Endoplasmic Reticulum stress signaling and the pathogenesis of Non-Alcoholic Fatty Liver Disease
The obesity epidemic is accompanied by a worldwide burden of non-alcoholic fatty liver disease (NAFLD) that manifests from simple steatosis to non-alcoholic steatohepatitis (NASH), possibly evolving into hepatocellular carcinoma (HCC). Although much attention has been focused on NAFLD, its pathogenesis remains largely obscure. The hallmark of NAFLD is the hepatic accumulation of lipids subsequently leading to cellular stress and hepatic injury, which eventually results in chronic liver disease. Abnormal lipid accumulation often coincides with insulin resistance in steatotic livers and is associated with perturbed endoplasm...
Source: Journal of Hepatology - June 22, 2018 Category: Gastroenterology Authors: Cynthia Lebeaupin, Deborah Vall ée, Younis Hazari, Claudio Hetz, Eric Chevet, Béatrice Bailly-Maitre Tags: Review Source Type: research

Impact of DAAs on liver transplantation: major effects on the evolution of indications and results. An ELITA study based on the ELTR registry
Viral hepatitis C has long been the most common indication for liver transplantation (LT) in Europe and in the US, with over 20% of all LT candidates on the waiting list having chronic hepatitis C virus infection (HCV). 1-2 Until recently, expected survival rates for HCV infected liver graft recipients was the lowest among all indications, due to severe and rapid HCV recurrence with IFN based therapies giving low cure rates.[1 –3] The approval of first generation direct-acting antiviral agents (DAAs), Telaprevir and Boceprevir, in 2011, marked the beginning of a new era. (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 22, 2018 Category: Gastroenterology Authors: Luca Saverio Belli, Giovanni Perricone, Rene Adam, Paolo A Cortesi, Mario Strazzabosco, Rita Facchetti, Vincent Karam, Mauro Salizzoni, Rafael Lopez Andujar, Costantino Fondevila, Paolo De Simone, Cristina Morelli, Joan Fabregat-Prous, Didier Samuel, Kosh Source Type: research

Beyond viral dependence: The pathological consequences of HCV-induced EGF signaling
Chronic hepatitis C virus (HCV) infection affects approximately 71  million individuals worldwide,1 being a major etiological factor for the development of liver cirrhosis and hepatocellular carcinoma (HCC). Acute HCV infection often progresses to chronicity and is characterized by a non-resolving liver inflammation leading to a broad range of alterations in the tissue microenvironment. About ninety percent of HCC cases arise in the context of chronic liver inflammation, highlighting the central role of this persistent immune response in disease pathogenesis. (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 21, 2018 Category: Gastroenterology Authors: Armando Andres Roca Suarez, Thomas F. Baumert, Joachim Lupberger Tags: Editorial Source Type: research

More than meets the eye: Severe alcoholic hepatitis can present as acute-on-chronic liver failure
Acute-on-chronic liver failure (ACLF) is a relatively new definition that recognises and classifies acute decompensation in chronic liver disease, cirrhosis, and links this to clinical prognostic predictions. While the concept of ACLF is generally accepted, experts from Europe (the European Association for the Study of the Liver) and Asian-Pacific regions (the Asian Pacific Association for the Study of the Liver) define ACLF by somewhat different criteria.1 –4 The general use of the ACLF terminology is also gaining interest amongst hepatologists in the United States. (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 20, 2018 Category: Gastroenterology Authors: Gyongyi Szabo Tags: Editorial Source Type: research

Allogeneic hematopoietic stem cell transplantation eliminates alloreactive inhibitory antibodies after liver transplantation for bile salt export pump deficiency
We report the first case of allogeneic hematopoietic stem cell transplantation (HSCT) for AIBD in a child refractory to intensive pharmacological immunosuppression and immunoadsorption. (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 20, 2018 Category: Gastroenterology Authors: Florian Brinkert, Ieva Pukite, Dorothee Krebs-Schmitt, Andrea Briem-Richter, Jan Stindt, Dieter H äussinger, Verena Keitel, Ingo Müller, Enke Grabhorn Tags: Case Report Source Type: research

