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Les derniers abstracts de la revue Journal of Hepatology :


    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 affect both adults and children[1–3]. 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 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 HCV RNA polymerase, tremendous variability of HCV has been observed within infected patients (quasispecies) with all single mutations that do not abolish viral replication thought to be pre-existing [1]. As a result, NS5A 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%. However, commercially available assays based on standard population HCV sequencing or not cross-validated next generation, also called deep sequencing, report variants with a frequency of ⩾15% of the quasispecies.


    Date de mise en ligne : Vendredi 13 janvier 2017
    Ameet Dhar, Benjamin H. Mullish, Mark R. Thursz
    Grand Round: Anticoagulation in Chronic Liver Disease
    In this Grand Round, we first present a case of a man with decompensated liver disease who subsequently developed a fatal pulmonary embolism, having not been prescribed prophylactic anticoagulation to prevent venous thromboembolic disease. We go on to discuss the burden of thrombotic disease in those with chronic liver disease, before a more detailed discussion regarding the current evidence, safety data, and clinical dilemmas regarding the use of anticoagulation in patients with chronic liver disease, as well as discussing potential future directions within this field.


    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 condition, the intestinal barrier prevents the translocation of large amount of bacterial by-products to the liver [1]. The low quantities of bacterial debris reaching the liver are efficiently cleared by phagocytic hepatic cells, which avoids 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 a 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
    Thomas Klag, Julia Dietz, Christoph R. Werner, Julia M. Schwarz, Ulrich M. Lauer, Robert Beck, Nisar P. Malek, Christoph Sarrazin, Christoph P. Berg
    Hepatitis C “true” late relapse beyond 48 weeks of sustained virologic response after direct acting antiviral therapy
    With great interest we read the 2016 EASL recommendations for treatment of hepatitis C [1]. These guidelines recommend that patients who achieve a sustained virologic response (SVR, defined as undetectable HCV-RNA in blood 12 or 24 weeks after end of treatment) should be retested for HCV-RNA at 48 weeks post end of treatment. When HCV-RNA is then negative, hepatitis C is defined as being definitely cured, thereby terminating any further analysis for presence/absence of HCV RNA. Only in special risk groups such as PWID (people who inject drugs) or MSM (men who have sex with men) further HCV-RNA testings should be performed beyond SVR 48 on an annual base [1].


    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, AS. Knisely, Steven Howe, Neil Sebire, Simon 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 : Lundi 09 janvier 2017
    Michael Bitzer, Helmut R. Salih
    Reply to “Histone deacetylase inhibitor for the treatment of hepatocellular carcinoma: chemoimmunotherapeutic perspective and prospects”
    We thank Drs. Goto and Kato for their thoughtful comments on our study, in particular their remarks on possible immunotherapeutic consequences of treatment with histone deacetylase inhibitors [1]. They speculate that reinforcement of NK cell immunity may constitute an additional mechanism by which the histone deacetylase inhibitor (HDACi) Resminostat, in combination with the tyrosine kinase inhibitor (TKI) Sorafenib achieved a high disease control rate in our second line study in HCC [2]. Their hypothesis is based on their own findings that MICA, a ligand of the activating immunoreceptor NKG2D, is upregulated upon treatment of cancer cells with different HDACi [3] and the observation of others that membrane-bound MICA is increased by Sorafenib via reduction of a disintegrin and metalloproteinase 9 (ADAM9), resulting in diminished shedding from the cell surface [4].


    Date de mise en ligne : Lundi 09 janvier 2017
    Kaku Goto, Naoya Kato
    Histone deacetylase inhibitor for the treatment of hepatocellular carcinoma: chemoimmunotherapeutic perspective and prospects
    To the Editor:


    Date de mise en ligne : Vendredi 06 janvier 2017
    Wei-Tien Tai, Ann-Lii Cheng, Chung-Wai Shiau, Hsiang-Po Huang, Jui-Wen Huang, Pei-Jer Chen, Kuen-Feng Chen
    Corrigendum to “Signal transducer and activator of transcription 3 is a major kinase-independent target of sorafenib in hepatocellular carcinoma”
    After careful examination of the raw data included in this manuscript, we found that the Western blots of the internal control, actin, in Fig. 3B and C were the same as the Fig. 2D. We have corrected this error in the revised Fig. 3 below. In addition, the expression level of SOCS-1 and SOCS-3 in Fig. 4E should be under sorafenib 5μM and 10μM treatments, rather than sorafenib and SC-1 treatment. The corrected version of Fig. 4 is also included below.


    Date de mise en ligne : Jeudi 05 janvier 2017
    Dewei Ye, Kangmin Yang, Shufei Zang, Zhuofeng Lin, Hau-Tak Chau, Yudong Wang, Jialiang Zhang, Junping Shi, Aimin Xu, Shaoqiang Lin, Yu Wang
    Corrigendum to “Lipocalin-2 mediates non-alcoholic steatohepatitis by promoting neutrophil-macrophage crosstalk via the induction of CXCR2”
    An error was introduced in Fig. 6C of the original manuscript. During preparation of Fig. 6C, the representative image of “HFHC+Rm-LCN2-CXCR2 KO” group was inadvertently duplicated in lieu of the representative image for “SC-CXCR2 KO” group. The corrected immunohistochemistry images shown in the updated Fig. 6, are provided below. The authors apologize for any inconvenience caused.


    Date de mise en ligne : Samedi 31 décembre 2016
    Erfan Ayubi, Saeid Safiri, Mohadeseh Sani, Salman Khazaei, Kamyar Mansori
    Heavy daily alcohol intake at the population level predicts the weight of alcohol in cirrhosis burden worldwide: methodological issues of confounding and prediction models
    We were interested to read paper entitled “Heavy daily alcohol intake at the population level predicts the weight of alcohol in cirrhosis burden worldwide”published by Stein and colleagues in the Journal of Hepatologyin 2016[1]. The authors aimed to evaluate the associations between population drinking, cirrhosis cofactors, and economic indicators and the burden of alcoholic cirrhosis on a population level. They found that heavy daily drinking had statistically significant effect on the weight of alcohol in the cirrhosis burden, however, the results suggested that higher gross domestic product (GDP) may decrease alcohol-attributable fraction (AAF) of cirrhosis[1].


    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 down-regulated in untreated chronic hepatitis B
    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), being 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 : Samedi 31 décembre 2016
    Monica Cruz-Lemini, Jose Altamirano, Nambi Ndugga, Juan G. Abraldes, Ramon Bataller
    Reply to: Heavy daily alcohol intake at the population level predicts the weight of alcohol in cirrhosis burden worldwide: methodological issues of confounding and prediction models
    We would like to thank Dr Ayubi and colleagues for their constructive comments on our paper [1]. First, they hypothesize that ethnicity might be confounding the association between GDP and alcohol-attributable fraction (AAF), since ethnicity might determine susceptibility to alcohol damage [2] and at the same time might be associated with GDP. Unfortunately, with the available data we cannot test this hypothesis, since the WHO data is grouped by country, and assigning a specific ethnicity to a country would be challenging.


    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 (hereafter called 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 anti-viral 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 IRF9 to form the ISGF3 complex activating the transcription of IFN-stimulated genes (ISGs) [4,5].


    Date de mise en ligne : Mardi 27 décembre 2016
    Inmaculada Fernández, Raquel Muñoz-Gómez, Juan M. Pascasio, Carme Baliellas, Natalia Polanco, Nuria Esforzado, Ana Arias, Martín Prieto, Lluis Castells, Valentín Cuervas-Mons, Olga Hernández, Javier Crespo, José L Calleja, Xavier Forns, María-Carlota Londoño
    Efficacy and tolerability of interferon-free antiviral therapy in kidney transplant recipients with chronic hepatitis c
    Approximately 5 to 15% of kidney transplant (KT) recipients have chronic hepatitis C. Hepatitis C virus (HCV) infection is associated to an increased risk of mortality in these patients as a consequence of liver disease, higher infection rates and cardiovascular disease [1]. Moreover, HCV infection in KT patients is an independent risk factor for graft loss, and it is associated with proteinuria, chronic rejection, transplant glomerulopathy, post-transplant diabetes and HCV-associated glomerulo-nephritis [2,3].


    Date de mise en ligne : Samedi 24 décembre 2016
    Xin Yu, Peixiang Lan, Xuben Hou, Qiuju Han, Nan Lu, Tao Li, Chenwei Jiao, Jian Zhang, Cai Zhang, Zhigang Tian
    HBV Inhibits LPS-induced NLRP3 Inflammasome Activation and IL-1β Production via Suppressing NF-κB Pathway and ROS Production
    Hepatitis B virus (HBV), an enveloped DNA virus that belongs to the Hepadnaviridae family, chronically infects more than 400 million people worldwide. Its persistence is a major cause of liver cirrhosis and hepatocellular carcinoma (HCC). HBV has been considered to be a “stealth virus” that induces negligible innate immune responses during the early phase of infection. Viral proteins (HBV polymerase, HBx, HBeAg and HBsAg), can inhibit distinct innate immune pathways, leading to immunosuppression and viral persistence [1,2].


    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
    Heng Wu, Tianpeng Zhang, Fei Pan, Clifford J. Steer, Zhuoyu Li, Xin Chen, Guisheng Song
    MicroRNA-206 prevents hepatosteatosis and hyperglycemia by facilitating insulin signaling and impairing lipogenesis
    Results from the American Heart Association showed that nearly 73% of U.S adults are overweight or obese. Obesity and its associated co-morbidities are among the most prevalent and challenging conditions confronting the medical profession in the past century. A major metabolic consequence of obesity is insulin resistance, which is a major risk factor of type 2 diabetes (T2D) and NAFLD [1]. NAFLD is the accumulation of excessive amounts of lipids within hepatocytes that is not caused by alcohol. It is estimated that 90% of obese patients have some form of fatty liver, ranging from hepatosteatosis to more severe forms of NASH (non-alcoholic steatohepatitis), which can give rise to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) [2].


