Corrigendum to “Impaired brain glymphatic flow in experimental hepatic encephalopathy” [J Hepatol 69 (2019) 40–49]
The authors of this manuscript would like to thank Prof. David Attwell and his fellows for their offer of Isolectin and time on their confocal microscope. (Source: Journal of Hepatology)
Source: Journal of Hepatology - January 4, 2019 Category: Gastroenterology Authors: Anna Hadjihambi, Ian F. Harrison, Marta Costas-Rodr íguez, Frank Vanhaecke, Natalia Arias, Rocío Gallego-Durán, Svetlana Mastitskaya, Patrick S. Hosford, Steven W.M. Olde Damink, Nathan Davies, Abeba Habtesion, Mark F. Lythgoe, Alexander V. Gourine, Ra Tags: Corrigendum Source Type: research

Outcomes of radiofrequency ablation as first-line therapy for hepatocellular carcinoma less than 3  cm in potentially transplantable patients
The optimal approach for transplantable patients with early unifocal HCC is unclear. Small HCC (BCLC-0 or A) can be treated with ablation, liver resection, or liver transplantation (LT) as first-line therapies.1 Although the results of LT are excellent, most jurisdictions currently only assign model for end-stage liver disease (MELD) exception points to patients with larger HCC based on the belief that if resection or radiofrequency ablation (RFA) do not work, transplantation can be undertaken as a second curative procedure. (Source: Journal of Hepatology)
Source: Journal of Hepatology - January 4, 2019 Category: Gastroenterology Authors: Adam Doyle, Andre Gorgen, Hala Muaddi, Aloysious D. Aravinthan, Assaf Issachar, Oleg Mironov, Wei Zhang, John Kachura, Robert Beecroft, Sean P. Cleary, Anand Ghanekar, Paul D. Greig, Ian D. McGilvray, Markus Selzner, Mark S. Cattral, David R. Grant, Lesli Tags: Research Article Source Type: research

Fa(s)t assessment of the liver graft: Is it relevant?
Non-alcoholic fatty liver disease is one of the most frequent liver parenchymal conditions in Western countries and affects 25% of adults worldwide. It is mainly related to obesity that has become endemic, affecting 14 to 34% of individuals – including organ donors – in developed countries.1 Hepatic steatosis is the most frequent feature of non-alcoholic fatty liver disease and its presence represents the main cause of donor livers being declined, because of the risk of liver graft dysfunction.2 Hepatic steatosis appears in 2 main types: true microvesicular steatosis (mS), which is a rare condition, and macrove...
Source: Journal of Hepatology - January 3, 2019 Category: Gastroenterology Authors: Pierre Nahon, Olivier Soubrane Tags: Editorial Source Type: research

Gap junctions in liver disease: Implications for pathogenesis and therapy
Cell-to-cell communication is of extreme importance in tissue homeostasis, which is maintained by transmission of regulatory signals[1] (Figure 1). Intercellular communication via gap junctions (GJ) represents one of the most important routes of rapid signaling between cells. GJ channels span two plasma membranes and consist of two hemichannels (connexons), one belonging to each cell. Each hemichannel is formed by six connexin (Cx) subunits and is permeable to small molecules up to 1-1.5kD[1]. They serve to provide electrical and chemical conductance as well as metabolic assistance[2,3]. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 29, 2018 Category: Gastroenterology Authors: Manuel Hern ández-Guerra, Anna Hadjihambi, Rajiv Jalan Tags: Review Source Type: research

Treating Chronic Hepatitis Delta: The Need for Surrogate Markers of Treatment Efficacy
Chronic hepatitis delta represents the most severe from of chronic viral hepatitis. Its current treatment consist of the use of interferons and is largely unsatisfactory. Several new compounds are currently in development for hepatitis D virus (HDV) infection. However, surrogate markers for developing clinical endpoints in HDV infection are not well defined. The current manuscript aimed to evaluate existing data on treatment of HDV infection and to suggest treatment goals (possible “trial endpoints”) that could be used across different trials. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 26, 2018 Category: Gastroenterology Authors: Cihan Yurdaydin, Zaigham Abbas, Maria Buti, Markus Cornberg, Rafael Esteban, Ohad Etzion, Edward J. Gane, Robert G. Gish, Jeffrey S. Glenn, Saeed Hamid, Theo Heller, Christopher Koh, Pietro Lampertico, Yoav Lurie, Michael Manns, Raymundo Parana, Mario Riz Tags: Clinical Trial Watch Source Type: research

Prevalence and short-term mortality in a national US cohort with acute-on-chronic liver failure
Acute-on-chronic liver failure (ACLF) is a recently recognised condition characterised by multiorgan failure in patients with decompensated cirrhosis and associated with high short-term mortality.1 –3 (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 24, 2018 Category: Gastroenterology Authors: Ruben Hernaez, Jennifer R. Kramer, Yan Liu, Aylin Tansel, Yamini Natarajan, Khozema B. Hussain, Pere Gin ès, Elsa Solà, Richard Moreau, Alexander Gerbes, Hashem B. El-Serag, Fasiha Kanwal Source Type: research

It takes two “eyes” to see in depth
This study is particularly interesting since the whole spectrum of patients with cirrhosis was included, from patients with compensated disease to patients with refractory ascites.1 (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 24, 2018 Category: Gastroenterology Authors: Cristina Ripoll, Rafael Ba ñares, Alexander Zipprich Tags: Letter to the Editor Source Type: research