Editorial Board
(Source: Journal of Hepatology)
Source: Journal of Hepatology - June 15, 2018 Category: Gastroenterology Source Type: research

EASL short-term training fellowship - Andrew K. Burroughs
(Source: Journal of Hepatology)
Source: Journal of Hepatology - June 15, 2018 Category: Gastroenterology Source Type: research

EASL NAFLD Summit 2018, Geneva, Switzerland
(Source: Journal of Hepatology)
Source: Journal of Hepatology - June 15, 2018 Category: Gastroenterology Source Type: research

EASL basic school: Liver vascular biology, Barcelona, Spain, 2018
(Source: Journal of Hepatology)
Source: Journal of Hepatology - June 15, 2018 Category: Gastroenterology Source Type: research

EASL clinical school: Diagnosis and management of vascular liver diseases, Bern, Switzerland, 2018
(Source: Journal of Hepatology)
Source: Journal of Hepatology - June 15, 2018 Category: Gastroenterology Source Type: research

Contents
(Source: Journal of Hepatology)
Source: Journal of Hepatology - June 15, 2018 Category: Gastroenterology Source Type: research

JHEP at a glance (July 2018)
(Source: Journal of Hepatology)
Source: Journal of Hepatology - June 15, 2018 Category: Gastroenterology Source Type: research

Discover the Hepahealth Project Report
(Source: Journal of Hepatology)
Source: Journal of Hepatology - June 15, 2018 Category: Gastroenterology Source Type: research

From the Editor ’s desk....
The changing frequency in the listing of patients with end-stage HCV-induced liver disease for transplant, and the improvement of the typically impaired post-transplant survival seen in these patients, can be taken as early and strong indicators of direct acting antiviral (DAA) therapy ’s positive impact on HCV-associated disease burden. The study by Crespo et al. compared the composition of the liver transplant waiting list and the early post-transplant survival in the years before and after the availability of DAAs. (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 15, 2018 Category: Gastroenterology Authors: Richard Moreau, Ramon Bataller, Thomas Berg, Jessica Zucman-Rossi, Rajiv Jalan Tags: Editorial Desk Source Type: research

The International Liver CongressTM, Vienna, Austria, 2019.
(Source: Journal of Hepatology)
Source: Journal of Hepatology - June 15, 2018 Category: Gastroenterology Source Type: research

Treatment of chronic hepatitis C
In areas where pangenotypic regimens are available, an 8-week course of glecaprevir/pibrentasvir or a 12-week regimen of velpatasvir/sofosbuvir can be used without the need for genotyping. However, genotyping is required for glecaprevir/pibrentasvir in pegylated interferon/ribavirin (PR)-experienced patients, as HCV genotype 3 infected patients cannot be treated for 8  weeks. In areas where these regimens are still not available/reimbursed, several other direct-acting antiviral (DAA)-combinations can be used (without the need for ribavirin), including 8-week regimen for certain subgroups. (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 8, 2018 Category: Gastroenterology Authors: Xavier Forns, Christoph Sarrazin Tags: Hepatology Snapshot Source Type: research

Is obesity a risk factor for the development of acute on chronic liver failure in patients with decompensated cirrhosis?
We read with great interest the article by Dr. Sundaram et al.[1] Using the United Network for Organ Sharing (UNOS) database, this large sample-size retrospective study identified that Class III obesity is an independent risk factor for the development of acute on chronic liver failure (ACLF) in patients with decompensated cirrhosis (HR = 1.24, 95% CI 1.09-1.41, P (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 8, 2018 Category: Gastroenterology Authors: Jiong-Jie Yu, Ju-Dong Li, Xin-Fei Xu, Feng Shen, Tian Yang Source Type: research

