis, based on randomized controlled trials and metaanalyses.2–5 More recently, the STOPAH trial,6 based on a factorial design, has shown that pentoxifylline was inefficient, whereas prednisolone had a positive, although limited, effect on short-term (28-day) survival, which was the primary endpoint.

    Date de mise en ligne : Jeudi 13 avril 2017
    Daniela Katinka van Santen, Jannie Johanna van der Helm, Julia Del Amo, Laurence Meyer, Antonella D'Arminio Monforte, Matt Price, Charles Antoine Béguelin, Robert Zangerle, Mette Sannes, Kholoud Porter, Ronald Bertus Geskus, Maria Prins, CASCADE Collaboration in EuroCoord
    Lack of decline in hepatitis C virus incidence among HIV-positive men who have sex with men during 1990–2014
    Since 2000, hepatitis C virus (HCV) incidence has increased among HIV-positive men who have sex with men (MSM).1,2 Using data from the CASCADE Collaboration (Concerted Action on SeroConversion to AIDS and Death in Europe) in EuroCoord, we previously showed that HCV incidence increased in MSM with well-estimated HIV seroconversion dates after 1990, but the main expansion of the HCV epidemic was observed from 2002 until 2007, the censoring date of the analysis.1 A recent meta-analysis showed that HCV incidence has continued to increase, with an estimated pooled incidence of 13/1,000 person-years (py) in 2010 to an extrapolated incidence estimate of 19/1,000 py in 2015.

    Date de mise en ligne : Jeudi 13 avril 2017
    Raphael A. Seidel, Thierry Claudel, Franziska A. Schleser, Navin K. Ojha, Matthias Westerhausen, Sandor Nietzsche, Christoph Sponholz, Frans Cuperus, Sina M. Coldewey, Stefan H. Heinemann, Georg Pohnert, Michael Trauner, Michael Bauer
    Impact of higher-order heme degradation products on hepatic function and hemodynamics
    Heme (iron protoporphyrin IX) serves as a prosthetic group in a variety of proteins involved in oxygen transport, redox reactions, and signaling.1 When released extracellularly, labile heme acts as an alarmin2 and cytotoxic agonist3 that is encountered by scavenger systems.4 Intracellular heme concentrations are tightly controlled by its enzymatic degradation via heme oxygenases (HO),5 yielding the first-order degradation products biliverdin, ferrous iron, and carbon monoxide (CO).6,7 The induction of HO-1 reflects a hallmark of the cellular response to oxidative stress and confers tissue protection during infection and inflammation.

    Date de mise en ligne : Jeudi 13 avril 2017
    Ruth Zimmermann, Christian Kollan, Patrick Ingiliz, Stefan Mauss, Daniel Schmidt, Viviane Bremer
    Reply to “Negotiating better discounts for DAA therapy is critical to achieve HCV elimination by 2030”
    We thank Dr. Dore and Dr. Grebely for their interest in our study. In their letter, the authors compare the response concerning the availability of direct acting antivirals (DAAs) of the Australian healthcare system with the German situation, as published by us. The conclusion is that the tenfold higher costs in Germany may lead to an indirect prioritization of patients, and therefore negatively impact access to therapy. We agree that the tenfold disparity in DAA drug pricing between two high income countries is irritating and probably has a negative impact on the steps towards a global elimination of hepatitis C.

    Date de mise en ligne : Mardi 11 avril 2017
    Nicola Tumino, Rita Casetti, Gabriele Fabbri, Eleonora Cimini, Antonella Romanelli, Federica Turchi, Olindo Forini, Veronica Bordoni, Andrea Antinori, Adriana Ammassari, Alessandra Sacchi, Chiara Agrati
    In HIV/HCV co-infected patients T regulatory and myeloid-derived suppressor cells persist after successful treatment with directly acting antivirals
    The advent of directly acting antivirals (DAA) has revolutionized hepatitis C virus (HCV) treatment, also in patients with HIV co-infection.1 DAA are able to quickly clear HCV with a high success rate because of their potent antiviral action, resulting in more than 90% of sustained virological response (SVR). Although this is an extraordinary improvement in virological efficacy, several issues concerning the medium and long-term response remain to be addressed: regression of hepatic fibrosis, reduction of liver cancer incidence, and normalization of immunological functions.

    Date de mise en ligne : Mardi 11 avril 2017
    Gregory J. Dore, Jason Grebely
    Negotiating better discounts for DAA therapy is critical to achieve HCV elimination by 2030
    The paper from Zimmerman et al. estimating the number of people treated and total costs of direct-acting antiviral (DAA) therapy in Germany between 2010 and 20151 brings into focus major disparities in drug pricing globally, and the impact this may have in achieving HCV elimination goals.

    Date de mise en ligne : Mardi 11 avril 2017
    Hamid Hasson, Marco Merli, Emanuela Messina, Sherrie Bhoori, Stefania Salpietro, Giulia Morsica, Enrico Regalia, Sabrina Bagaglio, Adriano Lazzarin, Caterina Uberti-Foppa, Vincenzo Mazzaferro
    Occurrence of hepatocellular carcinoma in HIV/HCV co-infected patients treated with direct-acting antivirals
    We read with great interest the manuscripts by Conti et al. and Cheung et al. on the incidence of de novo hepatocellular carcinoma (HCC) in patients with liver cirrhosis treated with interferon-free anti-HCV direct-acting antivirals (DAAs)-based regimens.1,2 Their papers followed a “note of caution” related to an unexpected high incidence of recurring HCC after resection or ablation while on DAAs-based therapy,3 and this triggered a controversial debate with potential clinical implications.4

    Date de mise en ligne : Dimanche 09 avril 2017
    Bettina Langhans, Ulrich Spengler
    Reply to “In HIV/HCV co-infected patients T regulatory and myeloid derived suppressor cells persist after successful treatment with directly acting antivirals”
    DAAs in hepatitis C – do they reverse all?

    Date de mise en ligne : Vendredi 07 avril 2017
    Michaël Schwarzinger, Sylvain Baillot, Yazdan Yazdanpanah, Jürgen Rehm, Vincent Mallet
    Contribution of alcohol use disorders on the burden of chronic hepatitis C in France, 2008–2013: A nationwide retrospective cohort study
    Since its discovery in 1989, the hepatitis C virus (HCV) has been recognized as a major cause of liver disease progression to liver-related complications and mortality worldwide.1 New direct-acting antiviral drug combinations showing up to 100% efficacy to eradicate HCV were marketed in early 2014.2 Liver disease progression models support widespread screening and treatment to reduce the burden of HCV.3 The underlying assumptions of these models are usually twofold: 1) chronic HCV infection is the main factor of liver disease progression; 2) cured patients revert to the risks of liver-related complications and mortality of the general population.

    Date de mise en ligne : Jeudi 06 avril 2017
    Deepak Agrawal, Brian Davis, Andrew Quinn, Dwain Thiele
    Should anti-LKM1 be routine for work-up of elevated liver enzymes?
    We read with interest the simulation model approach by Tapper et al. to answer an important and practical question of non-directed (testing for all diseases at once) vs. directed (just common diseases first) testing of patients with elevated liver enzymes.1 The authors conclude that the testing for elevated liver enzymes should be deliberate and directed to account for pre-test probabilities (i.e. testing for rare diseases should be performed only after common diseases are excluded).

    Date de mise en ligne : Jeudi 06 avril 2017
    Elliot B. Tapper, Neil Sengupta
    Reply to: “Should anti-LKM1 be routine for work-up of elevated liver enzymes?”
    The diagnostic evaluation of elevated liver enzymes is an exceedingly common clinical activity. Dozens of serologic tests are available for this purpose, each easily selected with the convenience of a click in most electronic health records. We recently studied a cost-utility model of directed vs. extensive testing based on the two available population-based studies of elevated liver enzymes.1 In aggregate these studies – both the model and the primary data on which it was based2,3 – reinforce that the vast majority of patients have non-alcoholic fatty liver disease or alcoholic liver disease, both of which lack serologic tests for diagnosis.

    Date de mise en ligne : Jeudi 06 avril 2017
    Elham Shirvani-Dastgerdi, Benjamin Y. Winer, Toni Celià-Terrassa, Yibin Kang, David Tabernero, Eray Yagmur, Francisco Rodríguez-Frías, Josep Gregori, Tom Luedde, Christian Trautwein, Alexander Ploss, Frank Tacke
    Selection of the highly replicative and partially multidrug resistant rtS78T HBV polymerase mutation during TDF-ETV combination therapy
    Over 240 million people are chronically infected with the hepatitis B virus (HBV) worldwide. Despite advances in vaccination and treatment, HBV-related deaths due to liver cirrhosis or hepatocellular carcinoma (HCC) increased between 1990 and 2013 globally by 33% to >686,000 cases in 2013.1 Therefore, the main treatment goal for chronic hepatitis B is to suppress viral replication and consequently to prevent progression of the disease.2 In most cases, this is achieved by the orally available nucleos(t)ide analogues that act as competitive inhibitors of the HBV reverse transcriptase, as their incorporation into the DNA strand provokes chain termination and hence suppresses HBV replication.

