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Mise à jour le : 30-03-2017




Les derniers abstracts de la revue Journal of Hepatology :


    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
    Summarized effects of ATF3 and in vivo-jetPEI ATF3 siRNA onthe oxidative stress-mediated hepatic steatosis and/or T2D.


    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 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
    Ectopic varices, rare but challenging
    We would like to thank the authors of this letter and for the interest in my article “Emergency TIPS in a Child-B patients: when opens and when closes the window of opportunity?” [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, nonalcoholic fatty liver disease (NAFLD) associated HCC is occupying a greater proportion of HCC incidence in recent decades [3].


    Date de mise en ligne : Vendredi 24 mars 2017
    Lai Qurino, Rossi Massimo, Lerut Jan
    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 MELD exception point system for hepatocellular cancer (HCC) patients waiting for liver transplantation (LT) [1]. The authors have to 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 8.6-month.


    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?
    To the Editor


    Date de mise en ligne : Jeudi 23 mars 2017
    Tania 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 >170 million people are affected worldwide and at risk for progressive liver disease and hepatocellular carcinoma [1,2]. HCV is classified into 7 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 [4].


    Date de mise en ligne : Mardi 21 mars 2017
    Morgan E. Preziosi, Sucha Singh, Erika V. Valore, Chun-Ling 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 healthy population in the US carry a mutation predisposing them to iron overload [1]. There is progressive accumulation of iron in parenchymal cells of various tissues due to mutations in key iron homeostasis genes. 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 eastern/South-eastern 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, Jose Serrano, Andrew Stolz, Ann Daly, Guruprasad Aithal, John Dillon, Victor Navarro, Joseph Odin, Huiman Barnhart, David Ostrov, Nanye Long, Elizabeth Theresa Cirulli, Paul Brent Watkins, Robert John Fontana, on behalf of the Drug-Induced Liver Injury Network (DILIN), the Pharmacogenetics of Drug-Induced Liver Injury group (DILIGEN) and the International Serious Adverse Events Consortium (iSAEC
    Minocycline Hepatotoxicity: Clinical characterization and identification of HLA-B∗ 35:02 as a risk factor
    Lay summary: Development of liver injury following prolonged use of minocycline for acne is a rare but potentially severe form of drug induced liver injury. Our study demonstrates that individuals who are HLA-B ∗35:02 carriers are at increased risk of developing minocycline related liver injury. These results may help doctors more rapidly and confidently diagnose affected patients and possibly reduce the risk of liver injury in individuals receiving minocycline going forward.


    Date de mise en ligne : Samedi 18 mars 2017
    Sílvia Vilarinho, 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 17 cm heterogeneous mass in the left lobe of the liver. She underwent left hepatectomy and pathology revealed a 14 cm 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 HCV treatments (Direct Acting Antivirals, DAAs) with >90% sustained viral response (SVR) rates in 8 to 12 weeks has ushered in an era of excitement about the possibility of elimination of 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 dramatic reduction in HCV incidence (∼50% in 2 years) among HIV-infected MSM in the Netherlands after the roll-out of DAA therapy[2] has provided the first piece of empirical evidence that HCV treatment as 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 tumour beyond TACE: from surgery to systemic therapy
    Intermediate stage hepatocellular carcinoma (HCC) comprises the largest subgroup of patients with this disease and is characterized by substantial heterogeneity. Functional liver impairment, total tumour burden and other prognostic factors such as high alpha-fetoprotein serum level, presence of micro-vascular invasion, and poorly differentiated tumours relevantly contribute to outcome. The usage of the standard therapeutic approach, transarterial chemoembolization – TACE, for all intermediate stage HCC patients is probably an over-simplification and may therefore not be appropriate for all patients.


    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 actionable mutations through next generation sequencing (NGS) facilitates implementation of target therapy [1]. This notion has sparked basket and umbrella trials that evaluate the off-label use of target agents in cancer patients bearing drugable mutations [2]. In hepatocellular carcinoma (HCC), only a minority of patients diagnosed at early stage can get curative treatments and for advanced HCCs, the standard therapy of sorafenib has a low response rate [3]. It’s thus of interest to explore if genomic profiling could help select HCC patients who may benefit from sorafenib or harbor mutations indicating the off-label use of other target drugs [4].