Modeling NAFLD Disease Burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease globally [1 –3]. This condition is characterized by excess liver fat in the absence of other causes such as alcohol consumption [4,5]. Obesity, type 2 diabetes mellitus (DM) and metabolic syndrome (MetS) are consistently identified as the most important risk factors for NAFLD [4,6]. (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 7, 2018 Category: Gastroenterology Authors: Chris Estes, Quentin M Anstee, Maria Teresa Arias-Loste, Heike Bantel, Stefeno Bellentani, Joan Caballeria, Massimo Colombo, Antonio Craxi, Javier Crespo, Christopher P. Day, Andreas Geier, Loreta A. Kondili, Jeffrey V. Lazarus, Rohit Loomba, Michael P. M Source Type: research

Multi organ assessment of Compensated Cirrhosis Patients using quantitative Magnetic Resonance Imaging
The evolution of liver cirrhosis to clinical liver related outcomes resulting from portal hypertension is not simply dictated by architectural and haemodynamic changes within the liver. Rather, advancing liver disease results in deleterious changes in a number of critical organs and the understanding of this process is a central aspect in the clinical management of cirrhotic patients. (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 7, 2018 Category: Gastroenterology Authors: Christopher R. Bradley, Eleanor F. Cox, Robert A. Scott, Martin W. James, Phillip Kaye, Guruprasad P. Aithal, Susan T. Francis, Indra Neil Guha Source Type: research

Regulation of Epithelial Injury and Bile Duct Obstruction by NLRP3 and IL-1R1 in Experimental Biliary Atresia
Biliary atresia (BA) results from a rapidly progressing inflammation and obstruction of extrahepatic bile ducts (EHBDs) in early infancy and is the most common indication for pediatric liver transplantation [1 –3]. The etiology of BA includes environmental triggers in the genetically susceptible host [4,5], followed by an over-activation of the neonatal immune response in the liver and EHBD [6,7]. We and others previously reported several cellular (dendritic cells [DCs], natural killer [NK] cells and CD 8+ T cells) and molecular (IL-8, IL-15, IFN-γ, TNFα) effectors of bile duct epithelial injury [8–...
Source: Journal of Hepatology - June 7, 2018 Category: Gastroenterology Authors: Li Yang, Tatsuki Mizuochi, Pranavkumar Shivakumar, Reena Mourya, Zhenhua Luo, Sridevi Gutta, Jorge A. Bezerra Source Type: research

Sofosbuvir/Velpatasvir for 12 Weeks in Genotype 1-4 HCV-Infected Liver Transplant Recipients
Among HCV-infected liver transplant recipients, HCV recurrence emerges in nearly all patients [1]. Within 5 years post-transplant, cirrhosis related to HCV ensues in approximately 30% of patients with recurrent, chronic HCV infection and is associated with increased graft loss rates and death [2 –5]. In the setting of post-transplant immunosuppression, the rate of hepatic fibrosis is accelerated in HCV-infected patients compared to the pre-transplant period [6]. (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 7, 2018 Category: Gastroenterology Authors: Kosh Agarwal, Llu ís Castells, Beat Müllhaupt, William M.C. Rosenberg, Brian McNabb, Sarah Arterburn, Gregory Camus, John McNally, Luisa M. Stamm, Diana M. Brainard, G. Mani Subramanian, Zoe Mariño, Jean-François Dufour, Xavier Forns Source Type: research

Efficacy of annexin A3 blockade in sensitizing hepatocellular carcinoma to sorafenib and regorafenib
Hepatocellular carcinoma (HCC) is a very aggressive disease and represents the third leading cause of cancer-related mortality worldwide [1]. Although treatment of HCC has greatly improved over the last decade, most HCC patients are presented with an underlying chronic liver disease and diagnosed only at advanced stages, when they are no longer eligible for curative therapies such as liver resection or transplantation [2]. In these cases, the multi-target tyrosine kinase inhibitor sorafenib is the only FDA-approved first-line systematic therapy, expanding patient median survival from 7.9 to 10.7 months [3 –5]. (Sourc...
Source: Journal of Hepatology - June 6, 2018 Category: Gastroenterology Authors: Man Tong, No élia Che, Lei Zhou, Steve T. Luk, Phillis W. Kau, Stella Chai, Elly S. Ngan, Chung-Mau Lo, Kwan Man, Jin Ding, Terence K. Lee, Stephanie Ma Source Type: research