    Date de mise en ligne : Mardi 04 avril 2017
    Sumera Rizvi, Gregory J. Gores
    Emerging Molecular Therapeutic Targets for Cholangiocarcinoma
    Cholangiocarcinomas (CCAs) are diverse epithelial tumors arising from the liver or large bile ducts with features of cholangiocyte differentiation, and are classified anatomically into intrahepatic (iCCA), perihilar (pCCA), and distal CCA (dCCA). Each subtype has distinct risk factors, molecular pathogenesis, therapeutic options, and prognosis. CCA is an aggressive malignancy with a poor overall prognosis and median survival of less than 2 years in patients with advanced disease. Potentially curative surgical treatment options are limited to the subset of patients with early stage disease.

    Date de mise en ligne : Vendredi 31 mars 2017
    Toshifumi Tada, Takashi Kumada, Hidenori Toyoda
    Reply to: “HBV markers for HCC prediction: Three heads are better than two?”
    Thank you for your interest in our article “HBcrAg predicts hepatocellular carcinoma development: An analysis using time-dependent receiver operating characteristics”.1 In this study, we showed that the elevation of hepatitis B virus (HBV) core-related antigen (HBcrAg) was associated with the development of hepatocellular carcinoma (HCC) in 1,031 Japanese chronic hepatitis B (CHB) patients who were not treated with nucleos(t)ide analogue therapy. The main purpose of this study was to clarify the predictive power of HBV markers for the development of HCC using receiver operating characteristic curve analysis with a consideration for time dependence, rather than simply using univariate and multivariate analyses of hepatocarcinogenesis.

    Date de mise en ligne : Vendredi 31 mars 2017
    Tai-Chung Tseng, Jia-Horng Kao
    HBV markers for HCC prediction: Three heads are better than two?
    We read with great interest the article entitled “HBcrAg predicts hepatocellular carcinoma development: An analysis using time-dependent receiver operating characteristics” by Tada et al. published in July 2016.1

    Date de mise en ligne : Mercredi 29 mars 2017
    Ji Yeon Kim, Keon Jae Park, Joo-Yeon Hwang, Gyu Hee Kim, DaeYeon Lee, Yoo Jeong Lee, Eun Hyun Song, Min-Gyu Yoo, Bong-Jo Kim, Young Ho Suh, Gu Seob Roh, Bin Gao, Won Kim, Won-Ho Kim
    Activating transcription factor 3 is a target molecule linking hepatic steatosis to impaired glucose homeostasis
    Obesity is a major underlying risk factor for type 2 diabetes (T2D).1 A common pathogenic event in both animals and humans with obesity and T2D is hepatic lipid accumulation, which is the earliest phenotype of non-alcoholic fatty liver disease (NAFLD).2 NAFLD has reached epidemic levels worldwide because its incidence has gradually increased in the non-obese Asian population as well as the obese populations of the United States and Europe.3 Non-alcoholic steatohepatitis (NASH) is the histologic form of NAFLD that is associated with increased morbidity and mortality, and it is closely linked to hepatic insulin resistance and abnormal glucose metabolism.

    Date de mise en ligne : Mardi 28 mars 2017
    Sandra Westhaus, Maximilian Deest, Anna T.X. Nguyen, Frauke Stanke, Dirk Heckl, Rui Costa, Axel Schambach, Michael P. Manns, Thomas Berg, Florian W.R. Vondran, Christoph Sarrazin, Sandra Ciesek, Thomas von Hahn
    Scavenger receptor class B member 1 (SCARB1) variants modulate hepatitis C virus replication cycle and viral load
    Today about 2% of the world population are chronically infected with the hepatitis C virus (HCV). Unless detected in time and treated successfully, chronic hepatitis C often leads to cirrhosis, hepatocellular carcinoma and the need for liver transplantation. Recently approved novel specific antiviral drugs have markedly increased the chances of curing infection. Nonetheless HCV infection remains a significant public health challenge and one of the main reasons for liver transplantation.1 Moreover, many aspects in the molecular interaction between this major pathogen and its human host remain to be fully understood.

    Date de mise en ligne : Vendredi 24 mars 2017
    Mamatha Bhat, Peter Ghali, Marc Bilodeau
    Reply to: “Proposal of a novel MELD exception point system for hepatocellular carcinoma: Dynamics better than tumor characteristics?”
    We thank Lai et al. for their interest in our study, and for their constructive comments regarding the hepatocellular carcinoma (HCC) allocation system we have proposed [1]. We appreciate their reference to the applicability of our system to the European context. Their comments certainly demonstrate that there is a need to refine the current allocation policies, to better reflect tumor biology and dynamics.

    Date de mise en ligne : Vendredi 24 mars 2017
    Jonel Trebicka, Lise Lotte Gluud
    Reply to “Adding embolization to TIPS implantation: A better therapy to control bleeding from ectopic varices?”
    We would like to thank the Perricone and colleagues for their letter and for the interest in the article “Emergency TIPS in a Child-Pugh B patient: When does the window of opportunity open and close?”.1 The letter raises an important question, namely the management of bleeding from ectopic varices. Bleeding from ectopic varices other than fundic varices represents a rare and challenging complication. Guidance for clinical practice is needed.

    Date de mise en ligne : Vendredi 24 mars 2017
    Weiqi Xu, Xiang Zhang, Jian-lin Wu, Li Fu, Ken Liu, Dabin Liu, George Gong Chen, Paul Bo-san Lai, Nathalie Wong, Jun Yu
    O-GlcNAc transferase promotes fatty liver-associated liver cancer through inducing palmitic acid and activating endoplasmic reticulum stress
    Hepatocellular carcinoma (HCC) is one of the most common human malignancies and the third leading cause of cancer death worldwide.1 A retrospective cohort study of indications for adult liver transplantation from 2002 to 2012 revealed a nearly 4-fold increase in patients undergoing liver transplantation for HCC secondary to non-alcoholic steatohepatitis (NASH) compared to only a 2.5-fold increase for HCC secondary to HCV during the study period.2 With the control of viral hepatitis and the escalating obesity epidemic, non-alcoholic fatty liver disease (NAFLD) associated HCC is occupying a greater proportion of HCC incidence in recent decades.

    Date de mise en ligne : Vendredi 24 mars 2017
    Quirino Lai, Massimo Rossi, Jan Lerut
    Proposal of a novel MELD exception point system for hepatocellular carcinoma: Dynamics better than tumor characteristics?
    We read with great interest the paper published by Bhat et al., focusing on the proposal of a new model for end-stage liver disease (MELD) exception point system for hepatocellular cancer (HCC) patients waiting for liver transplantation (LT) [1]. The authors must be congratulated for their very interesting results. In view of the potential application of this model also in a European setting, we noted that 76% of the entire HCC population was treated with any type of loco-regional treatment (LRT) and that the median waiting time (WT) was 8.6months.

    Date de mise en ligne : Vendredi 24 mars 2017
    Giovanni Perricone, Marcello Vangeli, Stella De Nicola, Aldo Airoldi, Luca Saverio Belli
    Adding embolization to TIPS implantation: A better therapy to control bleeding from ectopic varices?
    We read with great interest “Emergency TIPS in a Child-Pugh B patient: When does the window of opportunity open and close?” by Trebicka1. It provides an exhaustive revision of the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of complications of cirrhotic portal hypertension and discusses several frequently debated questions.

    Date de mise en ligne : Jeudi 23 mars 2017
    Tania M. Welzel, Neeru Bhardwaj, Charlotte Hedskog, Krishna Chodavarapu, Gregory Camus, John McNally, Diana Brainard, Michael D. Miller, Hongmei Mo, Evguenia Svarovskaia, Ira Jacobson, Stefan Zeuzem, Kosh Agarwal
    Global epidemiology of HCV subtypes and resistance-associated substitutions evaluated by sequencing-based subtype analyses
    Hepatitis C virus (HCV) is a major human liver pathogen. It is estimated that >170million people are affected worldwide and at risk for progressive liver disease and hepatocellular carcinoma.1,2 HCV is classified into seven genotypes and 67 subtypes, and displays ∼30% divergence at the genotype level and ∼15% divergence at the subtype level.3 HCV diversity is derived in part from its RNA-dependent RNA polymerase (RdRp) that lacks proofreading capability, recombination, genetic drift, and immune pressures on the virus.