    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 Steato-Hepatitis, 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, apart from lifestyle changes, treatment of NAFLD is still elusive 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 and the Editor for the opportunity of responding to this letter.


    Date de mise en ligne : Mercredi 15 mars 2017
    Maurizia Brunetto, Markus Cornberg, Henry Lik Yuen Chan
    How Good Is Hepatitis B Surface Antigen Kinetics Informing Strategy to Stop Antiviral Therapy?
    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 x 100 persons/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 could be made
    We read we great interest the article by Lencioni et al entitled “Objective Response by mRECIST as a Predictor and Potential Surrogate End Point of Overall Survival in Advanced HCC”.


    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 M et al in this Journal [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 <100 IU/mL as a predictor for remote (6-10 years) HBsAg seroclearance but 2 studies on short-term prediction of HBsAg seroclearance within 1-3 years 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
    Assessment of 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] Treatment aims to induce a change in the evolution of the tumor, so that it translates into an improvement of 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; further, 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 [12–14].


    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 submitted 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 cardiovMSCular diseases. There is therefore a need for improvement in the immunosuppressive protocols after LT.


    Date de mise en ligne : Mercredi 08 mars 2017
    Vincent Mallet, Kamal Hamed, Michaël Schwarzinger
    Erratum to “Prognosis of patients with chronic hepatitis B in France (2008–2013): A nationwide, observational and hospital-based study”
    It has come to our attention that an error was introduced in Fig. 2 of this manuscript at the editorial stage of publication. The error consisted of the incorrect placement of the y axis, which should have intersected the x axis at 1. The corrected version of the figure may be found below. The editorial office would like to apologise for any inconvenience caused.


    Date de mise en ligne : Mardi 07 mars 2017
    Jordan J. Feld, Graham R. Foster
    Corrigendum to “Second generation direct-acting antivirals – do we expect major improvements?”
    It has come to our attention that an error was made in the section entitled “Next generation DAAs in development for specific populations – Chronic kidney disease”. The article reads:


    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 a dysbalance of inflammatory processes: (i) Functional or biological cure from hepatitis B virus 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 fueled by chronic hepatic inflammation; (iii) patients with end-stage cirrhosis are prone to life-threatening bacterial infections indicating insufficient antimicrobial responses in the liver; (iv) finally, development and progression of hepatocellular carcinoma 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 (NIK) 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 (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) [1,2]. Hepatic infiltration by T cells, particularly the CD4+ subpopulation, is reported to be associated with alcoholic liver disease, nonalcoholic 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 just little attention in the scientific communities around the globe. Nowadays, EV research has become intense and acquired more attention, including the liver research community [1,2]. Over the years, researchers explored the likely role of EVs, including small EVs as exosomes (50-100 nm in diameter) [3] and large EVs, e.g. microvesicles/microparticles (MVs/MPs; 100-1000 nm 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 [6].


    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 février 2017
    G. Sapisochin, A. Barry, M. Doherty, S. Fischer, N. Goldaracena, Roizar Rosales, Moises Russo, R. Beecroft, A. Ghanekar, M. Bhat, J. Brierley, P.D. Greig, J.J Knox, L.A. Dawson, D.R. Grant
    Stereotactic body radiotherapy versus 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 (AASLD) Guidelines for the management of HCC, bridging therapies should be applied if the expected waiting time is longer than 6 months[2].