Family occurrence of autoimmune hepatitis: A Danish nationwide registry-based cohort study
Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease with an incidence of 1 per 100.000 population per year around the world [1]. It is a frequently held notion that AIH accumulates in families [2], but the degree of familial clustering has rarely been studied. The existing literature suggests that AIH accumulates in twins [3,4], siblings [5], parents and children [3,6 –8], second-degree relatives [3], and family members of unspecified relationship [9,10], but those studies were limited by small numbers of patients and did not compare AIH incidence with the general population. (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 6, 2018 Category: Gastroenterology Authors: Lisbet Gr ønbæk, Hendrik Vilstrup, Lars Pedersen, Kaare Christensen, Peter Jepsen Source Type: research

Karnofsky Performance Status Before and After Liver Transplantation Predicts Graft and Patient Survival
The Karnofsky Performance Status (KPS) has been used for almost 70 years in clinical practice as a subjective ‘eyeball’ assessment of the overall performance status of patients. The KPS scores, administered by the provider or support staff, assign scores to patients on a scale of 0-100%, in increments of 10, where 100% is normal activity and 0% is dead [1]. It is widely used in general oncology practice as a prognostic predictor and also for the selection of patients in clinical trials [4–10]. The inter-observer reliability, validity and reproducibility of KPS scores in multiple clinical settings have sho...
Source: Journal of Hepatology - June 5, 2018 Category: Gastroenterology Authors: Paul J. Thuluvath, Avesh J. Thuluvath, Yulia Savva Source Type: research

hiPSC hepatocyte model demonstrates the role of unfolded protein response and inflammatory networks in α1-antitrypsin deficiency
α1-antitrypsin (A1AT) is a 52 kDa protein encoded by the SERPINA1 gene synthesized primarily by hepatocytes [1]. Secreted into the blood stream, it acts to control the function of neutrophil elastase, particularly in the lung [2]. A1AT also exerts anti-apoptotic and anti-inflammatory properties dur ing inflammation and hepatic injury. Most people carry the wildtype M allele, while the rarer Z variant (found in 1-3% of the population), is associated with the most common and severe form of clinically significant A1AT deficiency (A1ATD) [3]. (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 4, 2018 Category: Gastroenterology Authors: Charis-Patricia Segeritz, Sheikh Tamir Rashid, Miguel Cardoso de Brito, Maria Serra Paola, Adriana Ordonez, Carola Maria Morell, Joseph E. Kaserman, Pedro Madrigal, Nicholas Hannan, Laurent Gatto, Lu Tan, Andrew A. Wilson, Kathryn Lilley, Stefan J. Marcin Source Type: research

From the Editor ’s desk....
Alpha-1 antitrypsin deficiency (AATD) is a common genetic disorder causing chronic liver disease. The PiZ mutation results in misfolded alpha-1 antitrypsin protein (Z-AAT) leading to hepatocyte damage and progressive liver disease. It has been proposed that RNAi-based approaches that silence production of hepatic Z-AAT could be useful in these patients. In this issue, Turner et al. performed two important studies. First, they conducted a double-blind, randomised trial in healthy volunteers receiving escalating doses of the investigational agent ARC-AAT. (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 2, 2018 Category: Gastroenterology Authors: Richard Moreau, Ramon Bataller, Thomas Berg, Sophie Lotersztajn, Jessica Zucman-Rossi, Rajiv Jalan Tags: Editorial Desk Source Type: research

Reply to: “Protective effects of heme oxygenase 1 during ischemia-reperfusion injury: Hepatocytes or non parenchymal cells?”
We thank Xu et al. for their insightful comments on our recently published papers in Journal of Hepatology1 and American Journal of Transplantation,2 in which we documented the importance of macrophage heme oxygenase-1 (HO-1) on macrophage activation and graft autophagy regulation in the pathophysiology of hepatic ischemia-reperfusion injury (IRI). (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 2, 2018 Category: Gastroenterology Authors: Kojiro Nakamura, Min Zhang, Shoichi Kageyama, Bibo Ke, Jesus A. Araujo, Jerzy W. Kupiec-Weglinski Tags: Letter to the Editor Source Type: research