    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 that is characterized by upregulation of costimulatory 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 : Jeudi 22 décembre 2016
    Ranka Vukotic, Fabio Conti, Pietro Andreone
    Hepatitis C virus eradication in the elderly: The challenge worth a long-life elixir?
    Senectus enim insanabilis morbus est.Lucius Annaeus Seneca, c. 65 AD.


    Date de mise en ligne : Jeudi 22 décembre 2016
    Stefano Caruso, Julien Calderaro, Eric Letouzé, Jean-Charles Nault, Gabrielle Couchy, Anaïs Boulai, Alain Luciani, Elie-Serge Zafrani, Paulette Bioulac-Sage, Olivier Seror, Sandrine Imbeaud, Jessica Zucman-Rossi
    Germline and somatic DICER1 mutations in familial and sporadic liver tumors
    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide and is related to different risk factors, including chronic hepatitis B (HBV) and C (HCV) virus infection, alcohol abuse, metabolic syndrome and other genetic disorders [1]. Only few studies reported familial clusters of HCC and most of them were described in areas with endemic HBV infection suggesting that the viral infection could participate to the familial aggregation of HCC [2–10]. However, growing evidence suggests that a family history of liver cancer significantly increases HCC risk, and a multifactorial inheritance could contribute to increasing this risk, regardless of viral hepatitis infection [11–13].


    Date de mise en ligne : Mercredi 21 décembre 2016
    Antje Mohs, Nadine Kuttkat, Johanna Reißing, Henning Wolfgang Zimmermann, Roland Sonntag, Amanda Proudfoot, Sameh A. Youssef, Alain de Bruin, Francisco Javier Cubero, Christian Trautwein
    Functional role of CCL5/RANTES for HCC progression during chronic liver disease
    Under physiological conditions the inflammatory response is a beneficial process to restore tissue injury and to protect against pathogenic causes. However, persistent liver damage triggers chronic inflammation leading to scar formation and enhances the susceptibility for cancer development [1]. Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death and the fifth most common solid tumor worldwide [2]. Most HCCs develop in the context of chronic liver inflammation [3–5].


    Date de mise en ligne : Mercredi 21 décembre 2016
    Martin F. Sprinzl, Peter R. Galle
    Current progress in immunotherapy of hepatocellular carcinoma
    During the last years, new immune-modulatory agents were introduced for oncological treatment, eventually leading to the clinical breakthrough of checkpoint inhibitors (CPI) targeting cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1) and programmed death-1 ligand (PD-1L) [1–5]. Under physiological conditions these molecules resolve T cell activation to maintain inflammatory homeostasis, protect tissue integrity and prevent unwanted auto-immunity [6]. CPI administration in tumor patients, however, unleashes tumor-directed cytotoxic T cells specific against an unknown spectrum of tumor-associated antigens (TAA).


    Date de mise en ligne : Vendredi 16 décembre 2016
    Philipp Schwabl, Eva Hambruch, Berit A. Seeland, Hubert Hayden, Michael Wagner, Lukas Garnys, Bastian Strobel, Tim-Lukas Schubert, Florian Riedl, Dieter Mittereger, Michael Burnet, Patrick Starlinger, Georg Oberhuber, Ulrich Deuschle, Nataliya Rohr-Udilova, Bruno K. Podesser, Markus Peck-Radosavljevic, Thomas Reiberger, Claus Kremoser, Michael Trauner
    The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction
    Patients with chronic liver disease ultimately develop cirrhosis and portal hypertension (PHT) [1] if the underlying etiology cannot be effectively treated [2]. Most severe complications occur in patients with advanced intrahepatic collagen deposition [3,4] and pronounced PHT [5]. PHT is primarily caused by increased intrahepatic vascular resistance that results from both structural remodelling (fibrogenesis and scarring) and functional alterations (contractile hepatic stellate cells and endothelial dysfunction).


    Date de mise en ligne : Jeudi 15 décembre 2016
    Hung-Tsung Wu, Feng-Hwa Lu, Horng-Yih Ou, Yu-Chu Su, Hao-Chang Hung, Jin-Shang Wu, Yi-Ching Yang, Chao-Liang Wu, Chih-Jen Chang
    Corrigendum to “The role of hepassocin in the development of non-alcoholic fatty liver disease”
    We would like to highlight typographical errors in the above manuscript. The text (page 1067, Results Section) should read “NAFLD subjects had a significantly higher serum HPS level than those without it (7699.7±194.9 vs. 6112.3±143.7pg/ml; p<0.001) (Fig. 1A).” Similarly, the same typographical error also appears in Fig. 1A, and the unit should be corrected as μg/ml (page 1068). These are typographical errors that were not noted during the review process. We would like to apologize to the readers for any inconvenience or misunderstanding, which may have occurred as a result.


    Date de mise en ligne : Jeudi 15 décembre 2016
    Vicente Arroyo, Richard Moreau
    Diagnosis and prognosis of acute on chronic liver failure (ACLF) in cirrhosis
    Acute-on-chronic liver failure (ALCF) is characterized by three major features:


    Date de mise en ligne : Lundi 12 décembre 2016
    Anna K. Kopec, Nikita Joshi, Holly Cline-Fedewa, Anna V. Wojcicki, Jessica L. Ray, Bradley P. Sullivan, John E. Froehlich, Brendan F. Johnson, Matthew J. Flick, James P. Luyendyk
    Fibri(nogen) drives repair after acetaminophen-induced liver injury via leukocyte αMβ2 integrin-dependent upregulation of MMP12
    Acute liver injury caused by acetaminophen (APAP) overdose in experimental animals is associated with activation of the coagulation cascade. Strong evidence also connects APAP-induced liver injury in humans to changes in the hemostatic system including thrombocytopenia, elevated plasma levels of thrombin-antithrombin (TAT), increased levels of procoagulant microvesicles, and a reduction in plasma fibrinogen concentration [1–3]. Prolongation of the prothrombin time-international normalized ratio (PT-INR) is linked with increased morbidity in patients with acute liver failure whereas preservation of plasma fibrinogen is coupled to improved outcome [2,4–6].


    Date de mise en ligne : Lundi 12 décembre 2016
    Alessandra Mangia, Simone Susser, Valeria Piazzolla, Ernesto Agostinacchio, Giulio De Stefano, Vincenzo Palmieri, Giancarlo Spinzi, Immacolata Carraturo, Domenico Potenza, Ruggero Losappio, Andrea Arleo, Maria Miscio, Rosanna Santoro, Christoph Sarrazin, Massimiliano Copetti
    Sofosbuvir and Ribavirin for genotype 2 HCV infected patients with cirrhosis: a real life experience
    HCV genotype still represents the most important viral factor for selection of appropriate Direct Antiviral Agents (DAA) regimen and duration in chronic HCV infection. In the era of Interferon-based therapies, genotype 2 (GT2) was considered easy to treat. Indeed, the first interferon free treatment, based on the combination of Sofosbuvir (SOF) 400 mg + Ribavirin (RBV) 1000-1200 mg daily, was investigated in patients infected with this genotype and until very recently [1] has represented the standard of care [2].


    Date de mise en ligne : Lundi 12 décembre 2016
    Eloi R. Verrier, Catherine Schuster, Thomas F. Baumert
    Advancing hepatitis B virus entry inhibitors
    Despite the effective antivirals and vaccines, chronic hepatitis B virus (HBV) infection remains a major public health problem worldwide [1,2]. Due to limited access, late or absent detection and vertical transmission, the prevalence of HBV infection is estimated to be 250–350 million infected individuals [1,3]. HBV infection is a leading cause of hepatocellular carcinoma worldwide. While current therapies, based on pegylated-interferon and nucleos(t)ide analogs effectively decrease viral load, viral elimination is rare.


    Date de mise en ligne : Lundi 12 décembre 2016
    Dorothee Schwinge, Franziska von Haxthausen, Alexander Quaas, Antonella Carambia, Benjamin Otto, Fabian Glaser, Benedikt Höh, Nina Thiele, Tanja Schoknecht, Samuel Huber, Niklas Steffens, Ansgar W. Lohse, Johannes Herkel, Christoph Schramm
    Dysfunction of hepatic regulatory T cells in experimental sclerosing cholangitis is related with IL-12 signaling
    Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease leading to fibrosis and obliteration of bile ducts, and eventually to liver cirrhosis [1]. In addition to liver disease, 60–80% of PSC patients have a history of associated inflammatory bowel disease (IBD) [2,3]. There is currently no medical treatment available with a proven effect on disease progression, making PSC a major indication for liver transplantation [4]. The etiology of PSC is still unknown, but immune dysregulation is considered to be part of PSC pathogenesis[5].


    Date de mise en ligne : Lundi 12 décembre 2016
    Yi Ni, Stephan Urban
    Stem cell-derived hepatocytes: A promising novel tool to study hepatitis B virus infection
    Hepatitis B virus (HBV) infection affects 240 million people worldwide. HBV is the major cause for progressive liver diseases often leading to cirrhosis and hepatocellular carcinoma. After the isolation and genetic characterization of HBV, it became instantly clear that the virus essentially depends on species- and hepatocyte-specific host factors in its replication cycle [1]. Although hepatoma-derived cell lines support HBV replication and particle assembly following transfection of cloned viral genomes [2], only primary hepatocytes from humans (PHH) [3] or a tree shrew [4] support the full viral replication cycle.