    Date de mise en ligne : Mardi 21 mars 2017
    Morgan E. Preziosi, Sucha Singh, Erika V. Valore, Grace Jung, Branimir Popovic, Minakshi Poddar, Shanmugam Nagarajan, Tomas Ganz, Satdarshan P. Monga
    Mice lacking liver-specific β-catenin develop steatohepatitis and fibrosis after iron overload
    Hereditary hemochromatosis, a prototypical iron overload disorder, is one of the most common genetic disorders in the United States. It occurs in approximately 1 in 200 Caucasians, and 40% of the healthy population in the US carry a mutation predisposing them to iron overload.1 Mutations in key iron homeostasis genes cause a progressive accumulation of iron in parenchymal cells of various tissues. The liver is one of the major organs affected, and around 75% of clinically affected hemochromatosis patients have evidence of liver disease at presentation.

    Date de mise en ligne : Lundi 20 mars 2017
    Paola Bertuccio, Federica Turati, Greta Carioli, Teresa Rodriguez, Carlo La Vecchia, Matteo Malvezzi, Eva Negri
    Global trends and predictions in hepatocellular carcinoma mortality
    Primary liver cancer, and specifically hepatocellular carcinoma (HCC), is still the third cause of cancer death worldwide, with exceedingly high rates in East/Southeast Asia, several areas of Africa and, historically, southern Europe. In addition, over the last decade, liver cancer was one of the few cancer sites showing upward trends in both sexes in several countries worldwide.1

    Date de mise en ligne : Samedi 18 mars 2017
    Thomas Jacob Urban, Paola Nicoletti, Naga Chalasani, José Serrano, Andrew Stolz, Ann K. Daly, Guruprasad P. Aithal, John Dillon, Victor Navarro, Joseph Odin, Huiman Barnhart, David Ostrov, Nanye Long, Elizabeth Trilby Cirulli, Paul Brent Watkins, Robert John Fontana, Drug-Induced Liver Injury Network (DILIN), Pharmacogenetics of Drug-Induced Liver Injury group (DILIGEN), International Serious Adverse Events Consortium (iSAEC)
    Minocycline hepatotoxicity: Clinical characterization and identification of HLA-B∗35:02 as a risk factor
    Idiosyncratic drug-induced liver injury (DILI) is an important cause of acute and chronic liver injury in Western patients. In addition to being a leading reason for regulatory actions among drugs in development and in the marketplace, DILI also accounts for 13% of adults with acute liver failure.1 A recent population based study indicated that the annual incidence of DILI was 19.1 per 100,000 person years in Iceland and that antibiotics were the most commonly implicated agents.2 Similarly, analyses from the ongoing Drug-induced Liver Injury Network (DILIN) prospective study in the United States also identified antibiotics as the leading cause of DILI, with amoxicillin-clavulanate being most frequently implicated.

    Date de mise en ligne : Samedi 18 mars 2017
    Sílvia Vilarinho, E. Zeynep Erson-Omay, Kisha Mitchell-Richards, Charles Cha, Carol Nelson-Williams, Akdes Serin Harmancı, Katsuhito Yasuno, Murat Günel, Tamar H. Taddei
    Exome analysis of the evolutionary path of hepatocellular adenoma-carcinoma transition, vascular invasion and brain dissemination
    Hepatocellular adenoma (HCA) is a rare benign liver tumor, predominantly seen in young women. Its major complications are malignant transformation, spontaneous hemorrhage, and rupture. We describe a case of a young female with no underlying liver disease who presented with acute abdominal pain and was found to have a 17cm heterogeneous mass in the left lobe of the liver. She underwent left hepatectomy and pathology revealed a 14cm moderately differentiated hepatocellular carcinoma (HCC) arising in a shell of a HCA.

    Date de mise en ligne : Samedi 18 mars 2017
    Natasha K. Martin, Peter Vickerman, Matthew Hickman
    How to eliminate HCV infection by antiviral treatment
    The advent of new hepatitis C virus (HCV) treatments (direct-acting antivirals, DAAs) with>90% sustained viral response (SVR) rates in 8 to 12weeks has ushered in an era of excitement about the possibility of eliminating HCV transmission. Tantalizing theoretical mathematical models predicting dramatic reductions in HCV chronic prevalence and incidence, with scale-up of HCV treatment for those at risk of transmission, have fueled this optimism.1 Recent reports of a substantial reduction in HCV incidence (∼50% in 2years) among HIV-infected men who have sex with men in the Netherlands after the roll-out of DAA therapy2 has provided the first piece of empirical evidence that HCV treatment as a prevention may be more than just a theoretical idea.

    Date de mise en ligne : Samedi 18 mars 2017
    Peter R. Galle, Francesco Tovoli, Friedrich Foerster, Marcus A. Wörns, Alessandro Cucchetti, Luigi Bolondi
    The treatment of intermediate stage tumours beyond TACE: From surgery to systemic therapy
    Treatment of hepatocellular carcinoma (HCC) is dependent on the stage of the disease. Intermediate stage HCC encompasses the largest subgroup of patients with the disease, and is characterized by substantial heterogeneity. The standard therapeutic approach, transarterial chemoembolization (TACE), is probably over-used and may not be appropriate for all patients with intermediate stage HCC. In patients with extensive tumour bulk, multi-nodular spread or impaired liver function, TACE may not be optimal and other treatments can be considered as a first-line treatment.

    Date de mise en ligne : Samedi 18 mars 2017
    Luca S Belli, Christophe Duvoux, Thomas Berg, Mario Strazzabosco, Stefano Fagiuoli, Saye Khoo, Georges Philippe Pageaux, Isabelle Colle, Massimo Puoti, Audrey Coilly, Didier Samuel, Marina Berenguer, ELITA board members
    ELITA consensus statements on use of DAAs in liver transplant candidates and recipients
    The advent of safe and highly effective direct acting antivirals (DAA) had huge implications for the HCV transplant field and changed our management of both, patients on the waiting list and those with HCV graft reinfection after Liver Transplantation (LT). When treating HCV infection before LT, HCV reinfection of the graft may be prevented in nearly all patients. In addition some candidates show a remarkable clinical improvement and are possibly delisted.Alternatively, HCV infection can be treated post LT either soon after the transplant, taking advantage of the removal of the infected native liver, or at the time of disease recurrence as done in the past.

    Date de mise en ligne : Samedi 18 mars 2017
    Ao Huang, Xin Zhao, Xin-Rong Yang, Fu-Qiang Li, Xin-Lan Zhou, Kui Wu, Xin Zhang, Qi-Man Sun, Ya Cao, Hong-Mei Zhu, Xiang-Dong Wang, Huan-Ming Yang, Jian Wang, Zhao-You Tang, Yong Hou, Jia Fan, Jian Zhou
    Circumventing intratumoral heterogeneity to identify potential therapeutic targets in hepatocellular carcinoma
    Identifying mutations through next generation sequencing facilitates targeted therapy.1 This has led to basket and umbrella trials that have evaluated the use of off-label agents in cancer patients who carry targetable mutations.2 A minority of patients with hepatocellular carcinoma (HCC), who are diagnosed at early stage, can receive curative treatments. For patients with advanced HCC, the standard therapy of sorafenib has a low response rate.3 Therefore, the aim of this study was to explore whether genomic profiling could help select HCC patients who could benefit from sorafenib, or alternatively identify patients who harbor mutations indicating the use of other off-label targeted drugs.

    Date de mise en ligne : Samedi 18 mars 2017
    Stéphanie Patouraux, Déborah Rousseau, Stéphanie Bonnafous, Cynthia Lebeaupin, Carmelo Luci, Clémence M. Canivet, Anne-Sophie Schneck, Adeline Bertola, Marie-Christine Saint-Paul, Antonio Iannelli, Jean Gugenheim, Rodolphe Anty, Albert Tran, Béatrice Bailly-Maitre, Philippe Gual
    CD44 is a key player in non-alcoholic steatohepatitis
    Global prevalence of non-alcoholic fatty liver diseases (NAFLD) ranges from 22% to 28%.1 The spectrum of these hepatic abnormalities extends from isolated steatosis to steatohepatitis (non-alcoholic steatohepatitis, NASH) and steatofibrosis leading to cirrhosis and hepatocellular carcinoma. NAFLD is one of the main causes of cirrhosis and increases the risk of liver-related death and hepatocellular carcinoma. Despite this major public health concern, treatment of NAFLD is still elusive (apart from lifestyle changes) as there is lack of efficacious pharmacological treatment.

    Date de mise en ligne : Mercredi 15 mars 2017
    Robert Montal, Riccardo Lencioni, Josep M. Llovet
    Reply to: mRECIST for systemic therapies: More evidence is required before recommendations could be made
    We appreciate the interest generated by our manuscript, and thank the letter by Dr. Edeline et al. [1] and the Editor for the opportunity of responding.

    Date de mise en ligne : Mercredi 15 mars 2017
    Maurizia Brunetto, Markus Cornberg, Henry Lik-Yuen Chan
    Reply to: Serum HBsAg kinetics in clinical prediction
    We agree with W-J Jeng and Y-F Liaw on the pivotal role of spontaneous hepatitis B surface antigen (HBsAg) serum clearance in the clinical history of a hepatitis B virus (HBV) carrier [1] as it is, the hallmark of the control of HBV replication and transition from inactive to occult infection [2]. However, the reported annual rates of HBsAg clearance are highly variable (0.31 to 3.2×100persons/years) because of the heterogeneity of the studied populations [3–6]: mode of infection, age and ethnicity are major factors influencing the HBsAg loss [5–8].