    Date de mise en ligne : Dimanche 26 février 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 (PET)
    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 février 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]. Especially cirrhotic patients with concomitant infections and those deeply jaundiced represent a high-risk group with dismal prognosis [5–8]. Notably, infection and cholestasis commonly coexist 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 : Vendredi 24 février 2017
    Atsushi Oba, Shu Shimada, Yoshimitsu Akiyama, Taketo Nishikawaji, Kaoru Mogushi, Hiromitsu Ito, Satoshi Matsumura, Arihiro Aihara, Yusuke Mitsunori, Daisuke Ban, Takanori Ochiai, Atsushi Kudo, Hiroshi Asahara, Atsushi Kaida, Masahiko Miura, Minoru Tanabe, Shinji Tanaka
    ARID2 modulates DNA damage response in human hepatocellular carcinoma cells
    Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most leading cause of cancer-related death [1]. Chronic hepatitis and cirrhosis due to hepatitis B virus, hepatitis C virus infection, alcohol use, and metabolic diseases are the most prevalent risk factors for HCC, but the molecular mechanisms underlying hepatocarcinogenesis are complicated and remain unclear [1]. Recent genome-wide sequencing has identified recurrent mutations of chromatin-remodeling factors (25–60%) as well as TP53 (25–40%) and CTNNB1 (25–40%) mutations in HCC.


    Date de mise en ligne : Jeudi 23 février 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 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 février 2017
    M. Merino-Azpitarte, E. Lozano, M.J. Perugorria, A. Esparza-Baquer, O. Erice, A. Santos-Laso, C.J. O'Rourke, J.B. Andersen, R. Jiménez-Agüero, A. Lacasta, M. D'Amato, O. Briz, N. Jalan-Sakrikar, R.C. Huebert, K.M. Thelen, S.A. Gradilone, A.M. Aransay, J.L. Lavín, M.G. Fernández-Barrena, A. Matheu, M. Marzioni, G.J. Gores, L. Bujanda, J.J.G. Marin, J.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].


    Date de mise en ligne : Mardi 21 février 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 nonsynonymous adenine-to-guanine substitution (rs58542926) replacing glutamate at residue 167 with lysine (E167K) in transmembrane 6 superfamily member 2 (TM6SF2) was shown to increase liver fat content [2,3] 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) [2,5–12].


    Date de mise en ligne : Mardi 21 février 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 février 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 février 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, the International Study Group of Extrahepatic Manifestations related to HCV (ISG-EHCV) (See Appendix 1)
    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, 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 février 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 février 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 février 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 février 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 février 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 : Mardi 14 février 2017
    Antonella Mosca, Valerio Nobili, Rita De Vito, Annalisa Crudele, Eleonora Scorletti, Alberto Villani, Anna Alisi, Christopher D. Byrne
    Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents
    Non-alcoholic fatty liver disease (NAFLD) is now largely regarded as the hepatic manifestation of metabolic syndrome (MetS) and NAFLD represents the most frequent chronic liver disease in children in Western countries [1]. NAFLD begins with the development of liver lipid accumulation and the condition progresses over time with the development of liver inflammation and fibrosis (non-alcoholic steatohepatitis or NASH). Although it was initially thought that NAFLD was a relatively harmless condition in children and adolescents, recent evidence shows that NASH occurs in this young population [2].


    Date de mise en ligne : Lundi 13 février 2017
    Thomas Vanwolleghem, Andre Boonstra
    Focus on the liver: Host–virus interactions in HBV
    The hepatitis B virus (HBV) is a hepatotropic virus, yet most of the knowledge on its biology and the immune response induced by it are not obtained from liver studies, but rather from studies of blood. Since the cellular make-up of the liver is entirely different from blood, and since HBV exclusively replicates in the liver, the most relevant site to address the interaction of HBV with the host is the intrahepatic compartment.


    Date de mise en ligne : Lundi 13 février 2017
    Annalisa Berzigotti
    Non invasive evaluation of portal hypertension using ultrasound elastography
    Portal hypertension (PH) leads to serious complications such as bleeding from gastro-esophageal varices, ascites and porto-systemic encephalopathy in patients with chronic liver disease (CLD). Since the gold-standard methods for assessing PH and its complications (measurement of hepatic venous pressure gradient, HVPG; endoscopy), are invasive expensive and not available at all centers, non-invasive methods have been increasingly investigated in the last 20 years. The present review focuses on the role of ultrasound elastography, a novel group of non-invasive techniques able to measure stiffness in target organs, to identify the presence, severity and risk of complications of PH.