Protective effects of heme oxygenase 1 during ischemia reperfusion injury: Hepatocytes or non-parenchymal cells?
We thank Xu et al. for their insightful comments on our recently published papers in Journal of Hepatology [1] and American Journal of Transplantation [2], in which we documented the importance of macrophage heme oxygenase-1 (HO-1) on macrophage activation and graft autophagy regulation in the pathophysiology of hepatic ischemia-reperfusion injury (IRI). (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 2, 2018 Category: Gastroenterology Authors: Kojiro Nakamura, Min Zhang, Shoichi Kageyama, Bibo Ke, Jesus A. Araujo, Jerzy W. Kupiec-Weglinski Tags: Letter to the Editor Source Type: research

Reply to: “Influence of ablation technique on treatment failure for perivascular hepatocellular carcinoma”
We would like to thank Dr Mohkam and his colleagues ’ for their interest in our recent work.1 They have addressed the effectiveness of radiofrequency ablation (RFA) using multi-bipolar RF electrodes, especially the no-touch technique for the treatment of hepatocellular carcinoma (HCC), based on their recent study.2 (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 2, 2018 Category: Gastroenterology Authors: Sunyoung Lee, Tae Wook Kang Tags: Letter to the Editor Source Type: research

Reply to: “Relationship of hyperdynamic circulation and cardiodynamic states in cirrhosis”
We appreciate Dr. Alvarado and colleagues ’ comments regarding our study published in Journal of Hepatology describing that different cardiodynamic states (as determined by cardiac index at rest in a supine position) and systemic inflammation (as assessed by an elevated serum C reactive protein [CRP]) are independent predictors of disease outcomes in both compensated and decompensated patients with cirrhosis.1 (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 2, 2018 Category: Gastroenterology Authors: Laura Turco, Guadalupe Garcia-Tsao, Rosario Rossi, Erica Villa, Filippo Schepis Tags: Letter to the Editor Source Type: research

Reply to “The Relationship of Hyperdynamic Circulation and Cardiodynamic States in Cirrhosis”
We appreciate Dr. Alvarado and colleagues ’ comments regarding our study published in Journal of Hepatology describing that different cardiodynamic states (as determined by cardiac index at rest in a supine position) and systemic inflammation (as assessed by an elevated serum C reactive protein, CRP) are independent predictors of disease outcomes in both compensated and decompensated patients with cirrhosis. [1] (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 2, 2018 Category: Gastroenterology Authors: Laura Turco, Guadalupe Garcia-Tsao, Rosario Rossi, Erica Villa, Filippo Schepis Source Type: research

Feeding the Hedgehog: a new meaning for JNK signalling in liver regeneration
An unmatched characteristic of the liver is the ability to rebuild its lost mass either after toxic tissue damage or liver resection.[1] The latter is a well-established surgical technique, known as partial hepatectomy in which up to 70% of the entire liver can be removed.[1,2] Partial hepatectomy is used clinically as a treatment strategy for primary and selected metastatic liver cancers, and experimentally as a stimulus to study liver regeneration.[3] The main drawback of partial hepatectomy, however, is that not all patients with liver disease are candidates for liver resection. (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 2, 2018 Category: Gastroenterology Authors: Salvatore Papa, Concetta Bubici Source Type: research

Protective effects of heme oxygenase 1 during ischemia r epefrfsuion injury: Hepatocytes or non parenchymal cells?
We thank Xu et al. for their insightful comments on our recently published papers in Journal of Hepatology [1] and American Journal of Transplantation [2], in which we documented the importance of macrophage heme oxygenase-1 (HO-1) on macrophage activation and graft autophagy regulation in the pathophysiology of hepatic ischemia-reperfusion injury (IRI). (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 2, 2018 Category: Gastroenterology Authors: Kojiro Nakamura, Min Zhang, Shoichi Kageyama, Bibo Ke, Jesus A. Araujo, Jerzy W. Kupiec-Weglinski Tags: Letter to the Editor Source Type: research