    Date de mise en ligne : Lundi 12 décembre 2016
    Philippe Kolly, Jean-François Dufour
    Patients with hepatocellular carcinoma: Your address matters!
    One of the major goals of research on hepatocellular carcinoma (HCC) is to improve overall survival (OS), either by exploring new therapeutic options, improving patient selection for various treatment strategies, or enhancing early detection of HCC. The emergence of systemic therapies has contributed to the increase in OS of patients with advanced HCC since 2007, with evidence provided by the SHARP trial [1] and, very recently, by the RESORCE trial [2]. The European guidelines for the management of HCC suggest that patients at risk of HCC should be included in a surveillance program [3].


    Date de mise en ligne : Lundi 12 décembre 2016
    Yuanjun Shen, Bingfang Yan
    Covalent inhibition of carboxylesterase-2 by sofosbuvir and its effect on the hydrolytic activation of tenofovir disoproxil
    Sofosbuvir is considered as a paradigm shift in treating hepatitis C viral infection (HCV) [1]. Patients co-infected with human immunodeficiency virus (HIV) usually receive both anti-HCV and antiretroviral therapy [2]. Emerging evidence, recently reported by this and other journals, has linked sofosbuvir-containing regimens to liver or kidney toxicity when co-administered with anti-HIV drugs [2–6]. Interestingly, sofosbuvir and some anti-HIV drugs such as tenofovir disoproxil contain ester and/or amide bonds.


    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
    Nonalcoholic fatty liver disease (NAFLD) covers a broad spectrum of liver abnormalities ranging from simple steatosis to nonalcoholic 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 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 : Lundi 05 décembre 2016
    Hyun-seok Kim, Adaugo Ike, Justin Mathew
    Effect of exercise on the development of new fatty liver and the resolution of existing fatty liver
    We have read and are greatly intrigued by the article in a recent issue, written by Sung et al., showing evidence that there is a dose-dependent association between the amount of exercise with incidence and resolution of non-alcoholic fatty liver disease (NAFLD) [1]. The authors concluded that any amount of exercise was associated with a significant benefit for both a decrease in the incidence of new fatty liver and for improvement of existing fatty liver. This finding is supported by previous studies that suggest weight loss through exercise provides benefits in prevention and improvement in NAFLD [2,3].


    Date de mise en ligne : Samedi 03 décembre 2016
    David Wyles, Hadas Dvory-Sobol, Evguenia S. Svarovskaia, Brian P. Doehle, Ross Martin, Nezam H. Afdhal, Kris V. Kowdley, Eric Lawitz, Diana M. Brainard, Michael D. Miller, Hongmei Mo, Edward J. Gane
    Post-treatment resistance analysis of hepatitis C virus from phase II and III clinical trials of ledipasvir/sofosbuvir
    In recent years, direct-acting antiviral drugs (DAAs) developed for the treatment of hepatitis C virus (HCV) have replaced the previous standard of care of pegylated interferon and ribavirin. Inhibitors targeting the viral NS3/4A protease (telaprevir, boceprevir, simeprevir, paritaprevir and grazoprevir), NS5B polymerase (the nucleotide inhibitor sofosbuvir and the non-nucleoside inhibitor dasabuvir), and NS5A protein (ledipasvir, daclatasvir, ombitasvir and elbasvir) have been approved by the USA FDA, with more in late-phase clinical trials.


    Date de mise en ligne : Samedi 03 décembre 2016
    Sara Montagnese, Michele De Rui, Paolo Angeli, Piero Amodio
    Neuropsychiatric Performance in Patients with Cirrhosis: Who is “Normal”?
    Normal neuropsychiatric performance in cirrhosis has been traditionally defined by the absence of any degree of hepatic encephalopathy (HE) and/or the absence of psychometric or neurophysiological abnormalities, by comparison with reference data from the healthy population. It is our impression that as our understanding and management of end-stage liver disease continues to change, the concept of normal neuropsychiatric performance may also need updating. This review explores novel and possibly more pragmatic interpretations of neuropsychiatric “normality” by comparison with top personal performance, in terms of risk of overt HE/brain failure and in relation with events such as liver transplantation, decompensation, acute-on-chronic liver failure (ACLF) and Transjugular Intrahepatic Portal-systemic Shunt (TIPS) placement.


    Date de mise en ligne : Mercredi 30 novembre 2016
    Valentin Le Guen, Jean-Paul Judor, Françoise Boeffard, Vanessa Gauttier, Nicolas Ferry, Jean-Paul Soulillou, Sophie Brouard, Sophie Conchon
    Alloantigen gene transfer to hepatocytes promotes tolerance to pancreatic islet graft by inducing CD8+ regulatory T cells
    Allogeneic transplantation remains the only treatment available for end-stage diseases of various organs, such as kidney, heart, liver, and pancreas. However, the donor-specific allogeneic immune response of the host requires life-long immunosuppression. Despite constant progress, these long-term treatments still carry serious side effects, from toxicity to increased risk of opportunistic infections and of neoplasia [1,2]. An ideal alternative to the need for long-term exposure to immunosuppressors would consist of the induction of a donor-specific immune tolerance, which, despite having been achieved experimentally, remains a challenge in the clinical arena.


    Date de mise en ligne : Mercredi 30 novembre 2016
    Deepak Joshi, Nitika Gupta, Marianne Samyn, Maesha Deheragoda, Fabienne Dobbels, Michael A. Heneghan
    The management of childhood liver diseases in adulthood
    An increasing number of patients with childhood liver disease survive into adulthood. These young adults are now entering adult services and require ongoing management. Aetiologies can be divided into liver diseases that develop in young adults which present to adult hepatologists i.e., biliary atresia and Alagille syndrome or liver diseases that occur in children/adolescents and adults i.e., autoimmune hepatitis or Wilson’s disease. To successfully manage these young adults, a dynamic and responsive transition service is essential.


    Date de mise en ligne : Mardi 29 novembre 2016
    Benjamin L. Woolbright, Hartmut Jaeschke
    Role of the Inflammasome in Acetaminophen-induced Liver Injury and Acute Liver Failure
    Drug-induced acute liver failure carries a high morbidity and mortality rate. Acetaminophen overdose is the number one cause of acute liver failure and remains a major problem in Western medicine. Administration of N-acetyl cysteine is an effective antidote when given before the initial rise in toxicity; however, many patients present to the hospital after this stage occurs. As such, treatments which can alleviate late-stage acetaminophen-induced acute liver failure are imperative. While the initial mechanisms of toxicity are well described, a debate has occurred recently in the literature over whether or not there exists a second phase of injury, mediated by inflammatory processes.


    Date de mise en ligne : Mardi 29 novembre 2016
    S Pischke, J Hartl, SD Pas, AW Lohse, BC Jacobs, AA 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, thyreoiditis 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 : Mardi 29 novembre 2016
    Katalin Dezső, András Rókusz, Edina Bugyik, Armanda Szücs, András Szuák, Bence Dorogi, Mátyás Kiss, Ágnes Nemeskéri, Péter Nagy, Sándor Paku
    Human liver regeneration in advanced cirrhosis is organized by the portal tree
    Cirrhosis is the final common outcome of all chronic liver diseases, resulting in patients’ suffering and a tremendous burden for health care systems [1]. It is characterized by the diffuse nodular transformation of the liver tissue and the deposition of collagen rich extracellular matrix. There are several in vivo experimental models for hepatic fibrosis/cirrhosis and the progression of the disease is well documented in human livers as well, thus the evolution of cirrhosis looks to be a well characterized straightforward process.


    Date de mise en ligne : Lundi 28 novembre 2016
    Eirini Kyrana, Anil Dhawan
    Minimal hepatic encephalopathy in children, uncommon or unrecognised? Time to act
    Hepatic encephalopathy has been defined as a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction after exclusion of an intrinsic brain disease [1]. Minimal hepatic encephalopathy (MHE) has been used to describe a subset of patients with the mildest form of encephalopathy, not detected on clinical examination, but detected on psychometric testing [1,2]. The term applies to both patients with cirrhosis and patients with portosystemic shunts without intrinsic liver disease such as isolated portal vein thrombosis [1].


    Date de mise en ligne : Lundi 28 novembre 2016
    Mirjana Ziemer, Eleni Koukoulioti, Susanne Beyer, Jan C. Simon, Thomas Berg
    Managing immune checkpoint-inhibitor-induced severe autoimmune-like hepatitis by liver-directed topical steroids
    Immuno-oncology therapies are being increasingly used as a principle pharmacological cancer treatment. The CTLA4-antibody ipilimumab, and PD-1-antibodies pembrolizumab and nivolumab have revolutionized anti-neoplastic therapies [1–3]. They are licensed to treat for advanced melanoma, non-small-lung cancer and renal cell carcinoma, but are currently being evaluated in a broad spectrum of malignant diseases including hepatocellular carcinoma [4,5]. However, due to their mode of action, the blockade of T cell inhibition, these new class of drugs have a spectrum of adverse reactions, specifically the induction of autoimmune-like diseases [6,7].


    Date de mise en ligne : Samedi 26 novembre 2016
    Andrea Notarpaolo, Richard Layese, Paolo Magistri, Maria Gambato, Michele Colledan, Giulia Magini, Lucia Miglioresi, Alessandro Vitale, Giovanni Vennarecci, Cecilia D Ambrosio, Patrizia Burra, Fabrizio Di Benedetto, Stefano Fagiuoli, Marco Colasanti, Giuseppe Maria Ettorre, Arnoldo Andreoli, Umberto Cillo, Alexis Laurent, Sandrine Katsahian, Etienne Audureau, Françoise Roudot-Thoraval, Christophe Duvoux
    Validation of the AFP model as a predictor of HCC recurrence in patients with viral hepatitis-related cirrhosis who had received a liver transplant for HCC
    Liver transplantation (LT) is considered the best treatment of hepatocellular carcinoma (HCC). However, its efficacy is limited by the risk of tumor recurrence, which results in rapid death and graft loss in patients who are not selected appropriately, making LT futile.