    Date de mise en ligne : Mercredi 15 mars 2017
    Julien Edeline, Daniel Palmer, Jean-Frédéric Blanc, Boris Campillo-Gimenez, Philippe Merle, Tim Meyer
    mRECIST for systemic therapies: More evidence is required before recommendations can be made
    We read we great interest the article by Lencioni et al. entitled “Objective response by mRECIST as a predictor and potential surrogate endpoint of overall survival in advanced HCC” [1].

    Date de mise en ligne : Mercredi 15 mars 2017
    Wen-Juei Jeng, Yun-Fan Liaw
    Serum HBsAg kinetics in clinical prediction
    We read with great interest the review article “The role of quantitative hepatitis B surface antigen revisited” by Cornberg et al. in the Journal of Hepatology [1]. Indeed, it is a comprehensive update. However, the role of hepatitis B surface antigen (HBsAg) quantification in the prediction of spontaneous or antiviral therapy related HBsAg seroclearance and relapse after cessation of nucleos(t)ide analog (NUC) therapy was not well addressed. The studies mentioned in the review used an HBsAg level <100IU/ml as a predictor for remote (6–10years) HBsAg seroclearance but two studies on short-term prediction of HBsAg seroclearance within 1–3years were not mentioned.

    Date de mise en ligne : Lundi 13 mars 2017
    Wei-Tien Tai, Ann-Lii Cheng, Chung-Wai Shiau, Hsiang-Po Huang, Jui-Wen Huang, Pei-Jer Chen, Kuen-Feng Chen
    Erratum to: Corrigendum to “Signal transducer and activator of transcription 3 is a major kinase-independent target of sorafenib in hepatocellular carcinoma”
    Unfortunately, when correcting the figures on behalf of the authors, a mistake was introduced in Fig.4E by the editorial office. The correct version of Fig.4 can be found below.

    Date de mise en ligne : Mercredi 08 mars 2017
    Jordi Bruix, Maria Reig, Bruno Sangro
    Assessment of treatment efficacy in hepatocellular carcinoma: Response rate, delay in progression or none of them
    Assessing the response to treatment is a critical aspect in the management of patients with hepatocellular carcinoma (HCC), as is the case in all cancer types [1–3]. The aim of treatment is to induce a change in the evolution of the tumor, so that it translates into an improvement of patient survival. Since growth and dissemination are the hallmarks of cancer leading to death, any intervention that reduces tumor burden or delays such events is commonly considered to provide a survival benefit.

    Date de mise en ligne : Mercredi 08 mars 2017
    Luca Vigano, Giovanni De Rosa, Christian Toso, Axel Andres, Alessandro Ferrero, Arnaud Roth, Elisa Sperti, Pietro Majno, Laura Rubbia-Brandt
    Reversibility of chemotherapy-related liver injury
    Although liver resection is the gold-standard treatment for patients with colorectal liver metastases,1–3 preoperative chemotherapy plays a crucial role in their management. It allows selection of appropriate candidates for surgery and treats occult disease foci; furthermore, it may reduce the size of lesions, enabling more conservative resections in patients with resectable lesions and achievement of resectability of some originally non-resectable lesions.4–9 The impact of preoperative chemotherapy on long-term outcomes needs to be explored further;10,11 however, it is already clear that tumor response to chemotherapy is one of the strongest prognostic factors after surgery.

    Date de mise en ligne : Mercredi 08 mars 2017
    Olivier Detry, Morgan Vandermeulen, Marie-Hélène Delbouille, Joan Somja, Noella Bletard, Alexandra Briquet, Chantal Lechanteur, Olivier Giet, Etienne Baudoux, Muriel Hannon, Frederic Baron, Yves Beguin
    Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I–II, open-label, clinical study
    Liver transplantation (LT) has become the gold standard treatment of many hepatic end-stage diseases. Long-term graft and patient survivals are now common after LT, but recipients are still subjected to life-long immunosuppression, which impairs quality of life and might reduce survival by promoting cancer development or by increasing the risks for infection, kidney function impairment and cardiovascular diseases. Therefore, there is a need for improvement in the immunosuppressive protocols after LT.

    Date de mise en ligne : Samedi 04 mars 2017
    Lauren A. Beste, Pamela K. Green, Kristin Berry, Matthew J. Kogut, Stephen K. Allison, George N. Ioannou
    Effectiveness of hepatitis C antiviral treatment in a USA cohort of veteran patients with hepatocellular carcinoma
    Hepatocellular carcinoma (HCC) mortality increased 72% in the United States (US) between 2003–2012, making it the fastest-growing cause of cancer-related mortality.1 HCC incidence also rose during this time, with a delay-adjusted average annual percentage change of 3.7%, second only to thyroid cancer nationally.1 HCV is implicated in the majority of HCC cases in the US.2–4 Until the widespread use of direct-acting antivirals (DAAs), antiviral treatment for patients with HCC and HCV was hampered by the poor efficacy and tolerability of interferon.

    Date de mise en ligne : Samedi 04 mars 2017
    Frank Tacke
    Targeting hepatic macrophages to treat liver diseases
    Some of the most pressing unresolved challenges in hepatology today can be related to an imbalance of inflammatory processes: (i) functional or biological cure from hepatitis B virus (HBV) infections can probably not be achieved without an effective antiviral immune response; (ii) the progression from non-alcoholic fatty liver to non-alcoholic steatohepatitis (NASH) with fibrosis is fuelled by chronic hepatic inflammation; (iii) patients with end-stage cirrhosis are prone to life-threatening bacterial infections indicating insufficient antimicrobial responses in the liver; finally, (iv) development and progression of hepatocellular carcinoma (HCC) is the result of inadequate tumor clearance and/or suppression of anti-tumor immunity [1].

    Date de mise en ligne : Samedi 04 mars 2017
    Hong Shen, Liang Sheng, Yi Xiong, Yeung-Hyen Kim, Lin Jiang, Zheng Chen, Yong Liu, Kalyani Pyaram, Cheong-Hee Chang, Liangyou Rui
    Thymic NF-κB-inducing kinase regulates CD4+ T cell-elicited liver injury and fibrosis in mice
    The liver is an immunologically-privileged organ. However, liver self-tolerance is compromised in autoimmune liver diseases, including primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis (AIH).1,2 Hepatic infiltration by T cells, particularly the cluster of differentiation [CD]4+ subpopulation, is reported to be associated with alcoholic liver disease, non-alcoholic steatohepatitis (NASH), and hepatotoxin-induced chronic liver injury in rodents and humans;3–7 however, the underlying mechanism responsible for the breakdown of liver immunological privilege is largely unknown.

    Date de mise en ligne : Samedi 04 mars 2017
    Henrike Julich-Haertel, Sabine K. Urban, Marcin Krawczyk, Arnulf Willms, Krzysztof Jankowski, Waldemar Patkowski, Beata Kruk, Maciej Krasnodębski, Joanna Ligocka, Robert Schwab, Ines Richardsen, Sebastian Schaaf, Angelina Klein, Sebastian Gehlert, Hanna Sänger, Markus Casper, Jesus M. Banales, Detlef Schuppan, Piotr Milkiewicz, Frank Lammert, Marek Krawczyk, Veronika Lukacs-Kornek, Miroslaw Kornek
    Cancer-associated circulating large extracellular vesicles in cholangiocarcinoma and hepatocellular carcinoma
    A decade ago extracellular vesicles (EVs) raised little attention in the scientific communities around the globe. Nowadays, EV research has become intense and acquired more attention, including within the liver research community.1,2 Over the years, researchers explored the likely role of EVs, including small EVs as exosomes (50–100nm in diameter)3 and large EVs, e.g. microvesicles/microparticles (MVs/MPs; 100–1000nm in diameter).4 Rarely, MVs/MPs were referred to as ‘ectosomes’.5 However, the underlying biogenesis of exosomes and MVs/MPs is different and unique.

    Date de mise en ligne : Vendredi 03 mars 2017
    Ângelo Zambam de Mattos, Angelo Alves de Mattos
    The Baveno VI criteria to identify patients not requiring endoscopic surveillance for esophageal varices – Should we use it?
    We are writing with regard to the article recently published by Maurice et al. [1] in the Journal of Hepatology. The authors described a cross-sectional study aimed at validating the Baveno VI criteria to identify patients not requiring endoscopic surveillance for esophageal varices. They reported that a combination of liver stiffness measurement under 20kPa and platelet count over 150,000/μl had a sensitivity of 87%, a specificity of 34% and an area under the receiver operating characteristic curve of 0.746 for ruling out high risk varices.

