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

Reply to: “Is obesity a risk factor for the development of acute-on-chronic liver failure in patients with decompensated cirrhosis?”
We thank Yu et al. for their interest in our manuscript, “Class III obesity is a risk factor for the development of acute-on-chronic liver failure in patients with decompensated cirrhosis.”1 Yu et al. raise several points regarding the statistical methodology and the variables incorporated in the study. We would like to address these comments. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 31, 2018 Category: Gastroenterology Authors: Vinay Sundaram, David S. Goldberg, Rajiv Jalan 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 by 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 gut microbiota homeostasis and intestinal epithelial integrity resulting in increased permeability, bacterial translocation and release of bacteria-derived endotoxin into the circulation.2 –4 Clinical and experimental studies have demonstrated that serum levels of lipopolysaccharide (LPS) are indeed increased in alcoholic individuals. (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, Tags: Research Article 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

Non-invasive prediction of esophageal varices by stiffness and platelet in non-alcoholic fatty liver disease cirrhosis
The pandemic spreading of obesity and diabetes makes non-alcoholic fatty liver disease (NAFLD) the most rapidly growing cause of chronic liver disease and cirrhosis,1 an increasing risk factor for hepatocellular carcinoma,2 and an 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 economic 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 paramount pr...
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 Tags: Research Article 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

Burden of liver disease in Europe: epidemiology and analysis of risk factors to identify prevention policies
The burden of liver disease in Europe continues to grow. We aimed to describe the epidemiology of liver diseases and their risk factors in European countries, and identify public health interventions that could impact on these risk factors to reduce the burden of liver disease. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 17, 2018 Category: Gastroenterology Authors: Laura Pimpin, Helena Cortez-Pinto, Francesco Negro, Emily Corbould, Jeffrey V. Lazarus, Laura Webber, Nick Sheron Tags: Seminar Source Type: research

Reply to: “Association of hepatitis E virus infection and myasthenia gravis: A pilot study”
Hepatitis E virus (HEV) has been associated with several extrahepatic, neurological manifestations.1,2 The associated neurological syndromes are most frequently subacute, post-infectious peripheral nervous system diseases including neuralgic amyotrophy and Guillain-Barre syndrome. In addition, infectious involvement of the central nervous system (HEV encephalitis) has been reported. When the genotype has been determined, neurological injury has almost exclusively been associated with HEV genotype 3 (HEV gt3), but case reports come from both developed and developing countries suggesting that HEV-associated neurological dama...
Source: Journal of Hepatology - May 15, 2018 Category: Gastroenterology Authors: Jeroen J.J. van Eijk, Pascal Cintas, Bart C. Jacobs, Nassim Kamar, Harry R. Dalton Tags: Letter to the Editor Source Type: research

From the Editor ’s desk...
High red and processed meat consumption, particularly increased intake of heterocyclic amines (HCAs) which are linked to oxidative stress, has been associated with type-2 diabetes. In this issue, Zelber et al. studied the association of meat consumption with non-alcoholic fatty liver disease (NAFLD) in a large cohort of patients. High consumption of total meat, red and/or processed meat were independently associated with higher odds of NAFLD and insulin resistance (IR), respectively, after adjusting for factors including BMI and physical activity. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 15, 2018 Category: Gastroenterology Authors: Richard Moreau, Ramon Bataller, Thomas Berg, Jessica Zucman-Rossi, Rajiv Jalan Tags: Editorial Desk Source Type: research

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

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

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

EASL clinical school: Abdominal sonography, Rotterdam, Netherlands, 2018
(Source: Journal of Hepatology)
Source: Journal of Hepatology - May 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 - May 15, 2018 Category: Gastroenterology Source Type: research

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

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

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

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

Erratum to “A new HDV mouse model identifies mitochondrial antiviral signaling protein (MAVS) as a key player in IFN-β induction” [J Hepatol 67 (2017) 669–679]
It has come to our attention that there were errors in Fig. 1A, Fig. 2A, and Fig. 8D and F in the published version of this manuscript. The corrected figures are provided below, with an explanation of the errors. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 15, 2018 Category: Gastroenterology Authors: Lester Su árez-Amarán, Carla Usai, Marianna Di Scala, Cristina Godoy, Yi Ni, Mirja Hommel, Laura Palomo, Víctor Segura, Cristina Olagüe, Africa Vales, Alicia Ruiz-Ripa, Maria Buti, Eduardo Salido, Jesús Prieto, Stephan Urban, Francisco Rodríguez-Fri Tags: Erratum Source Type: research