From the Editor ’s Desk August 2018
Involvement of Yap1-TGF β-dependent epithelial mesenchymal transition (EMT) (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 2, 2018 Category: Gastroenterology Authors: Richard Moreau, Ramon Bataller, Thomas Berg, Sophie Lotersztajn, Jessica Zucman-Rossi, Rajiv Jalan Tags: Editorial Desk Source Type: research

Reply to “Influence of ablation technique on treatment failure for perivascular hepatocellular carcinoma”
We would like to thank Dr Mohkam and his colleagues ’ interest in our recent work.[1] They have addressed the effectiveness of radiofrequency ablation (RFA) using multi-bipolar RF electrodes, especially the no-touch technique for the treatment of hepatocellular carcinoma (HCC), based on their recent study.[2] (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 2, 2018 Category: Gastroenterology Authors: Sunyoung Lee, Tae Wook Kang Tags: Letter to the Editor Source Type: research

Author response: Is obesity a risk factor for the development of acute on chronic liver failure in patients with decompensated cirrhosis?
May 20, 2018 (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 31, 2018 Category: Gastroenterology Authors: Vinay Sundaram, David S. Goldberg, Rajiv Jalan Source Type: research

Towards a definite mouse model of NAFLD
The worldwide prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to be 24% and continues to increase significantly because of the rise in obesity and other metabolic disorders.1 Further, the number of patients quickly progressing to more severe stages of the disease is also increasing; in the US alone, non-alcoholic steatohepatitis (NASH) is already considered the second most common indication for liver transplantation, with prevalent NASH cases forecasted to increase to 27 million by 2030. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 29, 2018 Category: Gastroenterology Authors: Rui E. Castro, Anna Mae Diehl Tags: Editorial Source Type: research

Real-world data on antiviral treatments for hepatitis C virus infections: Can we define intention to treat or per protocol analyses?
We read with interest a recent study that used real-world (i.e. observational) data from the German Hepatitis C-Registry.1 The 12-week sustained virologic response (SVR) was compared between 8- and 12-week regimens of ledipasvir/sofosbuvir. The authors used classifications of intention to treat (ITT) and per protocol to define eligibility of patients for their analyses.1 One classification of ITT defined eligibility as patients who completed treatment with either the 8- or 12-week ledipasvir/sofosbuvir regimen (SVR ∼85%). (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 26, 2018 Category: Gastroenterology Authors: Rohit P. Ojha, Ewout W. Steyerberg Tags: Letter to the Editor Source Type: research

Influence of ablation technique on treatment failure for perivascular hepatocellular carcinoma
In this study, the authors reported that radiofrequency ablation (RFA) for perivascular (i.e. located le ss than 1 cm from large hepatic veins or portal branches) hepatocellular carcinoma (HCC) of less than 3 cm was associated with lower progression-free and overall survival than surgical resection (SR). (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 25, 2018 Category: Gastroenterology Authors: Kayvan Mohkam, Agn ès Rode, Jean-Yves Mabrut Tags: Letter to the Editor Source Type: research

Intestinal HIF-1 α Deletion Exacerbates Alcoholic Liver Disease through Inducing Intestinal Dysbiosis and Barrier Dysfunction
Alcoholic liver disease (ALD) ranges from hepatic steatosis to steatohepatitis, cirrhosis, and, potentially, hepatocellular carcinoma [1]. While alcohol induces deleterious effects in the liver, it also disrupts the gut microbiota homeostasis and intestinal epithelial integrity resulting in an increased permeability, bacterial translocation and release of bacteria-derived endotoxin into circulation [2 –4]. Clinical and experimental studies have demonstrated that serum levels of lipopolysaccharide (LPS) are indeed increased in alcoholic subjects [5,6]. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 24, 2018 Category: Gastroenterology Authors: Tuo Shao, Cuiqing Zhao, Fengyuan Li, Zelin Gu, Limimg Liu, Lihua Zhang, Yuhua Wang, Liqing He, Yunhuan Liu, Qi Liu, Yiping Chen, Hridgandh Donde, Rui Wang, Venkatakrishna R. Jala, Shirish Barve, Shao-Yu Chen, Xiang Zhang, Yongping Chen, Craig J. McClain, Source Type: research