    Date de mise en ligne : Vendredi 25 novembre 2016
    Carolin Lackner, Walter Spindelboeck, Johannes Haybaeck, Philipp Douschan, Florian Rainer, Luigi Terracciano, Josef Haas, Andrea Berghold, Ramon Bataller, Rudolf E. Stauber
    Histological parameters and alcohol abstinence determine long-term prognosis in patients with alcoholic liver disease
    Alcoholic liver disease (ALD) is a substantial burden on public health and is responsible for half of the cases of cirrhosis worldwide [1,2]. Despite its health and socioeconomic burden, there have not been major advances in the management of these patients. There are no widespread programs for early detection and the current therapy for its more severe form (i.e., prednisolone for alcoholic hepatitis) has not evolved since 1971 [3,4]. The complex pathogenesis of ALD, influenced by host and environmental factors, is only partially understood.


    Date de mise en ligne : Jeudi 24 novembre 2016
    Hidenori Toyoda, Takashi Kumada, Toshifumi Tada, Noritomo Shimada, Koichi Takaguchi, Tomonori Senoh, Kunihiko Tsuji, Yoshihiko Tachi, Atsushi Hiraoka, Toru Ishikawa, Toshihide Shima, Takeshi Okanoue
    Efficacy and tolerability of an IFN-free regimen with DCV/ASV for elderly patients infected with HCV genotype 1B
    Chronic hepatitis C virus (HCV) infection is a major cause of cirrhosis and hepatocellular carcinoma (HCC). The risk of these complications is reduced by the eradication of HCV using antiviral therapy, i.e., sustained virologic response (SVR) [1]. Interferon (IFN)-based therapies, usually in combination with ribavirin, have been administered to eradicate HCV. However, it is often difficult for aged patients to undergo these treatments due to the adverse effects of IFN and ribavirin [2–4].


    Date de mise en ligne : Jeudi 24 novembre 2016
    David J. Pinato, Clarence Yen, Rohini Sharma
    Reply to: ‘Validating the ALBI grade: Its current and future use in HCC prognostication’
    We thank Chan et al. for their kind comments outlined in their Letter to the Editor. A number of points are also highlighted for discussion pertaining to our manuscript “The ALBI grade provides objective hepatic reserve estimation across each BCLC stage of hepatocellular carcinoma” [1].


    Date de mise en ligne : Jeudi 24 novembre 2016
    Satomi Shimura, Koichi Watashi, Kento Fukano, Michael Peel, Ann Sluder, Fumihiro Kawai, Masashi Iwamoto, Senko Tsukuda, Junko S. Takeuchi, Takeshi Miyake, Masaya Sugiyama, Yuki Ogasawara, Sam-Yong Park, Yasuhito Tanaka, Hiroyuki Kusuhara, Masashi Mizokami, Camille Sureau, Takaji Wakita
    Cyclosporin derivatives inhibit hepatitis B virus entry without interfering with NTCP transporter activity
    Hepatitis B virus (HBV) infection is a worldwide public health problem, which is estimated to chronically infect approximately 240 million individuals [1,2]. Chronic HBV infection elevates the risk of developing liver cirrhosis and hepatocellular carcinoma [3–5]. Current clinical treatments for HBV infection include interferons (IFN)s and nucleos(t)ide analogs (NAs) [6–8]. IFNα and its pegylated form (PegIFNα) modulate host immune response to viral infection and directly inhibit HBV replication in hepatocytes.


    Date de mise en ligne : Jeudi 24 novembre 2016
    Gladys Ferrere, Laura Wrzosek, Frédéric Cailleux, Williams Turpin, Virginie Puchois, Madeleine Spatz, Dragos Ciocan, Dominique Rainteau, Lydie Humbert, Cindy Hugot, Françoise Gaudin, Marie-Louise Noordine, Véronique Robert, Dominique Berrebi, Muriel Thomas, Sylvie Naveau, Gabriel Perlemuter, Anne-Marie Cassard
    Fecal microbiota manipulation prevents dysbiosis and alcohol-induced liver injury in mice
    Chronic alcohol consumption is the major cause of chronic liver disease in the world. Most long-term heavy drinkers develop steatosis, but only 10–35% develop liver inflammation (hepatitis), of which 8–20% ultimately progresses to cirrhosis [1]. Thus, factors other than alcohol intake influence the onset and progression of alcoholic liver disease (ALD). Among these, the intestinal microbiota (IM) plays a role in the pathogenesis of ALD [2,3]. The IM is involved in host homeostasis and maintenance of the intestinal barrier by several mechanisms such as preventing colonization by pathogenic bacteria and by cooperating with the intestinal epithelium to produce mucin 2 [3–6].


    Date de mise en ligne : Jeudi 24 novembre 2016
    Anthony W.H. Chan, Howard H.W. Leung, Charing C.N. Chong, Stephen L. Chan
    Validating the ALBI grade: Its current and future use in HCC prognostication
    We have read with interest the article from Pinato et al., who validated the prognostication of the albumin-bilirubin (ALBI) grade in an international cohort of 2426 patients with hepatocellular carcinoma (HCC) from Europe, the United States and Asia [1]. The authors confirmed that the ALBI grade was an independent prognostic factor among different treatment modalities, geographical location and time of study recruitment across each Barcelona Clinic Liver Cancer (BCLC) stage. In this letter, we would like to raise two interesting points for discussion.


    Date de mise en ligne : Lundi 21 novembre 2016
    Margaret Hellard, Alisa Pedrana, Nick Scott
    Targeted direct-acting antiviral treatment for chronic hepatitis C: A financial reality or an obstacle to elimination?
    In the article “Are targeted treatment recommendations in chronic hepatitis C tailored to diagnostic methods of fibrosis?” Deuffic-Burban et al. examined different policy scenarios for giving individuals with chronic hepatitis C infection access to direct-acting antiviral (DAA) treatments. The authors used a Markov model to estimate the 5-year reduction in the incidence of cirrhosis, liver complications and liver deaths compared to no treatment under three different rules for access: providing therapy only to patients with ⩾F3 fibrosis scores, providing therapy only to patients with ⩾severe F2 fibrosis scores, and providing universal therapy.


    Date de mise en ligne : Lundi 21 novembre 2016
    Maria J. Monte, Marta Alonso-Peña, Oscar Briz, Elisa Herraez, Carmen Berasain, Josepmaria Argemi, Jesus Prieto, Jose J.G. Marin
    ACOX2 deficiency: An inborn error of bile acid synthesis identified in an adolescent with persistent hypertransaminasemia
    Bile acids play essential digestive functions and are critical signaling molecules that modulate intermediate metabolism and liver tissue homeostasis. They are synthetized by hepatocytes from cholesterol [1,2] through two main pathways involving enzymes located at the endoplasmic reticulum, cytosol, mitochondria and peroxisomes. These enzymes are responsible for modifying the sterol nucleus of cholesterol and shortening its side-chain [3,4]. Inborn errors of bile acid synthesis are rare autosomal recessive diseases accounting for 1–2% of cholestatic disorders in children [5].


    Date de mise en ligne : Vendredi 18 novembre 2016
    Teresa Ramirez, Yong-Mei Li, Shi Yin, Ming-Jiang Xu, Dechun Feng, Zhou Zhou, Mengwei Zang, Partha Mukhopadhyay, Zoltan V. Varga, Pal Pacher, Bin Gao, Hua Wang
    Aging aggravates alcoholic liver injury and fibrosis in mice by downregulating sirtuin 1 expression
    Alcoholic liver disease (ALD) is considered to be a major cause of morbidity and mortality nationwide [1–5]. It has an array of liver pathology that ranges from simple fatty liver to more severe forms of liver injury such as steatohepatitis, cirrhosis, and hepatocellular carcinoma. Many factors have been shown to affect the development and progression of ALD, including age, gender, ethnicity, genetic factors, drinking pattern, type of alcohol consumed, dose, duration, obesity, viral hepatitis infection, and environment [1–5].


    Date de mise en ligne : Jeudi 17 novembre 2016
    Elisabetta Ceni, Tommaso Mello, Simone Polvani, Mireille Vasseur-Cognet, Mirko Tarocchi, Sara Tempesti, Duccio Cavalieri, Luca Beltrame, Giada Marroncini, Massimo Pinzani, Stefano Milani, Andrea Galli
    The orphan nuclear receptor COUP-TFII coordinates hypoxia-independent proangiogenic responses in hepatic stellate cells
    An exuberant wound healing response to chronic liver injury culminates in excessive and altered deposition of extracellular matrix (ECM) components. It is temporally and spatially linked with vascular remodelling of hepatic sinusoids, angiogenesis and recruitment of inflammatory cells [1]. Hepatic stellate cells (HSC) play an important role in the physiological homeostasis of ECM in the liver, and are the precursors of activated myofibroblast-like cells responsible for the development of liver fibrosis.


    Date de mise en ligne : Mardi 15 novembre 2016
    Thomas Reiberger, Mattias Mandorfer
    Beta adrenergic blockade and decompensated cirrhosis
    Non-selective betablockers (NSBBs) remain the cornerstone of medical treatment of portal hypertension. The evidence for their efficacy to prevent variceal bleeding is derived from prospective trials, which largely excluded patients with refractory ascites and renal failure. In parallel to the increasing knowledge on portal hypertension-induced changes in systemic hemodynamics, cardiac function, and renal perfusion, emerging studies have raised concerns about harmful effects of NSBBs. Clinicians are facing an ongoing controversy on the use of NSBBs in patients with advanced cirrhosis.