    Date de mise en ligne : Vendredi 10 février 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 février 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 février 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 février 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 février 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 février 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 février 2017
    Manuel Romero-Gómez, Helena Cortez-Pinto
    Detecting liver fat from viscoelasticity: How good is CAP in clinical practice? The need for universal cut-offs
    Detecting and quantifying hepatic steatosis has been a long-term challenge. Hepatocyte steatosis is the hallmark of non-alcoholic fatty liver disease (NAFLD) but also could play a prognostic role in several other liver diseases like viral hepatitis, hemochromatosis, Wilson disease or even autoimmune hepatitis. The presence of steatosis has been associated with faster fibrosis progression [1]. Thus, further development of non-invasive methods to detect and quantify hepatic steatosis is both an unmet need, and a challenge.


    Date de mise en ligne : Mercredi 08 février 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 février 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 février 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 février 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 février 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 08 février 2017
    Carlo Ferrari, Carolina Boni, Marzia Rossi, Andrea Vecchi, Valeria Barili, Diletta Laccabue, Paola Fisicaro, Gabriele Missale
    T cell regulation in HBV-related chronic liver disease
    HBV-specific T cell dysfunction is believed to play a central role in the pathogenesis of chronic HBV persistence [1,2]. HBV-specific T cells are more dysfunctional within the liver than in the periphery [3] as a result of the inhibitory effect of different mechanisms. They are likely to be active simultaneously within the inflamed liver together contributing to T cell functional impairment [4,5]. Some of them have been directly characterized in HBV infection, while others are assumed to be relevant because of their general importance within the liver.


    Date de mise en ligne : Lundi 06 février 2017
    Srinivasan Dasarathy, Manuela Merli
    Reply to: Myokines: a promising therapeutic target for hepatic encephalopathy
    We read with great interest the letter by Yang and Luo on our work on hyperammonemia-mediated regulation of skeletal muscle mass and function [1]. We have previously reported that hyperammonemia transcriptionally upregulates myostatin in the skeletal muscle and that it results in impaired protein synthesis [2]. Myostatin is believed to be a myokine, and circulating myostatin levels are elevated in cirrhosis [2,3]. However, there is currently no evidence to support a direct cerebral effect of myostatin beyond that related to its effects on the skeletal muscle.


    Date de mise en ligne : Vendredi 03 février 2017
    Chun Yang, Ai-Lin Luo
    Myokines: A promising therapeutic target for hepatic encephalopathy
    Recently, we read with great interest the review by Dasarathy and Merli [1] and the editorial by Rombouts et al. [2] regarding the effects of hyperammonemia on muscle activity and mass. These authors suggested a beneficial role of muscle in the prevention and treatment of hepatic encephalopathy (HE) by inhibiting wasting of muscle mass and facilitating muscle protein synthesis. We agree with their conclusion, and that this possibility provides a novel alternative for clinical treatment of HE.


    Date de mise en ligne : Vendredi 03 février 2017
    Auvro R. Mridha, Alexander Wree, Avril A.B. Robertson, Matthew M. Yeh, Casey D. Johnson, Derrick M. Van Rooyen, Fahrettin Haczeyni, Narci C.-H. Teoh, Christopher Savard, George N. Ioannou, Seth L. Masters, Kate Schroder, Matthew A. Cooper, Ariel E. Feldstein, Geoffrey C. Farrell
    NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice
    Non-alcoholic fatty liver disease (NAFLD) increases standardised mortality from cardiovascular events, common cancers, cirrhosis and hepatocellular carcinoma [1,2]. Adverse liver outcomes are confined to the 10–25% of NAFLD patients with liver fibrosis, particularly with the pathology of steatohepatitis (NASH) [3,4]. NASH occurs when overnutrition is complicated by insulin resistance and metabolic syndrome [2,5,6], particularly with a personal or family history of type 2 diabetes. Despite these connections, detailed mechanisms linking metabolic obesity to liver pathology are unclear.