Herbal tea and liver injury – Tea extract or comedication can make a difference
With great interest we read the study by Alferink et al.1 and the following letter by Philips and Augustine.2 They raise the valid concern that green tea has been reported to cause severe liver injury (https://livertox.nih.gov/GreenTea.htm). (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 15, 2018 Category: Gastroenterology Authors: Andreas Benesic, Alexander L. Gerbes Tags: Letter to the Editor Source Type: research

Potential limitations of irradiation stent implantation in unresectable malignant biliary obstruction
Recently, Zhu et al. assessed the efficacy of the irradiation stent compared to the uncovered self-expandable metallic stent (SEMS) in patients with unresectable Bismuth-Corlette related malignant biliary obstruction (MBO).1 They showed that, compared with SEMS, the implantation of an irradiation stent provided prolonged stent patency, decreased rate of stent restenosis, and longer survival.1 Therefore, 125I seed-loaded stent is more promising than biliary stent alone for MBO because of the radiation effect of the particle. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 15, 2018 Category: Gastroenterology Authors: Hui-Chun Liu, Xiao-Si Hu, Qing Pang, Hao Jin, Yong Wang Tags: Letter to the Editor Source Type: research

Reply to: “Immune-related hepatitis with immunotherapy: Are corticosteroids always needed?”
We thank Gauci and colleagues for their interest in our paper “Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors”1. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 15, 2018 Category: Gastroenterology Authors: Eleonora De Martin, Jean-Marie Michot, Stephane Champiat, Olivier Lambotte, Caroline Robert, Aurelien Marabelle, Catherine Guettier, Didier Samuel Tags: Letter to the Editor Source Type: research

Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B
Hepatitis B virus (HBV) chronically infects around 250 million individuals worldwide and can cause liver cirrhosis as well as hepatocellular carcinoma (HCC).1 The treatment options for chronic hepatitis B (CHB) are either pegylated interferon-alfa (PEG-IFN α) or nucleos(t)ide analogues (NA). PEG-IFNα has the advantage of finite treatment with higher rates of anti-HBs seroconversion of around 10%, but is associated with considerable side effects.2 Thus, well-tolerated NAs are most commonly used. NAs efficiently suppress viral replication in most pati ents, have a beneficial effect on disease progression, and red...
Source: Journal of Hepatology - May 11, 2018 Category: Gastroenterology Authors: Franziska Rinker, Christine L. Zimmer, Christoph H öner zu Siederdissen, Michael P. Manns, Anke R.M. Kraft, Heiner Wedemeyer, Niklas K. Björkström, Markus Cornberg Tags: Research Article Source Type: research

Hepatic manifestations of telomere biology disorders
A 51-year-old Caucasian male was referred for evaluation of variceal bleeding. Laboratory tests were remarkable for mild thrombocytopenia and moderate alkaline phosphatase elevation. Synthetic liver function was well preserved. Abdominal computed tomography scan revealed moderate splenomegaly, gastric varices, and normal hepatic contour. A transjugular liver biopsy was performed revealing findings of nodular regenerative hyperplasia with no significant fibrosis or necroinflammatory activity. Hepatic venous pressure gradient was elevated at 31  mmHg, consistent with clinically significant portal hypertension. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 11, 2018 Category: Gastroenterology Authors: Mrinal M. Patnaik, Patrick S. Kamath, Douglas A. Simonetto Tags: Grand Rounds Source Type: research

Reply to: “Real-world data on antiviral treatments for hepatitis C virus infections: Can we define intention to treat or per protocol analyses?”
We thank Ojha and Steyerberg1 for making a valid point regarding our manuscript. Indeed, defining analysis populations of real-life observational studies as intention-to-treat or per protocol is problematic, as this wording may suggest a higher comparability to clinical trials than exists. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 11, 2018 Category: Gastroenterology Authors: Peter Buggisch, Stefan Zeuzem Tags: Letter to the Editor Source Type: research

Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg negative chronic hepatitis B
Hepatitis B virus (HBV) chronically infects around 250 million individuals worldwide and can cause liver cirrhosis as well as hepatocellular carcinoma (HCC) [1]. The treatment options for chronic hepatitis B (CHB) are either pegylated interferon-alfa (PEG-IFN α) or nucleos(t)ide analogues (NA). PEG-IFNα has the advantage of finite treatment with higher rates of anti-HBs seroconversion of around 10%, but is associated with considerable side effects [2]. Thus, well-tolerated NAs are most commonly used. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 11, 2018 Category: Gastroenterology Authors: Franziska Rinker, Christine L. Zimmer, Christoph H öner zu Siederdissen, Michael P. Manns, Anke R.M. Kraft, Heiner Wedemeyer, Niklas K. Björkström, Markus Cornberg Source Type: research

Real-world effectiveness of 8 weeks treatment with ledipasvir/sofosbuvir in chronic hepatitis C.
We thank Ojha and Steyerberg for making a good point. Indeed, defining analyses populations of real-life observational studies as ITT or PP is problematic as this wording may suggest a higher comparability to clinical trials as is adequate.In principle, even refined methods for adjusting confounders and minimizing bias cannot fully resolve the inherent problem of confounders in such trials. In our paper the wording (ITT and PP) was chosen for comparability with similar previous observational studies (e.g. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 11, 2018 Category: Gastroenterology Authors: Peter Buggisch, Stefan Zeuzem Tags: Letter to the Editor Source Type: research

Grand Rounds: Hepatic Manifestations of Telomere Biology Disorders
Clinical Case A 51 year old Caucasian male was referred for evaluation of variceal bleeding. Laboratory tests were remarkable for mild thrombocytopenia and moderate alkaline phosphatase elevation. Synthetic liver function was well preserved. Abdominal computed tomography scan revealed moderate splenomegaly, gastric varices, and normal hepatic contour. A transjugular liver biopsy was performed revealing findings of nodular regenerative hyperplasia (NRH) with no significant fibrosis or necroinflammatory activity. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 11, 2018 Category: Gastroenterology Authors: Mrinal M. Patnaik, Patrick S. Kamath, Douglas A. Simonetto Tags: Grand Rounds Source Type: research

Human liver infiltrating γδ T cells are composed of clonally expanded circulating and tissue-resident populations
γδ T cells are unconventional lymphocytes enriched in solid tissues, where they are thought to play critical roles in immunosurveillance [1]. Studies of mouse tissue-associated γδ subsets have suggest γδ T cell function can be predominantly innate-like, involving semi-invariant T cell subsets that enable fast response kinetics without a requirement for clonal selection and differentiation [2–5]. This role may allow for rapid ‘lymphoid stress surveillance’, limiting damage to host tissues in the face of microbial or non-microbial challenges, prior to full activation of a...
Source: Journal of Hepatology - May 11, 2018 Category: Gastroenterology Authors: Stuart Hunter, Carrie Willcox, Martin Davey, Sofya Kasatskaya, Hannah Jeffery, Dmitriy Chudakov, Ye Oo, Benjamin Willcox Source Type: research

Liver regeneration requires Yap1-TGF β-dependent epithelial-mesenchymal transition in hepatocytes
Adult liver has robust regenerative capacity as evidenced by efficient restitution of fully functional liver mass within days-weeks after acute 70% partial hepatectomy (PH) in mice and humans, respectively [1]. Paradoxically, chronically dysregulated repair of even minor liver damage causes defective recovery of healthy liver parenchyma and ultimately results in cirrhosis and/or liver cancer. Preventing these bad outcomes of liver injury is necessary to reduce mortality from liver disease, a major cause of premature death in adulthood worldwide [2]. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 11, 2018 Category: Gastroenterology Authors: Seh-Hoon Oh, Marzena Swiderska-Syn, Mark L. Jewell, Richard T. Premont, Anna Mae Diehl Source Type: research