    Date de mise en ligne : Lundi 14 novembre 2016
    Jorge Fonseca, Gonçalo Nunes, Cristina Fonseca, Manuela Canhoto, Ana Teresa Barata, Carla Adriana Santos
    Comment to: “EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease”
    We had received with great interest the new Clinical Practice Guidelines on NAFLD, a joint consensus from the European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO) and the paper fulfilled our expectations. Every clinician taking care of liver patients is well aware of the increasing NAFLD epidemic and, also, the importance of the obesity/insulin resistance/diabetes burden growing in Western societies [1].


    Date de mise en ligne : Lundi 14 novembre 2016
    Giulio Marchesini, Michael Roden, Roberto Vettor
    Response to: Comment to “EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease”
    We thank Jorge Fonseca et al. for their comments, which give us the opportunity to clarify the controversial issue of dietary approach to NAFLD, an issue that did not receive adequate attention in the Clinical Practice Guidelines (CPG) due to space constraints. They are concerned about the sentence suggesting “low-to-moderate fat and moderate-to-high carbohydrate intake” as a reasonable option for NAFLD cases. Indeed, no recommendation on nutrient composition of the diet was issued within the CPG, but a formal recommendation reads “Dietary recommendations should consider energy restriction and exclusion of NAFLD-promoting components (processed food, and food and beverages high in added fructose).


    Date de mise en ligne : Jeudi 10 novembre 2016
    Pei-Chien Tsai, Chung-Feng Huang, Ming-Lung Yu
    Unexpected early tumor recurrence in patients with hepatitis C virus-related hepatocellular carcinoma undergoing interferon-free therapy: Issue of the interval between HCC treatment and antiviral therapy
    We read with great interest the report by Reig et al. published in a recent issue of the Journal of Hepatology [1]. Reig et al. observed an unexpected high rate of early recurrence of hepatocellular carcinoma (HCC) after interferon-free direct-acting antiviral (DAA) therapy in patients with hepatitis C virus (HCV)-related HCC post curative therapy. In our previous cohort of 105 HCV patients with post curative HCC therapies, we also observed a high rate of HCC recurrence (22.9%) early after PegIFN plus ribavirin therapy (within 6months after end of antiviral therapy) [2].


    Date de mise en ligne : Samedi 05 novembre 2016
    Jie Wang, Man Du, Hongxin Huang, Ran Chen, Junqi Niu, Jianning Jiang, Hui Zhuang, Fengmin Lu
    Reply to: “Serum HBV pgRNA as a clinical marker for cccDNA activity”
    We appreciate the comments from Giersch et al. on our study on the nature and origin of serum HBV RNA and its association with the persistence of viral infection and rebound [1]. The data from Giersch et al. supports our speculation that the detection of serum HBV RNA may reflect the activity of intrahepatic covalently closed circular DNA (cccDNA) [2].


    Date de mise en ligne : Samedi 05 novembre 2016
    Veronika Lukacs-Kornek, Frank Lammert
    The progenitor cell dilemma: Cellular and functional heterogeneity in assistance or escalation of liver injury
    Liver progenitor cells (LPCs) are quiescent cells that are activated during liver injury and thought to give rise to hepatocytes and cholangiocytes in order to support liver regeneration and tissue restitution. While hepatocytes are capable of self-renewal, during most chronic injuries the proliferative capacity of hepatocytes is inhibited, thus LPCs provide main source for regeneration. Despite extensive lineage tracing studies, their role and involvement in these processes are often controversial.


    Date de mise en ligne : Samedi 05 novembre 2016
    Carlo Spirli, Valeria Mariotti, Ambra Villani, Luca Fabris, Romina Fiorotto, Mario Strazzabosco
    Adenylyl cyclase 5 links changes in calcium homeostasis to cAMP-dependent cyst growth in polycystic liver disease
    Autosomal dominant polycystic kidney disease (ADPKD) is characterized by formation of multiple cysts in the kidney, liver and pancreas [1]. In the liver (polycystic liver disease [PLD]-ADPKD), multiple fluid-filled cysts progressively dilate and grow until their complications mandate surgery or liver transplantation [2,3]. PLD-ADPKD is associated with mutations in one of two genes: PKD1, and PKD2, that code for polycystin-1 (PC1) and polycystin-2 (PC2), respectively. These two proteins are involved in intracellular signaling, cell differentiation and epithelial morphogenesis [4].


    Date de mise en ligne : Samedi 05 novembre 2016
    Vincent Mallet, Kamal Hamed, Michaël Schwarzinger
    Prognosis of patients with chronic hepatitis B in France (2008–2013): A nationwide, observational and hospital-based study
    Approximately 3.61% of the global population is chronically infected with hepatitis B virus (HBV) [1]. A fraction of these will progress to a liver-related complication, including end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC), and will contribute to more than half of liver deaths worldwide [2,3].


    Date de mise en ligne : Samedi 05 novembre 2016
    Katja Giersch, Lena Allweiss, Tassilo Volz, Maura Dandri, Marc Lütgehetmann
    Serum HBV pgRNA as a clinical marker for cccDNA activity
    With great interest, we read the manuscript “Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound” by Wang et al. published in the Journal of Hepatology [1]. The authors confirmed the recent observation that in addition to hepatitis B virus (HBV) DNA, HBV RNA is present in the serum of chronically HBV-infected patients [2–4] and revealed that this HBV RNA is the virus pregenomic RNA (pgRNA) encapsidated and enveloped in virus-like particles.


    Date de mise en ligne : Samedi 05 novembre 2016
    Salvador Augustin, Mónica Pons, Joan Genesca
    Validating the Baveno VI recommendations for screening varices
    We read with great interest the recent article by Maurice et al. [1], in which they essentially confirm the validity of the recent Baveno VI recommendations regarding the use of transient elastography and platelet count for the screening and surveillance of gastroesophageal varices in patients with compensated advanced chronic liver disease (cACLD) [2]. Based on preliminary information from a few studies [3], the Baveno VI recommendations indicated that in patients with cACLD a liver stiffness measurement <20kPa and a platelet count >150,000cells/μl have a very low risk of having varices needing treatment (large varices) and consequently can avoid screening endoscopy [2].


    Date de mise en ligne : Jeudi 03 novembre 2016
    Naveed Z. Janjua, Mei Chong, Margot Kuo, Ryan Woods, Jason Wong, Eric M. Yoshida, Morris Sherman, Zahid A. Butt, Hasina Samji, Darrel Cook, Amanda Yu, Maria Alvarez, Mark Tyndall, Mel Krajden
    Long-term effect of sustained virological response on hepatocellular carcinoma in patients with hepatitis C in Canada
    Hepatitis C virus (HCV) infection is a major global health concern with about 184 million people infected worldwide [1]. In North America, about two-thirds of chronic infections are among people born between 1945–1965 and, having acquired the virus decades ago, are now increasingly being diagnosed with serious liver-related illnesses including decompensated cirrhosis and hepatocellular carcinoma (HCC) [2–4]. Due to the low uptake and effectiveness (∼50% cured), interferon-based treatments resulted in limited population level impact [5,6].


    Date de mise en ligne : Mercredi 02 novembre 2016
    Austin G. Duffy, Susanna V. Ulahannan, Oxana Makorova-Rusher, Osama Rahma, Heiner Wedemeyer, Drew Pratt, Jeremy L. Davis, Marybeth S. Hughes, Theo Heller, Mei ElGindi, Ashish Uppala, Firouzeh Korangy, David E. Kleiner, William D. Figg, David Venzon, Seth M. Steinberg, Aradhana M. Venkatesan, Venkatesh Krishnasamy, Nadine Abi-Jaoudeh, Elliot Levy, Brad J. Wood, Tim F. Greten
    Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma
    Hepatocellular carcinoma (HCC) is one of the most frequently occurring cancers worldwide, ranked 3rd in global incidence by the International Agency for Research on Cancer [1]. HCC typically occurs in the setting of chronic inflammation, such as that induced by viral hepatitis. In contrast to other types of cancer, where surgery, radiation and chemotherapies dominate the therapeutic landscape, in HCC locoregional treatments are widely applied, either with curative (ablative procedures, surgery) or palliative (arterial chemoembolization) intent [2].


    Date de mise en ligne : Mercredi 02 novembre 2016
    Oluwaseun Falade-Nwulia, Mark Sulkowski
    The HCV care continuum does not end with cure: A call to arms for the prevention of reinfection
    After the approval of safe and highly effective oral direct acting agents (DAA) for the treatment of hepatitis C virus (HCV) in 2014, commentaries and discussions about the elimination of hepatitis C on a population level have rapidly proliferated in scientific literature and popular press. Indeed, the World Health Organization (WHO) has announced proposed global targets of an 80% reduction in new cases of HCV infection from the 2010 level and several countries, including Australia, Egypt, Georgia and Iceland have embarked on ambitious plans to control HCV infection in their populations [1].


    Date de mise en ligne : Mardi 01 novembre 2016
    Anshu Srivastava, Saurabh Chaturvedi, Rakesh Kumar Gupta, Rohan Malik, Amrita Mathias, Naranamangalam R. Jagannathan, Sunil Jain, Chandra Mani Pandey, Surender Kumar Yachha, Ram Kishor Singh Rathore
    Minimal hepatic encephalopathy in children with chronic liver disease: Prevalence, pathogenesis and magnetic resonance-based diagnosis
    Minimal hepatic encephalopathy (MHE) represents the mildest form of hepatic encephalopathy (HE) seen in patients with liver dysfunction and/or portosystemic shunting [1]. MHE is characterized by subtle motor and cognitive deficits, affecting attention, speed of information processing, motor abilities and co-ordination [1,2]. The prevalence of MHE in adults with chronic liver disease (CLD) ranges from 30–84% [2,3]. This variation is attributed to differences in severity of liver disease, extent of portosystemic shunting, and cut-offs for abnormal neuropsychological tests (NPT) for diagnosing MHE [2].