Macrophages Contribute to the Pathogenesis of Sclerosing Cholangitis in Mice
Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease, characterized by chronic inflammation of the biliary epithelium and fibrous obliterative cholangitis of the intra- and extra-hepatic bile ducts. Its etiology and pathogenic mechanisms are still largely unknown, which contributes to the lack of effective therapies aside from liver transplantation. PSC patients are at high risk for the development of cirrhosis and its sequela of portal hypertension and end stage liver disease, and cholangiocarcinoma. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 23, 2018 Category: Gastroenterology Authors: Maria Eugenia Guicciardi, Christy E. Trussoni, Anuradha Krishnan, Steven F. Bronk, Maria J. Lorenzo Pisarello, Steven P. O'Hara, Patrick L. Splinter, Yandong Gao, Pamela Vig, Alexander Revzin, Nicholas F. LaRusso, Gregory J. Gores Source Type: research

Noninvasive Prediction of Esophageal Varices by Stiffness and Platelet in Nonalcoholic Fatty Liver Disease Cirrhosis
The pandemic spreading of obesity and diabetes makes nonalcoholic fatty liver disease (NAFLD) the growing most common cause of chronic liver disease and cirrhosis [1], an increasing risk factor for hepatocellular carcinoma [2], and the emerging indication for liver transplantation [3]. Consistent with these data the management of patients with NAFLD-related cirrhosis represents a challenge in terms of epidemiological, clinical and economical burden. In this complex picture, the diagnosis of esophageal varices (EV) and especially large (grade 2/3) EV requiring primary prophylaxis (varices needing treatment, VNT), is of para...
Source: Journal of Hepatology - May 23, 2018 Category: Gastroenterology Authors: Salvatore Petta, Giada Sebastiani, Elisabetta Bugianesi, Mauro Vigan ò, Vincent Wai-Sun Wong, Annalisa Berzigotti, Anna Ludovica Fracanzani, Quentin M. Anstee, Fabio Marra, Marco Barbara, Vincenza Calvaruso, Calogero Cammà, Vito Di Marco, Antonio Craxì Source Type: research

The P2X4 purinergic receptor regulates hepatic myofibroblast activation during liver fibrogenesis
Beside huge regenerative properties, the liver classically undergoes fibrogenesis in association with liver repair during chronic injury, impairing hepatic functions with high morbidity and mortality [1]. As well as in other organs, in the liver, the main cellular contributor to excessive extracellular matrix (ECM) deposition is the myofibroblast, derived from hepatic stellate cells and/or portal fibroblasts [2] after acute or during chronic liver injury. Hepatic myofibroblasts (hMF) are characterized by alpha smooth muscle actin ( α-SMA) expression, contractile properties, and by overexpressed ECM components and reg...
Source: Journal of Hepatology - May 23, 2018 Category: Gastroenterology Authors: Camille Le Guilcher, Isabelle Garcin, Olivier Dellis, Florent Cauchois, Ali Tebbi, Isabelle Doignon, Catherine Guettier, Boris Julien, Thierry Tordjmann Source Type: research

New virological tools for screening, diagnosis and monitoring of hepatitis B and C in resource-limited settings
Worldwide, the dominant model of laboratory testing is the centralized laboratory, in which automation of analytical processes increases, enabling the analysis of large numbers of samples at a relatively low cost. However, this trend does not fulfill the needs of chronic hepatitis B and C virus infection care in resource-limited settings. Alternative models using point-of-care (POC) tests and dried blood spots (DBS) are being increasingly considered for viral hepatitis screening, diagnosis and monitoring. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 22, 2018 Category: Gastroenterology Authors: St éphane Chevaliez, Jean-Michel Pawlotsky Tags: Review Source Type: research