    Date de mise en ligne : Vendredi 03 mars 2017
    James Maurice, Massimo Pinzani, Emmanouil Tsochatzis, Rachel H. Westbrook
    Reply to: “The BAVENO VI criteria to identify patients not requiring endoscopic surveillance for esophageal varices – Should We use it?”
    We would like to thank Angelo Zamban De Mattos et al. for their interest and letter regarding our recently published manuscript.

    Date de mise en ligne : Vendredi 03 mars 2017
    Pierre Deltenre, Astrid Marot, Jean-François Knebel, Christopher Doerig, Jean Henrion, Christophe Moreno
    Effect of abstinence on the prognosis of patients with alcoholic liver disease: A word of caution
    We read the article by Lackner and collaborators [1] with great interest. The main goal of this study was to assess factors associated with long-term prognosis in patients with biopsy-proven alcoholic liver disease (ALD). Although this study is of major clinical relevance, we believe it deserves several comments.

    Date de mise en ligne : Vendredi 03 mars 2017
    Carolin Lackner, Andrea Berghold, Ramon Bataller, Rudolf E. Stauber
    Reply to: “Effect of abstinence on the prognosis of patients with alcoholic liver disease: A word of caution”
    We thank Deltenre et al. [1] for their interest in our study on long-term prognosis in patients with alcoholic liver disease (ALD) [2]. In response to their methodological concerns, we would like to clarify the following points:

    Date de mise en ligne : Mardi 28 fvrier 2017
    Gonzalo Sapisochin, Aisling Barry, Mark Doherty, Sandra Fischer, Nicolas Goldaracena, Roizar Rosales, Moises Russo, Rob Beecroft, Anand Ghanekar, Mamatha Bhat, James Brierley, Paul D. Greig, Jennifer J. Knox, Laura A. Dawson, David R. Grant
    Stereotactic body radiotherapy vs. TACE or RFA as a bridge to transplant in patients with hepatocellular carcinoma. An intention-to-treat analysis
    Liver transplantation (LT) represents the best treatment option for patients with selected hepatocellular carcinoma (HCC) but due to organ shortage most regions place limits on the size and number of tumors that qualify for this therapy. The best methods to prevent drop-out from the waiting list due to tumor progression and/or to reduce post-transplant tumor recurrence are unknown [1]. According to the American Association for the Study of Liver Diseases guidelines for the management of HCC, bridging therapies should be applied if the expected waiting time is longer than 6months [2].

    Date de mise en ligne : Dimanche 26 fvrier 2017
    Nikolaj Worm Ørntoft, Ole Lajord Munk, Kim Frisch, Peter Ott, Susanne Keiding, Michael Sørensen
    Hepatobiliary transport kinetics of the conjugated bile acid tracer 11C-CSar quantified in healthy humans and patients by positron emission tomography
    Bile acids are important for intestinal uptake of lipophilic compounds and regulation of metabolism.1–5 Since the major pool of bile acids undergoes enterohepatic circulation and de novo synthesis only plays a minor role, efficient hepatocellular uptake from blood and subsequent secretion into bile is essential to prevent hepatic and systemic accumulation of these potentially cytotoxic compounds.3,4 This becomes particularly evident in liver diseases associated with varying degrees of cholestasis.

    Date de mise en ligne : Vendredi 24 fvrier 2017
    Elisabeth Krones, Kathrin Eller, Marion J. Pollheimer, Silvia Racedo, Alexander H. Kirsch, Bianca Frauscher, Annika Wahlström, Marcus Ståhlman, Michael Trauner, Florian Grahammer, Tobias B. Huber, Karin Wagner, Alexander R. Rosenkranz, Hanns-Ulrich Marschall, Peter Fickert
    NorUrsodeoxycholic acid ameliorates cholemic nephropathy in bile duct ligated mice
    Impairment of renal function in liver disease represents a severe life-threatening event and may be related to numerous causes including hepatorenal syndrome (HRS) [1–4]. Patients with cirrhosis with concomitant infections and those with severe jaundice represent a high-risk group with dismal prognosis [5–8]. Notably, infection and cholestasis commonly co-exist as inflammation-induced cholestasis [9], and infection also represents a major trigger for acute on chronic liver failure (ACLF) [10].

    Date de mise en ligne : Jeudi 23 fvrier 2017
    Christine Bernsmeier, Emanuele Albano
    Liver dendritic cells and NAFLD evolution: A remaining open issue
    Due to the growing diffusion of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) is expected to become a major cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide within the next decade. However, the mechanisms responsible for NAFLD progression to non-alcoholic steatohepatitis (NASH) and fibrosis/cirrhosis are still largely unclear and this hampers the development of diagnostic tools to identify NAFLD patients’ at risk of progressive disease [1]. In the attempt to unravel the complex network responsible for sustaining lobular inflammation in NASH, growing attention has been given to liver myeloid cells including hepatic dendritic cells (HDCs), addressed by Heier et al.

    Date de mise en ligne : Jeudi 23 fvrier 2017
    Maite Merino-Azpitarte, Elisa Lozano, María J. Perugorria, Aitor Esparza-Baquer, Oihane Erice, Álvaro Santos-Laso, Colm J. O'Rourke, Jesper B. Andersen, Raúl Jiménez-Agüero, Adelaida Lacasta, Mauro D'Amato, Óscar Briz, Nidhi Jalan-Sakrikar, Robert C. Huebert, Kristen M. Thelen, Sergio A. Gradilone, Ana M. Aransay, José L. Lavín, Maite G. Fernández-Barrena, Ander Matheu, Marco Marzioni, Gregory J. Gores, Luis Bujanda, José J.G. Marin, Jesús M. Banales
    SOX17 regulates cholangiocyte differentiation and acts as a tumor suppressor in cholangiocarcinoma
    Cholangiocarcinoma (CCA) is a heterogeneous group of biliary malignancies with poor prognosis.1 The etiopathogenesis remains largely unknown.1 Incidence is rising worldwide and CCA already represents the second most common primary liver tumor and ∼3% of all gastrointestinal cancers.1 CCA is generally asymptomatic in early stages and is commonly diagnosed at advanced phases, when symptoms associated with biliary obstruction arise; this circumstance compromises the potential therapeutic options.1 Recurrence after surgery and elevated chemoresistance of CCAs contribute to the limited prognosis.

    Date de mise en ligne : Mardi 21 fvrier 2017
    Panu K. Luukkonen, You Zhou, P.A. Nidhina Haridas, Om P. Dwivedi, Tuulia Hyötyläinen, Ashfaq Ali, Anne Juuti, Marja Leivonen, Taru Tukiainen, Linda Ahonen, Emma Scott, Jeremy M. Palmer, Johanna Arola, Marju Orho-Melander, Petter Vikman, Quentin M. Anstee, Vesa M. Olkkonen, Matej Orešič, Leif Groop, Hannele Yki-Järvinen
    Impaired hepatic lipid synthesis from polyunsaturated fatty acids in TM6SF2 E167K variant carriers with NAFLD
    Common non-alcoholic fatty liver disease (NAFLD) is associated with features of the metabolic syndrome, such as hypertriglyceridemia, and increased risk of cardiovascular disease (CVD).1 In 2014, a non-synonymous adenine-to-guanine substitution (rs58542926) replacing glutamate at residue 167 with lysine (E167K) in the transmembrane 6 superfamily member 2 (TM6SF2) protein was shown to increase liver fat content2,3 and the risk of liver fibrosis.4 In these and several subsequent studies, variant allele carriers (TM6SF2EK/KK) were found to be neither more obese nor more insulin-resistant than non-carriers (TM6SF2EE).

    Date de mise en ligne : Mardi 21 fvrier 2017
    Lionel Piroth, Linda Wittkop, Karine Lacombe, Eric Rosenthal, Camille Gilbert, Patrick Miailhes, Patrizia Carrieri, Julie Chas, Isabelle Poizot-Martin, Anne Gervais, Stéphanie Dominguez, Didier Neau, David Zucman, Eric Billaud, Philippe Morlat, Hugues Aumaitre, Caroline Lascoux-Combe, Anne Simon, Olivier Bouchaud, Elina Teicher, Firouzé Bani-Sadr, Laurent Alric, Daniel Vittecoq, François Boué, Claudine Duvivier, Marc-Antoine Valantin, Laure Esterle, François Dabis, Philippe Sogni, Dominique Salmon, ANRS CO13 HEPAVIH study group
    Efficacy and safety of direct-acting antiviral regimens in HIV/HCV-co-infected patients – French ANRS CO13 HEPAVIH cohort
    Hepatitis C virus (HCV) co-infection is frequent among people living with HIV, with a reported prevalence of 15% to 30% 1–3 and up to 82% among injecting drug users.4 HCV co-infection has become a major cause of illness and death in the era of combination antiretroviral therapy (cART).5 Sustained virological responses (SVR) to interferon-based anti-HCV therapy used to be less frequent in cases of HIV co-infection.6–8 Since 2011, the treatment of chronic hepatitis C has improved dramatically with the advent of direct-acting antiviral (DAA) drugs.