    Date de mise en ligne : Vendredi 28 octobre 2016
    Jonel Trebicka
    Emergency TIPS in a Child-Pugh B patient: When does the window of opportunity open and close?
    Transjugular intrahepatic portosystemic shunt (TIPS) is used to treat complications of cirrhosis such as variceal bleeding and refractory ascites, but it also bears the risk of liver failure, overt hepatic encephalopathy (HE) and cardiac decompensation. Variceal bleeding may be controlled using endoscopic and medical treatment in patients with compensated cirrhosis; in decompensated patients, however, TIPS improves survival. Therefore, an early TIPS (within 72h or if later, still early after bleeding) might improve the survival of patients by preventing an inflammatory response and bacterial translocation.


    Date de mise en ligne : Vendredi 28 octobre 2016
    Florence Wong, Paolo Angeli
    New diagnostic criteria and management of acute kidney injury
    Traditionally, the diagnosis of renal dysfunction in cirrhosis is defined as a 50% increase in serum creatinine (SCr) with a final SCr of ⩾1.5mg/dl (133μmol/L) [1]. However, smaller rises in SCr have also been shown to have a negative prognostic impact in decompensated cirrhosis, especially in patients with infection [2]. Therefore, the International Club of Ascites, in line with other subspecialty communities, formally adapted the term acute kidney injury (AKI) to represent renal dysfunction in cirrhosis [3].


    Date de mise en ligne : Vendredi 28 octobre 2016
    Partha Mukhopadhyay, Béla Horváth, Mohanraj Rajesh, Zoltán V. Varga, Karim Gariani, Dongryeol Ryu, Zongxian Cao, Eileen Holovac, Ogyi Park, Zhou Zhou, Ming-Jiang Xu, Wei Wang, Grzegorz Godlewski, Janos Paloczi, Balazs Tamas Nemeth, Yuri Persidsky, Lucas Liaudet, György Haskó, Peter Bai, A. Hamid Boulares, Johan Auwerx, Bin Gao, Pal Pacher
    PARP inhibition protects against alcoholic and non-alcoholic steatohepatitis
    Chronic alcoholism is a leading cause of liver disease worldwide. The development of alcoholic steatohepatitis involves alcohol and acetaldehyde-induced direct hepatocyte injury and death by increasing reactive oxygen and nitrogen species (ROS/RNS) production, lipid peroxidation and oxidative DNA injury, coupled with overactivation of hepatic inflammatory processes (both innate and adaptive immunity) and reprograming of lipid metabolism by promoting hepatic lipid accumulation [1–4]. Non-alcoholic fatty liver disease (NAFLD) may also progress to steatohepatitis (non-alcoholic steatohepatitis; NASH).


    Date de mise en ligne : Jeudi 27 octobre 2016
    Manil D. Chouhan, Gareth Ambler, Rajeshwar P. Mookerjee, Stuart A. Taylor
    Multiparametric magnetic resonance imaging to predict clinical outcomes in patients with chronic liver disease: A cautionary note on a promising technique
    We have read the article by Pavlides et al. [1] with great interest. The potential of quantitative magnetic resonance (MR) methods to predict clinical outcomes in patients with chronic liver disease is an important area of research and T1 mapping is undoubtedly a promising technique [2,3]. The findings of Pavlides et al. are therefore of potential importance.


    Date de mise en ligne : Jeudi 27 octobre 2016
    Michael Pavlides, Rajarshi Banerjee, Catherine J. Kelly, Matthew D. Robson, Stefan Neubauer, Eleanor Barnes
    Reply to: “Multiparametric magnetic resonance imaging to predict clinical outcomes in patients with chronic liver disease: A cautionary note on a promising technique”
    We read with interest the letter by Chouhan et al., which raises several points for discussion in relation to our manuscript on “Multiparametric magnetic resonance imaging to predict clinical outcomes in patients with chronic liver disease” [1]. We agree that our study size is relatively small (in comparison to studies examining transient elastography or serum based biomarkers), and as such we are clear that we see this as a proof of principle study. Nevertheless, our study is the largest to date to report on the prognostic value of a magnetic resonance (MR) T1 mapping technique in the liver, and the relatively high adverse event rate of approximately 10% in this patient population (compared to the 4% in the transient elastography study in Calgary [2] and the 13% seen with ELF in a population that excluded extrahepatic disease [3]) allowed us to draw statistically significant conclusions regarding the ability of the MR to predict negative clinical outcomes in liver disease.


    Date de mise en ligne : Lundi 24 octobre 2016
    John J. Poterucha, Lawrence S. Friedman
    Evaluation of abnormal liver biochemical test results: Does the hare finally beat the tortoise?
    Gastroenterologists and hepatologists, especially those affiliated with an academic medical center, are often asked to consult on patients with abnormal liver biochemical test levels, and to share their approach with medical students, residents, sub-specialty fellows, and, even experienced providers. Usually, the approach centers around defining the abnormalities as acute or chronic, determining the degree and pattern of liver enzyme elevations (predominantly the serum alanine aminotransferase [ALT] or alkaline phosphatase level), and establishing whether or not liver function is impaired in terms of portal hypertension, jaundice, coagulopathy, or hypoalbuminemia.


    Date de mise en ligne : Lundi 24 octobre 2016
    Andreas Wannhoff, Kilian Friedrich, Daniel N. Gotthardt
    Reduced influence of procoagulant changes on survival in patients with advanced cirrhosis
    We read with interest the study by Kalambokis and colleagues reporting on the influence of a procoagulant imbalance, reflected by increased von Willebrand factor antigen (vWF-Ag) and increased Factor VIII-to-protein C-ratio (FVIII:PC-ratio), on survival in patients with liver cirrhosis [1].


    Date de mise en ligne : Samedi 22 octobre 2016
    Adriaan J. van der Meer, Jordan J. Feld, Harald Hofer, Piero L. Almasio, Vincenza Calvaruso, Conrado M. Fernández-Rodríguez, Soo Aleman, Nathalie Ganne-Carrié, Roberta D’Ambrosio, Stanislas Pol, Maria Trapero-Marugan, Raoel Maan, Ricardo Moreno-Otero, Vincent Mallet, Rolf Hultcrantz, Ola Weiland, Karoline Rutter, Vito Di Marco, Sonia Alonso, Savino Bruno, Massimo Colombo, Robert J. de Knegt, Bart J. Veldt, Bettina E. Hansen, Harry L.A. Janssen
    Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication
    Chronic infection with the hepatitis C virus (HCV) may lead to the development of hepatic fibrosis, which can ultimately progress to cirrhosis. Patients with cirrhosis have an increased risk to develop end-stage liver disease and hepatocellular carcinoma (HCC) [1]. A recent meta-analysis found that chronic HCV-infected patients with advanced hepatic fibrosis had an overall annual risk of 2.9% to experience liver failure, 3.2% to develop HCC and 2.7% to die of liver-related causes [2]. According to the current guidelines these patients should be included in HCC surveillance programs [3,4].


    Date de mise en ligne : Jeudi 20 octobre 2016
    Nathalie Goutté, Philippe Sogni, Noelle Bendersky, Jean Claude Barbare, Bruno Falissard, Olivier Farges
    Geographical variations in incidence, management and survival of hepatocellular carcinoma in a Western country
    Liver cancer, which is overrepresented by hepatocellular carcinoma (HCC), is the fifth most common cancer in men, the seventh most common cancer in women, and the second most common cause of cancer-related death worldwide [1,2]. Most cases of HCC occur in Sub-Saharan Africa and Eastern Asia, where incidence rates are high. South European countries have intermediate incidence rates, and the incidence in northern Europe, North America, and South America is low. Since the 1980s, the incidence of HCC has decreased in Asia, whereas it has increased in areas of low incidence such as North America and northern Europe [2].


    Date de mise en ligne : Mercredi 19 octobre 2016
    Magda Langiewicz, Andrea Schlegel, Enrica Saponara, Michael Linecker, Pieter Borger, Rolf Graf, Bostjan Humar, Pierre A. Clavien
    Hedgehog pathway mediates early acceleration of liver regeneration induced by a novel two-staged hepatectomy in mice
    The liver is unique with regards to its regenerative capacity. Its ability to regrow after tissue loss has permitted the surgical removal of large or multiple liver tumors with curative intent. Physiological limits to liver regeneration nevertheless exist. When the functional liver remnant is too small, the liver cannot recover vital function due to deficient hepatocyte proliferation [1,2]. In the clinic, resection-induced liver failure is known as the small-for-size syndrome (SFSS) and represents the most frequent cause of death due to liver surgery [3,4].


    Date de mise en ligne : Mercredi 19 octobre 2016
    Maud Lemoine, Mark R. Thursz
    Battlefield against hepatitis B infection and HCC in Africa
    Despite effective and safe hepatitis B virus (HBV) vaccine and antiviral therapies, HBV-related hepatocellular carcinoma (HCC) remains a major cause of deaths in young adults in Africa. There are multiple barriers to control the burden of HBV infection and HCC. In comparison to other major infectious diseases, HBV infection and liver diseases have received remarkably little attention from the global health community. There is an urgent need to improve birth dose vaccine coverage and implementing screening and treatment interventions.


    Date de mise en ligne : Vendredi 14 octobre 2016
    Mamatha Bhat, Peter Ghali, Benoît Dupont, Roy Hilzenrat, Mahmood Tazari, André Roy, Prosanto Chaudhury, Fernando Alvarez, Michel Carrier, Marc Bilodeau
    Proposal of a novel MELD exception point system for hepatocellular carcinoma based on tumor characteristics and dynamics
    The model for end-stage liver disease (MELD) system was implemented in transplant programs worldwide so as to enable allocation of liver transplant to those in most need, i.e., to those at higher risk of short-term death because of chronic liver failure (LF) [1], and to eliminate geographical disparity and time biases. The impetus for the development of this system was to shift the emphasis for allocation from favoring long waiting times to more severe illness, and in so doing to make the system more equitable [2].