Exploring new treatment paradigms for alcoholic hepatitis by extrapolating from NASH and cholestasis
Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease with 30-day mortality rate of up to 30%.[1] Corticosteroids are currently the only effective therapy but provide at best only short-term survival benefit.[2] Therefore, there is an urgent need to identify novel therapeutic targets for this lethal condition. Important pathways that have been the focus of treatment investigations include (1) bacterial and endotoxin translocation through disrupted gut barrier function (e.g. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 21, 2018 Category: Gastroenterology Authors: Thoetchai (Bee) Peeraphatdit, Douglas A. Simonetto, Vijay H. Shah Source Type: research

Pharmacogenomics of drug-induced liver injury (DILI): Molecular biology to clinical applications
A number of drug-specific and host-related factors contribute to the development of drug-induced liver injury (DILI). Investigations focused on genetic susceptibility to DILI have advanced our understanding of the pathogenesis of this rare, yet potentially life-threatening adverse reaction. Candidate gene studies involving well-characterized patients with DILI and drug-exposed controls have identified single nucleotide polymorphisms (SNPs) affecting the metabolism and clearance of specific drugs and hence, influencing individual ’s susceptibility to DILI. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 21, 2018 Category: Gastroenterology Authors: Kalaiyarasi Kaliyaperumal, Jane I. Grove, Robin M. Delahay, William J.H. Griffiths, Adam Duckworth, Guruprasad P. Aithal Tags: Grand Rounds Source Type: research

The relationship of hyperdynamic circulation and cardiodynamic states in cirrhosis
In a recent issue of the Journal Turco et al. report a cohort study assessing systemic and cardiac hemodynamics across stages of cirrhosis from compensated patients with mild portal hypertension (PH) to patients with refractory ascites.1 The authors defined three cardiodynamic states according to the cardiac index (CI): a hyperdynamic state defined by a CI above the upper normal limit (>4.2  L/min/m2), a (“relatively”) hypodynamic state with a CI below the average for the general population ( (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 18, 2018 Category: Gastroenterology Authors: Edilmar Alvarado, Marta Garcia-Guix, Sonia Mirabet, C àndid Villanueva Tags: Letter to the Editor Source Type: research

Response to: Positron emission tomography/computed tomography with 18F-fluorocholine improve tumor staging and treatment allocation in patients with hepatocellular carcinoma
We would like to comment on “Positron emission tomography/computed tomography with 18F-fluorocholine improve tumor staging and treatment allocation in patients with hepatocellular carcinoma” by colleagues Chalaye and Costentin et al.1 First, we would like to compliment the authors on this – despite the retrospective char acter – well designed and reported study. However, we would like to take the opportunity to highlight some issues, which require the authors’ further explanation. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 17, 2018 Category: Gastroenterology Authors: Walter Noordzij, Koert P. de Jong, Vincent E. de Meijer Tags: Letter to the Editor Source Type: research

Imaging endpoints for non-alcoholic steatohepatitis (NASH) therapeutic trials: A growing role for multiparametric MRI?
We read with great interest the excellent review article by Ratziu1 on endpoints for non-cirrhotic non-alcoholic steatohepatitis (NASH) therapeutic trials. Ratziu highlights that goals differ at different phases in the complex process of bringing novel medicines to patients (phase I, IIa, IIb and III) and that different endpoints to measure achievement of these goals are required for each phase of clinical development. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 17, 2018 Category: Gastroenterology Authors: Rajarshi Banerjee, Matthew Kelly, Henry Wilman, Teresa Wright, Stefan Neubauer Tags: Letter to the Editor Source Type: research

Protective effects of heme oxygenase 1 during ischemia-reperfusion injury: Hepatocytes or non-parenchymal cells?
Hepatic ischemia-reperfusion injury (IRI) remains an important issue in clinical procedures such as liver resection and organ transplantation and in the context of trauma and shock. Hepatic IRI may lead to poor early graft function and even acute or chronic organ rejection and may affect long-term patient/graft survival after liver transplantation. Although hepatic IRI is one of the major causes of morbidity and mortality in liver surgery, there are currently no effective therapeutic strategies to protect the liver from IRI. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 17, 2018 Category: Gastroenterology Authors: Dongwei Xu, Min Xu, Xiaoni Kong, Qiang Xia Tags: Letter to the Editor Source Type: research