    Date de mise en ligne : Vendredi 17 fvrier 2017
    Leon A. Adams, Richard K. Sterling
    Developing a new algorithm to diagnose advanced liver fibrosis: A lift or a nudge in the right direction?
    Accurate identification of liver disease severity and fibrosis stage is paramount in the management of those with chronic liver disease. In the past, this was often done by liver biopsy. However, due to its invasiveness and risks of bleeding, pain, and sampling error, non-invasive assessment of liver disease has gained increasing attention over the last decade. Non-invasive tests can be divided into serum tests and imaging tests. Although standard “liver function” tests, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are inaccurate when used alone, several models have been developed that use them in combination with other markers of advanced liver disease, such as platelet count.

    Date de mise en ligne : Vendredi 17 fvrier 2017
    Manuel Ramos-Casals, Anna Linda Zignego, Clodoveo Ferri, Pilar Brito-Zerón, Soledad Retamozo, Milvia Casato, Peter Lamprecht, Alessandra Mangia, David Saadoun, Athanasios G. Tzioufas, Zobair M. Younossi, Patrice Cacoub, International Study Group of Extrahepatic Manifestations related to HCV (ISG-EHCV)
    Evidence-based recommendations on the management of extrahepatic manifestations of chronic hepatitis C virus infection
    The hepatitis C virus (HCV), a linear, single-stranded RNA virus identified in 1989, is a hepatotropic virus that causes liver cirrhosis and hepatocellular cancer and is a global health problem. It is recognized as one of the hepatic viruses most often associated with the development of extrahepatic manifestations (EHMs), which can be classified according to the principal underlying etiopathogenic process (autoimmune, inflammatory, metabolic or neoplastic) [1]. HCV infected patients with extrahepatic involvement require a multidisciplinary approach and a complex therapeutic management.

    Date de mise en ligne : Jeudi 16 fvrier 2017
    Camille Blériot, Marc Lecuit
    RIPK1, a key survival factor for hepatocytes
    “A living cell is a cell that has succeeded day after day in suppressing, for a time yet, its self-destruction” [1]. Staying alive is a continuing struggle, at the cellular and multicellular level. During development and upon various stimuli, cell death can be essential for survival of multicellular organisms. Hundreds of millions of years of evolution have led to the selection of regulated cell death (RCD) mechanisms. The most famous RCD process, referred to as apoptosis, has been described during the early 1970s [2], and has been since shown to be involved in many developmental and physiological processes [3].

    Date de mise en ligne : Jeudi 16 fvrier 2017
    Søren S. Olesen, Clive D. Jackson, Marsha Y. Morgan
    Tools and tactics for improving the diagnosis of hepatic encephalopathy
    We read with interest the paper from Montagnese et al. (2016) on the possible use of two novel approaches to determine ‘neuropsychiatric normality’ in the context of a diagnosis of hepatic encephalopathy (HE) [1]. The authors challenge the conventional use of psychometric and neurophysiological testing based on reference to normative data and suggest that there may be advantages in defining ‘normality’ in terms of single patients’ lifelong performance and/or in terms of risk. Three cases serve as examples for the relevance of the suggested approaches.

    Date de mise en ligne : Jeudi 16 fvrier 2017
    Sara Montagnese, Michele De Rui, Paolo Angeli, Piero Amodio
    Reply to: “Tools and tactics for improving diagnosis of hepatic encephalopathy”
    We have read with interest the letter by Olesen and colleagues [1], and we are grateful to them for acknowledging that our two new proposals [2] have “merit”.

    Date de mise en ligne : Mardi 14 fvrier 2017
    Rohit Sinha, Khalida A. Lockman, Nethmee Mallawaarachchi, Marcus Robertson, John N. Plevris, Peter C. Hayes
    Carvedilol use is associated with improved survival in patients with liver cirrhosis and ascites
    Liver cirrhosis remains a leading cause of death worldwide. In the United Kingdom alone, mortality from liver cirrhosis has risen dramatically in the last decade tandem with the rise in alcohol consumption and the epidemic of obesity.1 Portal hypertension underlies many of its fatal complications. For this reason, non-selective beta-blockers (NSBBs) were proposed to be beneficial in the management of patients with varices. Their unselective beta-blockade reduces cardiac output and splanchnic blood flow while the unopposed effect of alpha 1 receptors leads to splanchnic vasoconstriction, thus reducing portal pressure and its attendant complications.

    Date de mise en ligne : Mardi 14 fvrier 2017
    Zhipeng Yan, Jing Zeng, Youjun Yu, Kunlun Xiang, Hui Hu, Xue Zhou, Lili Gu, Li Wang, Jie Zhao, John A.T. Young, Lu Gao
    HBVcircle: A novel tool to investigate hepatitis B virus covalently closed circular DNA
    Hepatitis B virus (HBV) is one of the most dangerous human pathogens. A safe and effective vaccine has been available for longer than two decades; however, approximately 2 billion people worldwide have been infected with HBV and more than 350 million people are chronically infected [1]. Chronic hepatitis B (CHB) infection predisposes its host to severe liver disease, including liver cirrhosis and hepatocellular carcinoma. HBV infection is ranked among the top health priorities worldwide. The currently approved drugs have contributed to substantial progress in CHB treatment; however, the cure rate remains less than 10% [2].

    Date de mise en ligne : Lundi 13 fvrier 2017
    Annalisa Berzigotti
    Non-invasive evaluation of portal hypertension using ultrasound elastography
    Portal hypertension (PH) leads to serious complications, such as bleeding from gastroesophageal varices, ascites and portosystemic encephalopathy in patients with chronic liver disease (CLD). Gold standard methods for assessing PH and its complications include the measurement of hepatic venous pressure gradient and endoscopy; however, these are invasive, expensive and not available at all centres. Therefore, non-invasive alternatives have been the subject of extensive investigation over the last 20years.

    Date de mise en ligne : Vendredi 10 fvrier 2017
    Giuseppe Cabibbo, Salvatore Petta, Marco Barbara, Simona Attardo, Laura Bucci, Fabio Farinati, Edoardo G. Giannini, Giulia Negrini, Francesca Ciccarese, Gian Lodovico Rapaccini, Maria Di Marco, Eugenio Caturelli, Marco Zoli, Franco Borzio, Rodolfo Sacco, Roberto Virdone, Fabio Marra, Andrea Mega, Filomena Morisco, Luisa Benvegnù, Antonio Gasbarrini, Gianluca Svegliati-Baroni, Francesco Giuseppe Foschi, Andrea Olivani, Alberto Masotto, Gerardo Nardone, Antonio Colecchia, Marcello Persico, Antonio Craxì, Franco Trevisani, Calogero Cammà, Italian Liver Cancer (ITA.LI.CA) group
    Hepatic decompensation is the major driver of death in HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma
    The prognosis of patients with cirrhosis due to hepatitis C virus (HCV) is decided by the progression towards hepatic decompensation and hepatocellular carcinoma (HCC), the latter being the leading cause of mortality in patients with compensated cirrhosis.1,2 Patients with cirrhosis due to HCV should be monitored for HCC regardless of HCV clearance. This would allow diagnosis of potentially curative early stage disease (Barcelona Clinic Liver Cancer [BCLC] stage 0 or A) using treatments, such as liver transplantation or, in most cases surgical resection or local ablation.

    Date de mise en ligne : Vendredi 10 fvrier 2017
    Barbara Oliviero, Stefania Mantovani, Stefania Varchetta, Dalila Mele, Giulia Grossi, Serena Ludovisi, Elisa Nuti, Armando Rossello, Mario U. Mondelli
    Hepatitis C virus-induced NK cell activation causes metzincin-mediated CD16 cleavage and impaired antibody-dependent cytotoxicity
    Natural killer (NK) cells are a major component of innate immunity, representing the first line of defense against pathogens and malignant cells. The activity of NK cells is finely tuned by several membrane receptors able to switch the NK function towards activation or inhibition after ligand recognition and interaction [1]. NK cells can recognize tumor or virus-infected cells without prior sensitization [2] and directly kill them by release of cytoplasmic granules containing cytolytic molecules, such as granzyme and perforin [3].