    Date de mise en ligne : Jeudi 13 octobre 2016
    Yuchen Xia, Arnaud Carpentier, Xiaoming Cheng, Peter Daniel Block, Yao Zhao, Zhensheng Zhang, Ulrike Protzer, T. Jake Liang
    Human stem cell-derived hepatocytes as a model for hepatitis B virus infection, spreading and virus-host interactions
    Hepatitis B virus (HBV) remains a major public health threat with more than 240 million individuals chronically infected worldwide who are then at a high risk of developing liver cirrhosis and hepatocellular carcinoma (HCC) [1,2]. Currently, there are two classes of approved treatments: nucleos(t)ide analogs (NUC) and interferon-α (IFN-α). NUC targets viral polymerase, which limits virus replication, but cannot clear virus infection. Thus, patients need to take life-long treatment with the risk of developing drug resistance.


    Date de mise en ligne : Jeudi 13 octobre 2016
    Charles Béguelin, Darius Moradpour, Roland Sahli, Franziska Suter-Riniker, Alexander Lüthi, Matthias Cavassini, Huldrych F. Günthard, Manuel Battegay, Enos Bernasconi, Patrick Schmid, Alexandra Calmy, Dominique L. Braun, Hansjakob Furrer, Andri Rauch, Gilles Wandeler, Swiss HIV Cohort Study
    Hepatitis delta-associated mortality in HIV/HBV-coinfected patients
    Worldwide, 15–20 million people are infected with hepatitis delta virus (HDV), with the highest prevalence reported in regions endemic for hepatitis B virus (HBV) infection, such as Eastern and Mediterranean Europe, Sub-Saharan Africa (SSA) and parts of Asia [1,2]. It is estimated that 5–20% of HBV-infected individuals have serological evidence of exposure to HDV [3]. However, data on the prevalence of HDV in HIV/HBV-coinfected patients are scarce. Of a selected sample of 422 hepatitis B surface antigen (HBsAg) carriers in the EuroSIDA collaboration, 61 (14%) were coinfected with HDV [4].


    Date de mise en ligne : Jeudi 13 octobre 2016
    Sylvie Deuffic-Burban, Jérôme Boursier, Vincent Leroy, Yazdan Yazdanpanah, Laurent Castera, Philippe Mathurin
    Are targeted treatment recommendations in chronic hepatitis C tailored to diagnostic methods of fibrosis?
    The progression of chronic hepatitis C virus (HCV) infection varies significantly depending on patient characteristics. Around 20% of patients develop cirrhosis, while others never develop extensive fibrosis over 20years of infection [1,2]. We have previously shown that the patterns of the natural history of chronic hepatitis C (CHC) were significantly different in six European countries and that the impact of antiviral therapy in reducing the incidence of cirrhosis and deaths varies in these countries [3].


    Date de mise en ligne : Mardi 11 octobre 2016
    Mayuko Furuta, Masaki Ueno, Akihiro Fujimoto, Shinya Hayami, Satoru Yasukawa, Fumiyoshi Kojima, Koji Arihiro, Yoshiiku Kawakami, Christopher P. Wardell, Yuichi Shiraishi, Hiroko Tanaka, Kaoru Nakano, Kazuhiro Maejima, Aya Sasaki-Oku, Naoki Tokunaga, Keith A. Boroevich, Tetsuo Abe, Hiroshi Aikata, Hideki Ohdan, Kunihito Gotoh, Michiaki Kubo, Tatsuhiko Tsunoda, Satoru Miyano, Kazuaki Chayama, Hiroki Yamaue, Hidewaki Nakagawa
    Whole genome sequencing discriminates hepatocellular carcinoma with intrahepatic metastasis from multi-centric tumors
    Liver cancer is one of the most frequent and deadly cancers in the world, with an annual incidence of 0.25–1 million cases [1]. It is especially prevalent in Asia and Africa, and a rapid increase in its prevalence has been observed in Western countries, due to the increased incidence of viral infections and metabolic diseases. In most cases, hepatocellular carcinoma (HCC), a major type of liver cancer, develops in the background of chronic hepatitis or liver cirrhosis, caused by a hepatitis B viral (HBV) or hepatitis C viral (HCV) infection, alcoholism, or metabolic diseases [2].


    Date de mise en ligne : Samedi 08 octobre 2016
    Jiantao Ma, Shih-Jen Hwang, Alison Pedley, Joseph M. Massaro, Udo Hoffmann, Raymond T. Chung, Emelia J. Benjamin, Daniel Levy, Caroline S. Fox, Michelle T. Long
    Bi-directional analysis between fatty liver and cardiovascular disease risk factors
    Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in the US, affecting an estimated 20–30% of the adult population [1]. It is expected that the prevalence of NAFLD will continue to increase due to the rising incidence of obesity [2]. Hepatic steatosis or fatty liver is the defining characteristic of NAFLD [3,4], which can be assessed by either imaging or histology [1]. Several observational studies have demonstrated an association between NAFLD and risk for cardiovascular disease (CVD) [5–7].


    Date de mise en ligne : Mercredi 05 octobre 2016
    Elisabeth Schrumpf, Martin Kummen, Laura Valestrand, Thomas U. Greiner, Kristian Holm, Velmurugesan Arulampalam, Henrik M. Reims, John Baines, Fredrik Bäckhed, Tom H. Karlsen, Richard S. Blumberg, Johannes R. Hov, Espen Melum
    The gut microbiota contributes to a mouse model of spontaneous bile duct inflammation
    NOD.c3c4 mice spontaneously develop biliary inflammation in intrahepatic and extra-hepatic bile ducts [1]. The NOD.c3c4 model is developed on the NOD background [2]; a genetic background with increased susceptibility to autoimmune phenotypes similar to that seen in human biliary diseases [3]. The regular NOD mice also develop diabetes [4]. In contrast, NOD.c3c4 mice do not develop diabetes [2] and have been used as a model of the human biliary disease, primary biliary cirrhosis (PBC), as it develops autoantibodies and lymphocytic infiltrates similar to PBC [2].


    Date de mise en ligne : Mardi 04 octobre 2016
    Elliot B. Tapper, Sameer D. Saini, Neil Sengupta
    Extensive testing or focused testing of patients with elevated liver enzymes
    Elevated liver enzymes are common, affecting 7.9% of Americans [1]. While underlying liver disease in patients with elevated liver enzymes is often related to non-alcoholic fatty liver disease (NAFLD) (roughly 40% of patients) [2,3] or alcoholic liver disease (ALD) (roughly 25%), [1–6]; there are many etiologies for which management is fundamentally different and dependent on accurate diagnoses. These include common diseases like hepatitis B and C virus (HBV, HCV; roughly 8%) [1] and also rare diseases like primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) (both with a prevalence of roughly 0.01%) [7], autoimmune hepatitis (AIH) (0.001%) [8] and heritable metabolic liver diseases (hemochromatosis; 0.04–0.1%) [2,9], Wilson Disease (WD; 0.03%) [10] and alpha-1 antitrypsin deficiency (AATD; 0.04%) [11]).


    Date de mise en ligne : Samedi 01 octobre 2016
    Christoph Roderburg, Christian Trautwein
    Cell-specific functions of miRNA in the liver
    miRNAs play essential roles in virtually all cellular and biological processes including liver development, differentiation and homeostasis [1,2]. Altered expression levels of miRNAs were observed in patients with liver diseases e.g., liver steatosis, cirrhosis and hepatocellular carcinoma (HCC) [1,3]. Expression pattern of miRNAs are organ- and tissue-specific. In the liver, miRNAs are not homogeneously distributed but are selectively expressed and regulated in distinct hepatic cell types. For certain miRNAs, opposite regulation were described between the different liver cell compartments.


    Date de mise en ligne : Mercredi 28 septembre 2016
    Maneerat Chayanupatkul, Ronald Omino, Sahil Mittal, Jennifer R. Kramer, Peter Richardson, Aaron P. Thrift, Hashem B. El-Serag, Fasiha Kanwal
    Hepatocellular carcinoma in the absence of cirrhosis in patients with chronic hepatitis B virus infection
    Chronic hepatitis B (CHB) is a major risk factor for hepatocellular carcinoma (HCC), accounting for 50–55% of HCC cases worldwide [1,2]. Although cirrhosis is the precursor lesion for most HCCs, an estimated 0.1% of CHB patients without cirrhosis develop HCC annually [3], presumably through the direct carcinogenic effect of hepatitis B virus (HBV) [4]. However, this estimate is derived from studies of CHB patients in Asia and Europe [3], whereby most CHB patients develop perinatal or early childhood infections.


    Date de mise en ligne : Lundi 26 septembre 2016
    Javier Vaquero, Nathalie Guedj, Audrey Clapéron, Thanh Huong Nguyen Ho-Bouldoires, Valérie Paradis, Laura Fouassier
    Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks
    Cholangiocarcinoma (CCA) is an aggressive tumor with a poor prognosis due to its late clinical presentation and the lack of effective non-surgical therapies. Unfortunately, most of the patients are not eligible for curative surgery owing to the presence of metastases at the time of diagnosis. Therefore, it is important to understand the steps leading to cell dissemination in patients with CCA.To metastasize from the primary site, cancer cells must acquire migratory and invasive properties by a cell plasticity-promoting phenomenon known as epithelial-mesenchymal transition (EMT).