    Date de mise en ligne : Vendredi 03 février 2017
    EASL Recommendations for Treatment of Hepatitis C 2016 Panel
    Reply to: Contradictory advice for people who inject drugs in the 2016 EASL Recommendations on Treatment of Hepatitis C
    The EASL Recommendations for Treatment of Hepatitis C 2016 Panel read with interest the letter by Grebely et al. pointing to supposedly contradictory advice on HCV therapy in people who inject drugs (PWIDs). The panel does not see any contradiction in the recommendations. EASL recommends that “All treatment-naïve and treatment-experienced patients with compensated or decompensated chronic liver disease related to HCV, who are willing to be treated and who have no contraindications to treatment, must be considered for therapy”.


    Date de mise en ligne : Vendredi 03 février 2017
    Jason Grebely, Tracy Swan, Matthew Hickman, Julie Bruneau, Philip Bruggmann, Olav Dalgard, Alain Litwin, Markus Backmund, Gregory J. Dore, International Network for Hepatitis in Substance Users
    Contradictory advice for people who inject drugs in the 2016 EASL Recommendations on Treatment of Hepatitis C
    The 2016 EASL Recommendations on Treatment of Hepatitis C provide important international guidance for the clinical management of HCV infection. The guidance is crucial in the environment of rapidly changing direct-acting antiviral (DAA) therapeutics. However, there are inherent contradictions within the EASL Recommendations for people who inject drugs (PWID). The EASL Recommendations state that “Treatment should be considered without delay in individuals at risk of transmitting HCV (e.g., active injection drug users)”, given the potential for preventing HCV transmission and reductions in HCV prevalence at a population-level.


    Date de mise en ligne : Mercredi 01 février 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 février 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 février 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 : Lundi 23 janvier 2017
    Agrin Moeini, Daniela Sia, Zhongyang Zhang, Genis Camprecios, Ashley Stueck, Hui Dong, Robert Montal, Laura Torrens, Iris Martinez-Quetglas, M. Isabel Fiel, Ke Hao, Augusto Villanueva, Swan N. Thung, Myron E. Schwartz, Josep M. Llovet
    Mixed hepatocellular cholangiocarcinoma tumors: Cholangiolocellular carcinoma is a distinct molecular entity
    Liver cancer is the second leading cause of cancer-related deaths, with more than 850,000 new cases annually worldwide [1]. Mixed hepatocellular cholangiocarcinoma (HCC-CCA) is a rare type of primary liver cancer accounting for less than 1% of all primary liver malignancies [2,3]. Diagnosis is based on histological examination and requires the intimate mix of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) elements [2]. Due to its low incidence and the lack of an established pathological diagnosis, the features and clinical behavior of these tumors remain ill-defined.


    Date de mise en ligne : Lundi 23 janvier 2017
    Michelle J. Farquhar, Isla S. Humphreys, Simon A. Rudge, Garrick K. Wilson, Bishnupriya Bhattacharya, Maria Ciaccia, Ke Hu, Qifeng Zhang, Laurent Mailly, Gary M. Reynolds, Margaret Ashcroft, Peter Balfe, Thomas F. Baumert, Stephanie Roessler, Michael J.O. Wakelam, Jane A. McKeating
    Autotaxin-lysophosphatidic acid receptor signalling regulates hepatitis C virus replication
    Chronic viral hepatitis is a global health problem with at least 170 million hepatitis C virus (HCV) infected individuals at risk of developing liver disease that can progress to hepatocellular carcinoma (HCC). The recent availability of direct-acting antiviral agents can eliminate HCV in up to 90% of patients [1]. However, the high cost of these drugs along with reports of viral genotype resistance, may limit their wide-spread use. Importantly, patients with liver cirrhosis cured of HCV may remain at risk of developing HCC, highlighting the need to understand host pathways playing a role in HCC development [2,3].