    Date de mise en ligne : Vendredi 10 fvrier 2017
    Suguru Yamashita, Junichi Shindoh, Takashi Mizuno, Yun Shin Chun, Claudius Conrad, Thomas A. Aloia, Jean-Nicolas Vauthey
    Hepatic atrophy following preoperative chemotherapy predicts hepatic insufficiency after resection of colorectal liver metastases
    For patients with colorectal liver metastases (CLM), the introduction of effective systemic therapy and an increase in the utilization of extensive hepatectomy have led to significant improvements in long-term survival during the past decades.1 However, while the perioperative mortality rate for hepatic resection is well below 5%, extensive preoperative chemotherapy remains a leading cause of morbidity and mortality.2–9

    Date de mise en ligne : Vendredi 10 fvrier 2017
    Hua Wu, Su Yao, Shen Zhang, Jing-Ru Wang, Peng-Da Guo, Xiu-Ming Li, Wen-Juan Gan, Lin Mei, Tian-Ming Gao, Jian-Ming Li
    Elevated expression of Erbin destabilizes ERα protein and promotes tumorigenesis in hepatocellular carcinoma
    Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world. Epidemiologically, the incidence of HCC in males is 2- to 11-fold higher than in females [1], and the male patients with HCC usually have a poorer prognosis than female patients with HCC [2], suggesting the roles of sex hormones and their receptors in HCC.

    Date de mise en ligne : Vendredi 10 fvrier 2017
    Ryo Nakagawa, Ryosuke Muroyama, Chisato Saeki, Kaku Goto, Yoshimi Kaise, Kazuhiko Koike, Masanori Nakano, Yasuo Matsubara, Keiko Takano, Sayaka Ito, Masayuki Saruta, Naoya Kato, Mikio Zeniya
    miR-425 regulates inflammatory cytokine production in CD4+ T cells via N-Ras upregulation in primary biliary cholangitis
    Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is a progressive autoimmune liver disease of unknown pathogenesis that predominantly affects middle-aged females [1–3]. Ursodeoxycholic acid (UDCA) treatment slows disease progression in most patients; nevertheless, 10years after diagnosis, approximately 32% of PBC patients in a late histologic stage and approximately 6% of patients in an early histologic stage, progress to liver transplantation or death due to liver failure [4].

    Date de mise en ligne : Vendredi 10 fvrier 2017
    Hannah K. Drescher, Angela Schippers, Thomas Clahsen, Hacer Sahin, Heidi Noels, Mathias Hornef, Norbert Wagner, Christian Trautwein, Konrad L. Streetz, Daniela C. Kroy
    β7-Integrin and MAdCAM-1 play opposing roles during the development of non-alcoholic steatohepatitis
    Currently, non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in Western countries. It is associated with human morbidity and mortality [1–3]. NAFLD in general encompasses a spectrum of hepatic alterations that begins with steatosis and can easily progress to more advanced degrees such as non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC) [4,5]. The growing medical need for therapy becomes clear if one considers that more than 20% of the general population have fatty livers and are thus at risk of developing NASH [6].

    Date de mise en ligne : Mercredi 08 fvrier 2017
    Jose Luis Calleja, Javier Crespo, Diego Rincón, Belén Ruiz-Antorán, Inmaculada Fernandez, Christie Perelló, Francisco Gea, Sabela Lens, Javier García-Samaniego, Begoña Sacristán, María García-Eliz, Susana Llerena, Juan Manuel Pascasio, Juan Turnes, Xavier Torras, Rosa Maria Morillas, Jordi Llaneras, Miguel A. Serra, Moises Diago, Conrado Fernández Rodriguez, Javier Ampuero, Francisco Jorquera, Miguel A. Simon, Juan Arenas, Carmen Alvarez Navascues, Rafael Bañares, Raquel Muñoz, Agustin Albillos, Zoe Mariño, The Spanish Group for the Study of the Use of Direct-acting Drugs Hepatitis C Collaborating Group
    Effectiveness, safety and clinical outcomes of direct-acting antiviral therapy in HCV genotype 1 infection: Results from a Spanish real-world cohort
    An estimated 130–170 million people globally are chronically infected with the hepatitis C virus (HCV), and are at significant risk of liver disease, cirrhosis and hepatocellular carcinoma (HCC) [1]. Successful treatment leading to a sustained virologic response (SVR) effectively cures HCV infection, significantly reducing the risk of HCV-related complications, liver transplantation, and death [2,3]. Interferon (IFN)-based therapies were associated with treatment-limiting side effects and resulted in SVR rates of 40–50% in patients with HCV genotype 1 infection [4], the most prevalent genotype worldwide [5].

    Date de mise en ligne : Mercredi 08 fvrier 2017
    Mei Zhou, Jian Luo, Michael Chen, Hong Yang, R. Marc Learned, Alex M. DePaoli, Hui Tian, Lei Ling
    Mouse species-specific control of hepatocarcinogenesis and metabolism by FGF19/FGF15
    The bile acid sensor, farnesoid X receptor (FXR), is a master regulator, controlling bile acid homeostasis, glucose and lipid metabolism, inflammation, and tissue repair [1,2]. Activation of FXR by synthetic ligands has demonstrated beneficial effects for treatment of patients with primary biliary cholangitis (PBC), non-alcoholic steatohepatitis (NASH), type 2 diabetes and non-alcoholic fatty liver disease [3–6]. FXR has recently been identified as a molecular target of vertical sleeve gastrectomy, and is thought to mediate metabolic improvements observed after bariatric surgery [7].

    Date de mise en ligne : Mercredi 08 fvrier 2017
    Kapish Gupta, Qiushi Li, Jun Jun Fan, Eliza Li Shan Fong, Ziwei Song, Shupei Mo, Haoyu Tang, Inn Chuan Ng, Chan Way Ng, Pornteera Pawijit, Shuangmu Zhuo, Chen-Yuan Dong, Boon Chuan Low, Aileen Wee, Yock Young Dan, Pakorn Kanchanawong, Peter So, Virgile Viasnoff, Hanry Yu
    Actomyosin contractility drives bile regurgitation as an early response during obstructive cholestasis
    The biliary function of the liver is critical for survival, serving to eliminate toxic endo- and xenobiotics, cholesterol, and inflammatory mediators [1]. The apical membranes of adjacent hepatocytes form the bile canalicular lumen, an intercellular structure surrounded by a dynamic pericanalicular actin cortex (PAC), which actively contracts to propel secreted biliary fluid towards the bile ducts [2,3]. A variety of liver diseases result in impaired bile flow, or obstructive cholestasis [4–7]. These include extrahepatic etiologies such as biliary strictures, stones and biliary atresia in infants; as well as intrahepatic causes that include primary biliary cirrhosis, vanishing duct syndrome, and alcoholic and viral hepatitis.

    Date de mise en ligne : Mercredi 08 fvrier 2017
    Qing-Lei Zeng, Guang-Hua Xu, Ji-Yuan Zhang, Wei Li, Da-Wei Zhang, Zhi-Qin Li, Hong-Xia Liang, Chun-Xia Li, Zu-Jiang Yu
    Generic ledipasvir-sofosbuvir for patients with chronic hepatitis C: A real-life observational study
    Chronic hepatitis C virus (HCV) infection is a major global health problem that affects 130–170 million people worldwide and represents a major cause of liver cirrhosis and hepatocellular carcinoma (HCC) [1–3]. In China, the overall prevalence of HCV infection is estimated to be 2.2% [1]. In Henan province, the incidence is 9.6% owing to a higher infection rate via blood transmission [1,2,4]. Genotype 1 is the most common in China, as it accounts for 58.4% of all HCV-infected persons, principally genotype 1b [1,2].

    Date de mise en ligne : Mercredi 08 fvrier 2017
    Ruth Zimmermann, Christian Kollan, Patrick Ingiliz, Stefan Mauss, Daniel Schmidt, Viviane Bremer
    Real-world treatment for chronic hepatitis C infection in Germany: Analyses from drug prescription data, 2010–2015
    Hepatitis C virus (HCV) infection is a worldwide problem; chronic HCV infection is one of the leading causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma.1–3 A rising burden of HCV-related morbidity and mortality has been reported from industrialized countries due to the accumulation of patients living with HCV infection long-term.4,5

    Date de mise en ligne : Mercredi 01 fvrier 2017
    Stacey B. Prenner, Lisa B. VanWagner, Steven L. Flamm, Riad Salem, Robert J. Lewandowski, Laura Kulik
    Hepatocellular carcinoma decreases the chance of successful hepatitis C virus therapy with direct-acting antivirals
    Hepatitis C virus (HCV) has been the leading cause of cirrhosis in the United States for several decades [1]. Until recently, the standard of care for HCV treatment was interferon based therapy (IFN), which was wrought with intolerable side effects, long treatment duration, and suboptimal sustained virologic response (SVR) rates of approximately 40% for patients with genotype 1 [2,3]. SVR rates were lower in patients with advanced fibrosis [4]. The approval of direct-acting antiviral agents (DAA) has subsequently revolutionized therapy for HCV.