Normal on-treatment ALT during antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B
Elevated alanine aminotransferase (ALT) above two times of the upper limit of normal (ULN) in patients with chronic hepatitis B (CHB) is one of the key indication for antiviral treatment recommended by international guidelines [1 –3]. Normal on-treatment ALT is often regarded as biochemical response to antiviral treatment. Being one of the most commonly used tests for CHB patients, ALT level correlates with hepatic necroinflammation [4]. The optimal ALT cutoffs are now set at 30 IU/L for men and 19 IU/L for women by the Am erican Association for the Study of Liver Diseases (AASLD) [3], as high-normal ALT levels accor...
Source: Journal of Hepatology - May 11, 2018 Category: Gastroenterology Authors: Grace Lai-Hung Wong, Henry Lik-Yuen Chan, Yee-Kit Tse, Terry Cheuk-Fung Yip, Kelvin Long-Yan Lam, Grace Chung-Yan Lui, Vincent Wai-Sun Wong Source Type: research

Genetic inactivation of Nrf2 prevents clonal expansion of initiated cells in a nutritional model of rat hepatocarcinogenesis
Hepatocellular carcinoma (HCC) is the second cause of cancer-related deaths worldwide[1]. Unfortunately, our knowledge of the genetic/epigenetic alterations implicated in HCC initiation and progression is still fragmentary and driving genetic alterations to which tumor cells are addicted and that can be targeted have not been identified. In this scenario, HCC is probably one of the tumor types where a more complete understanding of the underlying genetic alterations could have a major impact on the development of new treatment strategies. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 11, 2018 Category: Gastroenterology Authors: Claudia Orr ù, Marta Szydlowska, Keiko Taguchi, Patrizia Zavattari, Andrea Perra, Masayuki Yamamoto, Amedeo Columbano Source Type: research

Grand Rounds: Alcoholic Hepatitis
Alcoholic hepatitis presents with acute on chronic liver failure among patients with chronic and active heavy use of alcohol, with high short-term mortality. These patients suffer from two problems, namely hepatic dysfunction and alcohol use disorder. Short-term outcome is impacted by liver failure and the long-term outcome by alcoholism and relapse to alcohol use. Clearly, these patients need integrated and coordinated management from the beginning by multi-disciplinary team. Herein, we describe a clinical vignette on a 33 year old male patient who survived the first episode of alcoholic hepatitis with this integrated man...
Source: Journal of Hepatology - May 10, 2018 Category: Gastroenterology Authors: Ashwani K. Singal, Alexandre Louvet, Vijay H. Shah, Patrick S. Kamath Tags: Grand Rounds Source Type: research

Reply to: “Potential limitations of irradiation stent implantation in unresectable malignant biliary obstruction”
We would like to thank Liu et al. for their comments on our manuscript entitled “Irradiation stents vs. conventional metal stents for unresectable malignant biliary obstruction: a multicenter trial”.1 This manuscript reported a large-sample randomized trial to compare the irradiation stent with the uncovered self-expandable metallic stent for unresectable malignant biliary obstruction (MBO) at 20 centers in China. Liu et al. delivered criticisms concerning technical deficiency and a small portion of pathological diagnosis. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 8, 2018 Category: Gastroenterology Authors: Hai-Dong Zhu, Jian Lu, Gao-Jun Teng Tags: Letter to the Editor Source Type: research

Response to Letter to the Editor on “Irradiation stents vs. conventional metal stents for unresectable malignant biliary obstruction: a multicentre trial”
We would like to thank Liu et al for their comments on our manuscript entitled “Irradiation stents vs. conventional metal stents for unresectable malignant biliary obstruction: a multicentre trial” [1]. This manuscript reported a large-sample randomized trial to compare the irradiation stent with the uncovered self-expandable metallic stent (SEMS) for unresectable malignan t biliary obstruction (MBO) at 20 centers in China. Liu et al delivered criticisms concerning technical deficiency, small portion of pathological diagnosis, and a clerical error in the data from the Abstract section. (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 8, 2018 Category: Gastroenterology Authors: Hai-dong Zhu, Jian Lu, Gao-Jun Teng Source Type: research

Immune-related hepatitis with immunotherapy: Are corticosteroids always needed?
We read with interest the recent report of liver damage caused by monoclonal immune checkpoint inhibitors published by De Martin et al.1 (Source: Journal of Hepatology)
Source: Journal of Hepatology - May 7, 2018 Category: Gastroenterology Authors: Marie-L éa Gauci, Barouyr Baroudjian, Charlotte Zeboulon, Cécile Pages, Nicolas Poté, Olivier Roux, Mohamed Bouattour, Céleste Lebbé, PATIO group Tags: Letter to the Editor Source Type: research