    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 : Mardi 17 janvier 2017
    Stefan Zeuzem, Masashi Mizokami, Stephen Pianko, Alessandra Mangia, Kwang-Hyub Han, Ross Martin, Evguenia Svarovskaia, Hadas Dvory-Sobol, Brian Doehle, Charlotte Hedskog, Chohee Yun, Diana M. Brainard, Steven Knox, John G. McHutchison, Michael D. Miller, Hongmei Mo, Wan-Long Chuang, Ira Jacobson, Gregory J. Dore, Mark Sulkowski
    NS5A resistance-associated substitutions in patients with genotype 1 hepatitis C virus: Prevalence and effect on treatment outcome
    Due to high rates of viral replication and an error prone hepatitis C virus (HCV) RNA polymerase, tremendous variability of HCV has been observed within infected patients (quasispecies). These single mutations that do not abolish viral replication, are thought to be pre-existing [1] and as a result, NS5A resistance-associated substitutions (RASs) are observed at baseline in patients infected with chronic HCV. Deep sequencing enables detection of HCV substitutions, point deletions, or insertions within the quasispecies down to a frequency of 1%.


    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
    Maria Sandbothe, Reena Buurman, Nicole Reich, Luisa Greiwe, Beate Vajen, Engin Gürlevik, Vera Schäffer, Marlies Eilers, Florian Kühnel, Alejandro Vaquero, Thomas Longerich, Stephanie Roessler, Peter Schirmacher, Michael P. Manns, Thomas Illig, Brigitte Schlegelberger, Britta Skawran
    The microRNA-449 family inhibits TGF-β-mediated liver cancer cell migration by targeting SOX4
    Hepatocellular carcinoma (HCC) accounts for approximately 80% of all primary liver cancers [1]. It is the second most common cause of cancer-related death worldwide, estimated to be responsible for 745,000 deaths in 2012 alone [2]. While patients with early HCC benefit from interventional therapies such as resection or liver transplantation, patients with advanced HCC are mainly treated palliatively with very limited treatment options [3,4]. The only systemic therapy available for advanced HCC is the multikinase inhibitor sorafenib [5].


    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 09 janvier 2017
    Joanna Hanley, Dipok Kumar Dhar, Francesca Mazzacuva, Rebeca Fiadeiro, Jemima J. Burden, Anne-Marie Lyne, Holly Smith, Anna Straatman-Iwanowska, Blerida Banushi, Alex Virasami, Kevin Mills, Frédéric P. Lemaigre, A.S. Knisely, Steven Howe, Neil Sebire, Simon N. Waddington, Coen C. Paulusma, Peter Clayton, Paul Gissen
    Vps33b is crucial for structural and functional hepatocyte polarity
    In metazoans, the development of three-dimensional body structures depends on the generation of polarised epithelial layers. Polarisation of epithelial cells is a complex process that requires the cooperation of multiple factors including cell junction formation, extracellular matrix interactions and intracellular protein trafficking [1]. Correct interaction of these factors enables the establishment of discrete apical and basolateral membrane domains. This then promotes normal epithelial cell function by allowing directional solute absorption and secretion [2].


    Date de mise en ligne : Samedi 31 décembre 2016
    Fanny Lebossé, Barbara Testoni, Judith Fresquet, Floriana Facchetti, Enrico Galmozzi, Maëlenn Fournier, Valérie Hervieu, Pascale Berthillon, Françoise Berby, Isabelle Bordes, David Durantel, Massimo Levrero, Pietro Lampertico, Fabien Zoulim
    Intrahepatic innate immune response pathways are downregulated in untreated chronic hepatitis B patients
    More than 240 million people are chronically infected with hepatitis B virus (HBV) worldwide [1]. Chronic hepatitis B (CHB) can evolve towards liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC), which is responsible for over 0.5–1 million deaths per year [2]. Viral persistence is mostly ascribed to the intrahepatic pool of covalently closed circular DNA (cccDNA), which represents the unique template for HBV replication [3–5]. Currently available therapies fail to clear intrahepatic cccDNA.