    Date de mise en ligne : Lundi 26 septembre 2016
    Won-Jung Shin, Jun-Gol Song, In-Gu Jun, Young-Jin Moon, Hye-Mee Kwon, Kyeowoon Jung, Seon-Ok Kim, Gyu-Sam Hwang
    Effect of ventriculo-arterial coupling on transplant outcomes in cirrhotics: Analysis of pressure-volume curve relations
    Cardiovascular abnormalities in advanced liver cirrhosis (LC) are characterized by a hyperdynamic circulation featuring increased heart rate and high cardiac output, concomitant with decreased systemic vascular resistance [1]. As LC progresses, cardiac dysfunction, known as cirrhotic cardiomyopathy, is associated with prognosis after transjugular intrahepatic portosystemic shunt [2,3] or liver transplantation (LT) [4–6]. Specifically, diastolic dysfunction has been more emphasized for estimating clinical outcome in cirrhotic patients, whereas systolic dysfunction has limited prognostic implications in hepatorenal syndrome patients [7].


    Date de mise en ligne : Samedi 24 septembre 2016
    Alessandro Vitale, Markus Peck-Radosavljevic, Edoardo G. Giannini, Eric Vibert, Wolfgang Sieghart, Sven Van Poucke, Timothy M. Pawlik
    Personalized treatment of patients with very early hepatocellular carcinoma
    Hepatocellular carcinoma (HCC), in its very early stage, is heterogeneous both in terms of liver function (i.e., presence or absence of portal hypertension, model for end-stage liver disease score, Child-Pugh score 5 or 6, bilirubin level) and tumor characteristics (i.e., location, alpha-fetoprotein values, pathological features such as microvascular invasion, tumor grade and satellitosis).Existing evidence in comparing different curative options for patients with very early HCC is poor due to small sample sizes and lack of solid subgroup analyses.


    Date de mise en ligne : Samedi 24 septembre 2016
    David J. Pinato, Rohini Sharma, Elias Allara, Clarence Yen, Tadaaki Arizumi, Keiichi Kubota, Dominik Bettinger, Jeong Won Jang, Carlo Smirne, Young Woon Kim, Masatoshi Kudo, Jessica Howell, Ramya Ramaswami, Michela E. Burlone, Vito Guerra, Robert Thimme, Mitsuru Ishizuka, Justin Stebbing, Mario Pirisi, Brian I. Carr
    The ALBI grade provides objective hepatic reserve estimation across each BCLC stage of hepatocellular carcinoma
    The mortality from hepatocellular carcinoma (HCC), the third most lethal malignancy on a global scale, is increasing despite best diagnostic and therapeutic efforts [1].


    Date de mise en ligne : Mardi 20 septembre 2016
    Mathieu Duché, Béatrice Ducot, Oanez Ackermann, Florent Guérin, Emmanuel Jacquemin, Olivier Bernard
    Portal hypertension in children: High-risk varices, primary prophylaxis and consequences of bleeding
    Primary prophylaxis of gastrointestinal (GI) bleeding due to portal hypertension is commonly performed in adult patients [1]. The pediatric gastroenterological community, however, has not wholly endorsed the concept of primary prophylaxis of bleeding for children with portal hypertension for several reasons [2–5]: 1) a lack of data allowing the definition of an endoscopic pattern of gastroesophageal varices predictive of a high-risk of bleeding that would justify preemptive treatment in all causes of childhood portal hypertension; 2) a lack of data concerning the efficacy and safety in children of primary prophylaxis of bleeding with beta-blocking drugs that are commonly used in adults; 3) the need, therefore, to resort to either endoscopic treatment of varices, portal surgery or transjugular intrahepatic portosystemic shunt (TIPS), and the limited number of studies reporting their use for primary prophylaxis of bleeding that would provide information concerning their efficacy and safety in children; 4) the opinion that, in children, the mortality of a first bleed is low and that its morbidity is unknown; and 5) in children with biliary atresia, the most common cause of childhood cirrhosis, there is a frequent need for liver transplantation early in life that treats portal hypertension as well as end-stage liver failure.


    Date de mise en ligne : Samedi 17 septembre 2016
    Kuan-hui Xiang, Eleftherios Michailidis, Hai Ding, Ya-qin Peng, Ming-ze Su, Yao Li, Xue-en Liu, Viet Loan Dao Thi, Xian-fang Wu, William M. Schneider, Charles M. Rice, Hui Zhuang, Tong Li
    Effects of amino acid substitutions in hepatitis B virus surface protein on virion secretion, antigenicity, HBsAg and viral DNA
    Chronic hepatitis B virus (HBV) infection remains a severe public health problem. About 240 million people worldwide are chronically infected and have an increased risk for developing liver cirrhosis and hepatocellular carcinoma [1,2]. The hepatitis B surface antigen (HBsAg), a major viral protein secreted into patient serum, consists of three distinct, but structurally related proteins: the large, middle and small hepatitis B surface proteins (LHBs, MHBs, and SHBs, respectively). Within the SHBs, the 99 to 169 amino acid (AA) region is termed as the major hydrophilic region (MHR), where AAs 124-147 is defined as the ‘a’ determinant, a dominant neutralizing epitope [3].


    Date de mise en ligne : Samedi 17 septembre 2016
    Patrick Ingiliz, Thomas C. Martin, Alison Rodger, Hans-Jürgen Stellbrink, Stefan Mauss, Christoph Boesecke, Mattias Mandorfer, Julie Bottero, Axel Baumgarten, Sanjay Bhagani, Karine Lacombe, Mark Nelson, Jürgen K. Rockstroh, NEAT study group
    HCV reinfection incidence and spontaneous clearance rates in HIV-positive men who have sex with men in Western Europe
    Liver disease represents a major cause of morbidity and mortality among patients infected with the human immunodeficiency virus (HIV) in the developed world [1]. In the setting of effective combined antiretroviral therapy (cART) and the successful preservation of a patient’s immune function, chronic infection with hepatitis C virus (HCV) is currently the main cause for liver related mortality due to liver failure and hepatocellular carcinoma [2,3].


    Date de mise en ligne : Samedi 17 septembre 2016
    Su Joa Ahn, Jeong Min Lee, Dong Ho Lee, Sang Min Lee, Jung-Hwan Yoon, Yoon Jun Kim, Jeong-Hoon Lee, Su Jong Yu, Joon Koo Han
    Real-time US-CT/MR fusion imaging for percutaneous radiofrequency ablation of hepatocellular carcinoma
    Percutaneous image guided radiofrequency ablation (RFA) is now widely performed in patients with early stage hepatocellular carcinomas (HCCs). It is a minimally invasive local treatment option in those who are considered unsuitable for surgical resection [1,2] as recommended by the American Association for the Study of Liver Disease (AASLD) and European Association for the Study of the Liver–European Organization for Research and Treatment of Cancer (EASL–EORTC) [3,4]. Indeed, several previous studies have demonstrated that RFA was able to achieve a significant extension of the life expectancy of patients with small HCCs (<3cm), with better cost effectiveness over surgery and other interventional procedures [5–8].


    Date de mise en ligne : Mercredi 14 septembre 2016
    Ching-Lung Lai, Danny Wong, Philip Ip, Malgorzata Kopaniszen, Wai-Kay Seto, James Fung, Fung-Yu Huang, Brian Lee, Giuseppe Cullaro, Chun Kong Chong, Ringo Wu, Charles Cheng, John Yuen, Vincent Ngai, Man-Fung Yuen
    Reduction of covalently closed circular DNA with long-term nucleos(t)ide analogue treatment in chronic hepatitis B
    Globally, chronic hepatitis B affects approximately 240 million people and contributes to more than 680,000 deaths annually [1]. Long-term nucleos(t)ide analogue treatment has been shown to be effective in suppression of the hepatitis B virus (HBV) replication to levels below the detection limits of polymerase chain reaction (PCR) assays, in histologic improvement (including reversal of cirrhosis), and in reducing the incidence of hepatocellular carcinoma [2–4]. Its long-term effect on intrahepatic covalently closed circular DNA (cccDNA) is less well documented.


    Date de mise en ligne : Samedi 27 août 2016
    Markus Cornberg, Vincent Wai-Sun Wong, Stephen Locarnini, Maurizia Brunetto, Harry L.A. Janssen, Henry Lik-Yuen Chan
    The role of quantitative hepatitis B surface antigen revisited
    In the past 10years, there has been a lot of enthusiasm surrounding the use of serum hepatitis B surface antigen (HBsAg) quantification to predict disease activity and monitor treatment response in chronic hepatitis B. The measurement of HBsAg levels have been standardized in IU/ml, and nowadays it is almost a mandatory measurement due to the development of new antiviral treatments aiming at HBsAg seroclearance, i.e., functional cure of hepatitis B. Recently, there has been an improved understanding of the molecular virology of HBsAg, and particularly the relative roles of covalently closed circular DNA and integrated hepatitis B virus (HBV) DNA.


    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.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Richard Moreau, Ramon Bataller, Thomas Berg, Jessica Zucman-Rossi, Rajiv Jalan
    From the Editor’s desk.....
    The most common cause of a patient being referred to secondary care is for the investigation of an abnormal liver function test, the cause of which is unknown and not obvious from initial consultation. Tapper et al. report the results of an important study evaluating the cost-effectiveness of using two approaches by simulating data of about 10,000 patients drawn from Britain and the US. They compared the cost-effectiveness of a ‘non-directed’ strategy whereby a whole battery of tests was ordered at the outset with, a ‘directed’ approach where tests were ordered in a step-wise manner.


    Date de mise en ligne : Jeudi 01 janvier 1970
    Contents


    Date de mise en ligne : Jeudi 01 janvier 1970
    EASL membership


    Date de mise en ligne : Jeudi 01 janvier 1970
    EASL Andrew K. Burroughs Short-term Training Fellowship


    Date de mise en ligne : Jeudi 01 janvier 1970
    EASL Monothematic Conference: Cholangiocytes in health and disease: From basic science to novel treatments. Oslo, Norway. 2017


    Date de mise en ligne : Jeudi 01 janvier 1970
    The International Liver Congress. Amsterdam, The Netherlands. 2017


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