    Date de mise en ligne : Mercredi 01 fvrier 2017
    Mette Vesterhus, Anders Holm, Johannes Roksund Hov, Ståle Nygård, Erik Schrumpf, Espen Melum, Liv Wenche Thorbjørnsen, Vemund Paulsen, Knut Lundin, Inge Dale, Odd Helge Gilja, Serge J.L.B. Zweers, Morten Vatn, Frank G. Schaap, Peter L.M. Jansen, Thor Ueland, Helge Røsjø, Bjørn Moum, Cyriel Y. Ponsioen, Kirsten Muri Boberg, Martti Färkkilä, Tom H. Karlsen, Fridtjof Lund-Johansen
    Novel serum and bile protein markers predict primary sclerosing cholangitis disease severity and prognosis
    Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressing inflammation and fibrosis of the intra- and extrahepatic bile ducts, leading to cirrhosis in the majority of patients. PSC is frequently associated with inflammatory bowel disease (IBD) and other immunological diseases. To date, liver transplantation is the only curative treatment in PSC, as there is no medical therapy of proven benefit to halt disease progression. The disease course is highly variable between PSC patients, with transplant-free survival ranging from 12–21years in different cohorts [1,2].

    Date de mise en ligne : Mercredi 01 fvrier 2017
    Stephen R. Atkinson, Michael J. Way, Andrew McQuillin, Marsha Y. Morgan, Mark R. Thursz
    Homozygosity for rs738409:G in PNPLA3 is associated with increased mortality following an episode of severe alcoholic hepatitis
    Cirrhosis is a major cause of global mortality, accounting for around one million deaths per annum.1 Alcohol misuse is the leading cause of cirrhosis in the Western world and is implicated in almost half of cirrhosis-related deaths.2

    Date de mise en ligne : Mercredi 25 janvier 2017
    Riccardo Lencioni, Robert Montal, Ferran Torres, Joong-Won Park, Thomas Decaens, Jean-Luc Raoul, Masatoshi Kudo, Charissa Chang, José Ríos, Valerie Boige, Eric Assenat, Yoon-Koo Kang, Ho-Yeong Lim, Ian Walters, Josep M. Llovet
    Objective response by mRECIST as a predictor and potential surrogate end-point of overall survival in advanced HCC
    In 60% of cases, patients with hepatocellular carcinoma (HCC) are diagnosed when tumors are no longer eligible for potentially curative therapies [1]. In this setting, only two treatments have been included in guidelines after demonstrating survival advantages in randomized controlled trials. Patients at an intermediate stage benefit from chemoembolization and have an estimated median overall survival (OS) of 26months [2], while at advanced stages, sorafenib extends survival from 8 to almost 11months [3].

    Date de mise en ligne : Samedi 21 janvier 2017
    Emmanuel A. Tsochatzis, Alexander L. Gerbes
    Diagnosis and treatment of ascites
    Ascites is the most common complication of cirrhosis and its development is a sign of significant portal hypertension.1 At a volume of more than 1.5l ascites usually can be detected by physical examination. Ascites in cirrhosis is the result of a vicious cycle involving arterial splanchnic vasodilation, decreased effective blood volume (despite a compensatory increase in cardiac output), renal vasoconstriction with resulting sodium retention, and finally extracellular fluid retention.2 Systemic inflammation can exacerbate portal hypertension, contribute to the development of ascites, and impair prognosis.

    Date de mise en ligne : Mardi 17 janvier 2017
    Eva-Carina Heier, Anna Meier, Henrike Julich-Haertel, Sonja Djudjaj, Monica Rau, Thomas Tschernig, Andreas Geier, Peter Boor, Frank Lammert, Veronika Lukacs-Kornek
    Murine CD103+ dendritic cells protect against steatosis progression towards steatohepatitis
    The prevalence of metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) in the last decade has increased dramatically worldwide and affects both adults and children [1–3]. Non-alcoholic fatty liver (NAFL) is characterized by fat accumulation that can progress towards non-alcoholic steatohepatitis (NASH) distinguished by intrahepatic inflammation, increased steatosis with hepatocellular ballooning and cellular damage [4]. The chronic inflammatory response in NASH often results in progressive fibrosis and cirrhosis, which predisposes individuals to hepatocellular carcinoma [5,6].

    Date de mise en ligne : Vendredi 13 janvier 2017
    Ameet Dhar, Benjamin H. Mullish, Mark R. Thursz
    Anticoagulation in chronic liver disease
    In this Grand Round presentation, the case of a man with decompensated liver disease is described. He subsequently developed a fatal pulmonary embolism, which may not have occurred if he had been prescribed prophylactic anticoagulation to prevent venous thromboembolic disease. The burden of thrombotic disease in those with chronic liver disease is discussed, before a more detailed analysis of the current evidence, safety data, and clinical dilemmas regarding the use of anticoagulation in patients with chronic liver disease.

    Date de mise en ligne : Vendredi 13 janvier 2017
    Aveline Filliol, Claire Piquet-Pellorce, Céline Raguénès-Nicol, Sarah Dion, Muhammad Farooq, Catherine Lucas-Clerc, Peter Vandenabeele, Mathieu J.M. Bertrand, Jacques Le Seyec, Michel Samson
    RIPK1 protects hepatocytes from Kupffer cells-mediated TNF-induced apoptosis in mouse models of PAMP-induced hepatitis
    The liver is constantly exposed to bacterial pathogen associated molecular patterns (PAMPs) such as unmethylated CpG-DNA motifs or lipopolysaccharides (LPS) originating from the microbiota of the gastrointestinal tract. In physiological conditions, the intestinal barrier prevents the translocation of large amounts of bacterial by-products to the liver [1]. The low quantities of bacterial debris reaching the liver are efficiently cleared by phagocytic hepatic cells, avoiding induction of inflammation and harmful response [2].

    Date de mise en ligne : Vendredi 13 janvier 2017
    Jérôme Boursier, Victor de Ledinghen, Vincent Leroy, Rodolphe Anty, Sven Francque, Dominique Salmon, Adrien Lannes, Sandrine Bertrais, Frederic Oberti, Isabelle Fouchard-Hubert, Paul Calès
    A stepwise algorithm using an at-a-glance first-line test for the non-invasive diagnosis of advanced liver fibrosis and cirrhosis
    Chronic liver diseases (CLD) are very common: worldwide, an estimated 160 million people have chronic hepatitis C [1], 240 million have chronic hepatitis B [2], and 25% of the general population has non-alcoholic fatty liver disease (NAFLD) [3]. CLD can lead to a progressive accumulation of fibrosis in the liver which progressively evolves to cirrhosis and its life-threatening complications such as hepatocellular carcinoma (HCC), liver failure, variceal bleeding, or renal insufficiency. In 2012, driven by the growing worldwide burden of CLD, cirrhosis was responsible for more than 35 million years of lost life and thus became the eleventh leading cause of mortality among non-communicable diseases [4].

    Date de mise en ligne : Lundi 18 fvrier 2013
    Shunji Nagai, Marcelo Facciuto, Shozo Mori, Mizuki Ninomiya, Juan P. Rocca, Alan Contreras-Saldivar, Myron E. Schwartz, Sander S. Florman
    WITHDRAWN: Recurrence prediction of hepatocellular carcinoma after liver transplantation by ischemia time and tumor characteristics
    This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

    Date de mise en ligne : Jeudi 01 janvier 1970
    The International Liver CongressTM. Paris, France, 2018

    Date de mise en ligne : Jeudi 01 janvier 1970
    EASL Clinical school of hepatology: Controversies in end-stage liver disease. Madrid, Spain, 2017

    Date de mise en ligne : Jeudi 01 janvier 1970
    Richard Moreau, Ramon Bataller, Thomas Berg, Jessica Zucmann-Rossi, Rajiv Jalan
    From the Editor’s desk...
    With the introduction of non-invasive tests, the reliance on liver biopsy to stage liver disease has declined substantially. Boursier et al. performed a hugely important study in over 3,000 patients, to develop and validate an algorithm for the assessment of the severity of fibrosis. The newly developed eLIFT test, which combines routine biochemical data and many tests of liver fibrosis, performed better that any other first line test. The FibroMeterVCTE (FMVCTE) was the most accurate among the eight, fibrosis tests evaluated.

    Date de mise en ligne : Jeudi 01 janvier 1970
    EASL Events 2017-2018

    Date de mise en ligne : Jeudi 01 janvier 1970
    EASL-AASLD Masterclass. Paris, France, 2017

    Date de mise en ligne : Jeudi 01 janvier 1970

    Date de mise en ligne : Jeudi 01 janvier 1970
    EASL First NAFLD summit: Target-oriented approach to diagnosis and pharmacotherapy of NASH, a dialogue between academia and industry. Rome, Italy, 2017

    Date de mise en ligne : Jeudi 01 janvier 1970
    EASL-AASLD joint meeting: Definition, therapeutic advances and clinical endpoints in alcoholic liver disease and alcoholic hepatitis. London, United Kingdom, 2017

    Date de mise en ligne : Jeudi 01 janvier 1970
    EASL funding; enhanced fellowship offer

    Date de mise en ligne : Jeudi 01 janvier 1970
    EASL Andrew K. Burroughs short-term training fellowships

    Date de mise en ligne : Jeudi 01 janvier 1970
    Editorial Board