    Date de mise en ligne : Mercredi 28 décembre 2016
    Thomas Karlas, David Petroff, Magali Sasso, Jian-Gao Fan, Yu-Qiang Mi, Victor de Lédinghen, Manoj Kumar, Monica Lupsor-Platon, Kwang-Hyub Han, Ana C. Cardoso, Giovanna Ferraioli, Wah-Kheong Chan, Vincent Wai-Sun Wong, Robert P. Myers, Kazuaki Chayama, Mireen Friedrich-Rust, Michel Beaugrand, Feng Shen, Jean-Baptiste Hiriart, Shiv K. Sarin, Radu Badea, Kyu Sik Jung, Patrick Marcellin, Carlo Filice, Sanjiv Mahadeva, Grace Lai-Hung Wong, Pam Crotty, Keiichi Masaki, Joerg Bojunga, Pierre Bedossa, Volker Keim, Johannes Wiegand
    Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis
    Hepatic steatosis is a frequent finding in chronic liver diseases of different etiologies such as viral hepatitis and alcoholic liver disease, and its prevalence is increasing along with the worldwide epidemic of non-alcoholic fatty liver disease (NAFLD) [1–4].


    Date de mise en ligne : Mercredi 28 décembre 2016
    Bettina Langhans, Hans Dieter Nischalke, Benjamin Krämer, Annekristin Hausen, Leona Dold, Peer van Heteren, Robert Hüneburg, Jacob Nattermann, Christian P. Strassburg, Ulrich Spengler
    Increased peripheral CD4+ regulatory T cells persist after successful direct-acting antiviral treatment of chronic hepatitis C
    Chronic hepatitis C virus (HCV) infection is a major global health problem, because it leads to liver fibrosis, cirrhosis and liver cancer [1]. The T cell balance between stimulatory and immunosuppressive mechanisms seems to critically determine outcomes of HCV infection [2]. During chronic hepatitis C effector T cells become progressively exhausted and exhibit reduced antiviral activity, while CD4+ regulatory T cells (Tregs) gradually expand and accumulate in the liver [3]. Tregs suppress antiviral T cell responses [4–7], inhibit activation of natural killer (NK) cells [8], activate fibrogenesis in hepatic stellate cells [9,10] and ultimately facilitate liver cancer [11].


    Date de mise en ligne : Mercredi 28 décembre 2016
    Emmanuel Weiss, Pierre-Emmanuel Rautou, Magali Fasseu, Mikhael Giabicani, Marc de Chambrun, JingHong Wan, Charlotte Minsart, Thierry Gustot, Alain Couvineau, Rakhi Maiwall, Margarita Hurtado-Nedelec, Nathalie Pilard, Didier Lebrec, Dominique Valla, François Durand, Pierre de la Grange, Renato C. Monteiro, Catherine Paugam-Burtz, Sophie Lotersztajn, Richard Moreau
    Type I interferon signaling in systemic immune cells from patients with alcoholic cirrhosis and its association with outcome
    Type I interferons (IFNs) are a family of cytokines that play a crucial role in the immune response to viral pathogens [1]. They mediate virus detection by intracellular or extracellular sensors and the activation of antiviral mechanisms, via an autocrine/paracrine signaling (Fig. 1) [2]. IFNs engage canonical signaling pathways through a common heterodimeric receptor (IFNAR1/IFNAR2) [3]. Receptor subunits are associated with the kinases JAK1 and TYK2, and activation of these kinases results in phosphorylation of STAT1 and STAT2, which then associate with IFN regulatory factor (IRF)9 to form the IFN-stimulated gene factor (ISGF)3 complex activating the transcription of IFN-stimulated genes (ISGs) [4,5].


    Date de mise en ligne : Samedi 24 décembre 2016
    Kyle A. Soltys, Kentaro Setoyama, Edgar N. Tafaleng, Alejandro Soto Gutiérrez, Jason Fong, Ken Fukumitsu, Taichiro Nishikawa, Masaki Nagaya, Rachel Sada, Kimberly Haberman, Roberto Gramignoli, Kenneth Dorko, Veysel Tahan, Alexandra Dreyzin, Kevin Baskin, John J. Crowley, Mubina A. Quader, Melvin Deutsch, Chethan Ashokkumar, Benjamin L. Shneider, Robert H. Squires, Sarangarajan Ranganathan, Miguel Reyes-Mugica, Steven F. Dobrowolski, George Mazariegos, Rajavel Elango, Donna B. Stolz, Stephen C. Strom, Gerard Vockley, Jayanta Roy-Chowdhury, Marilia Cascalho, Chandan Guha, Rakesh Sindhi, Jeffrey L. Platt, Ira J. Fox
    Host conditioning and rejection monitoring in hepatocyte transplantation in humans
    Transplantation of isolated hepatocytes has been proposed as a minimally invasive alternative to organ transplantation for acute liver failure and liver-based metabolic deficiencies [1]. Hepatocytes have been safely transplanted into the liver, have produced partial correction of Crigler-Najjar syndrome type 1 [2], factor VII deficiency [3], urea cycle disorders (UCD) [4,5], infantile Refsum’s disease [6], glycogen storage disease type 1 [7], and phenylketonuria (PKU) [8], and have been associated anecdotally with reversal of acute hepatic failure [1].


    Date de mise en ligne : Vendredi 23 décembre 2016
    Michaela Wittlich, Michael Dudek, Jan P. Böttcher, Oliver Schanz, Silke Hegenbarth, Tobias Bopp, Edgar Schmitt, Christian Kurts, Christoph Garbers, Stefan Rose John, Percy A. Knolle, Dirk Wohlleber
    Liver sinusoidal endothelial cell cross-priming is supported by CD4 T cell-derived IL-2
    Induction of antigen-specific immunity by CD8 T cells requires appropriate activation and maturation of antigen-presenting cells such as dendritic cells (DCs). Activation of DCs through Toll-like receptors or pro-inflammatory mediators like type I interferon induces their functional maturation, which is characterized by an upregulation of co-stimulatory molecules, e.g., CD80/CD86 or CD40, and increased expression of IL-12 [1,2]. Such functional maturation is operational in improving DC capacity to cross-prime naïve CD8 T cells towards soluble antigens and to mount protective immunity [3].


    Date de mise en ligne : Lundi 12 décembre 2016
    Kun Huang, Meng Du, Xin Tan, Ling Yang, Xiangrao Li, Yuhan Jiang, Cheng Wang, Fengxiao Zhang, Feng Zhu, Min Cheng, Qinglin Yang, Liqing Yu, Lin Wang, Dan Huang, Kai Huang
    PARP1-mediated PPARα poly(ADP-ribosyl)ation suppresses fatty acid oxidation in non-alcoholic fatty liver disease
    Non-alcoholic fatty liver disease (NAFLD) covers a broad spectrum of liver abnormalities ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis [1]. The prevalence of NAFLD is increasing globally, and becoming the predominant cause of chronic liver disease in many parts of the world [2]. The hallmark of NAFLD is an over-accumulation of triglycerides-rich lipid droplets in the hepatocytes of liver due to deregulation of hepatic lipid metabolism, including increased fatty acid (FA) uptake and synthesis as well as insufficient disposal (i.e., oxidation and secretion).


    Date de mise en ligne : Mardi 29 novembre 2016
    Sven Pischke, Johannes Hartl, Suzan D. Pas, Ansgar W. Lohse, Bart C. Jacobs, Annemiek A. Van der Eijk
    Hepatitis E virus: Infection beyond the liver?
    Hepatitis E virus (HEV) infections are not limited to the liver but may also affect other organs. Several diseases, including Guillain-Barré syndrome, neuralgic amyotrophy, glomerulonephritis, cryoglobulinemia, pancreatitis, lymphoma, thrombopenia, meningitis, thyroiditis and myocarditis have been observed in the context of hepatitis E. To date, the definite pathophysiological links between HEV and extrahepatic manifestations are not yet established. However, it is suggested that HEV infection might be causative based on serological studies, case series, in vitro data and animal models.


    Date de mise en ligne : Lundi 18 février 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.