Quantitation of anti-HBe antibodies in anti-HBc-positive liver donors
There is increasing interest in quantitatively determining the presence of antibodies to hepatitis B virus (HBV) antigens both in patients with overt HBV infection and in those with occult HBV infection.1,2 Recently, we studied a cohort of 100 hepatitis B surface antigen (HBsAg)-negative/anti-HBc-positive liver donors and found that levels of anti-HBc of IgG class above a 4.4 cut-off index (COI) correlated with the finding of intrahepatic HBV covalently closed circular (ccc) DNA, providing a novel potential tool to identify individuals with occult HBV infection (OBI) at increased risk of HBV reactivation following pharmaco...
Source: Journal of Hepatology - December 24, 2018 Category: Gastroenterology Authors: Gian Paolo Caviglia, Francesco Tandoi, Antonella Olivero, Giorgio Maria Saracco, Mario Rizzetto, Renato Romagnoli, Antonina Smedile Tags: Letter to the Editor Source Type: research

Reply to: “Treatment for solitary hepatocellular carcinoma ranging from 2 and 5 cm: Is the curative effect of no-touch multibipolar radiofrequency ablation comparable to that of surgical resection?”
We thank Dr. Zhang and colleagues for their interest in our recently published article in the Journal of Hepatology.1 The authors raised several questions regarding our findings and conclusions. We would like to address the following points. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 24, 2018 Category: Gastroenterology Authors: Kayvan Mohkam, Jean-Yves Mabrut Tags: Letter to the Editor Source Type: research

Reply to: “It takes two “eyes” to see in depth”
We appreciate Ripoll and colleagues ’ comments regarding our study demonstrating that cardiac index (CI) is an independent predictor of disease outcomes in cirrhosis.1 As stated by Dr. Ripoll and colleagues, our study is the first attempt to give a precise definition of hyperdynamic circulation by using the upper limit of normal CI (>4.2  L/min/m2) as a cut-off. We also described a hypodynamic circulatory state (CI (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 24, 2018 Category: Gastroenterology Authors: Laura Turco, Guadalupe Garcia-Tsao, Rosario Rossi, Erica Villa, Filippo Schepis Tags: Letter to the Editor Source Type: research

Prevalence and Short-term Mortality of Acute-on-Chronic Liver Failure: a national cohort study from the USA
Acute-on-chronic liver failure (ACLF) is a recently recognized condition characterized by multi-organ failure in patients with decompensated cirrhosis and associated with high short-term mortality[1 –3] (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 24, 2018 Category: Gastroenterology Authors: Ruben Hernaez, Jennifer R. Kramer, Yan Liu, Aylin Tansel, Yamini Natarajan, Khozema B. Hussain, Pere Gines, Elsa Sola, Richard Moreau, Alexander Gerbes, Hashem B. El-Serag, Fasiha Kanwal Source Type: research

The long non-coding RNA LncHDAC2 drives the self-renewal of liver cancer stem cells via activation of Hedgehog signaling
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is one of the leading causes of cancer death globally. The highest incidence of HCC is in East and South-East Asia and Northern and Western Africa.1 However, the incidence of liver cancer, including HCC, has risen in areas with historically low rates, for instance, Western Europe, Northern America and parts of Oceania. Infection with hepatitis B virus and hepatitis C virus, as well as metabolic disorders, are etiologically responsible for HCC. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 21, 2018 Category: Gastroenterology Authors: Jiayi Wu, Pingping Zhu, Tiankun Lu, Ying Du, Yanying Wang, Luyun He, Buqing Ye, Benyu Liu, Liuliu Yang, Jing Wang, Yang Gu, Jie Lan, Yajing Hao, Lei He, Zusen Fan Tags: Research Article Source Type: research

Association between physical activity and risk of hepatobiliary cancers: A multinational cohort study
Liver cancer was the fourth leading cause of cancer death in 2015.1 Liver cancer is responsible for around 47,000 deaths per year in the European Union.2 Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer derived from hepatocytes and it accounts for 85 –90% of all primary liver cancers worldwide. It is the fifth most common cancer in men and the seventh most common cancer in women.1 The distribution of HCC varies greatly according to geographic location and it is more common in low- and middle-income countries than in developed countries. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 21, 2018 Category: Gastroenterology Authors: Sebastian E. Baumeister, Sabrina Schlesinger, Krasimira Aleksandrova, Carmen Jochem, Mazda Jenab, Marc J. Gunter, Kim Overvad, Anne Tj ønneland, Marie-Christine Boutron-Ruault, Franck Carbonnel, Agnès Fournier, Tilman Kühn, Rudolf Kaaks, Tobias Pischon Tags: Research Article Source Type: research

Normothermic regional perfusion vs. super-rapid recovery in controlled donation after circulatory death liver transplantation
Donation after circulatory death (DCD) donors, who are declared dead following cardiorespiratory arrest, are an increasingly common source of organs. The period of donor warm ischaemia surrounding arrest can damage the quality of organs in general and the liver in particular, because biliary cells are exquisitely susceptible to warm ischaemia.1 Thus, initial experiences with DCD liver transplantation described high rates of graft dysfunction and non-function and ischaemic type biliary lesions (ITBL). (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 21, 2018 Category: Gastroenterology Authors: Amelia J. Hessheimer, Elisabeth Coll, Ferr án Torres, Patricia Ruíz, Mikel Gastaca, José Ignacio Rivas, Manuel Gómez, Belinda Sánchez, Julio Santoyo, Pablo Ramírez, Pascual Parrilla, Luis Miguel Marín, Miguel Ángel Gómez-Bravo, Juan Carlos Garcí Tags: Research Article Source Type: research

Normothermic regional perfusion versus super rapid recovery in controlled donation after circulatory death liver transplantation
Donation after circulatory death (DCD) donors, which are declared dead following cardiorespiratory arrest, are an increasingly more common source of organs. The period of donor warm ischemia surrounding arrest can damage the quality of organs in general and the liver in particular, as biliary cells are exquisitely susceptible to warm ischemia (1). For this reason, initial experiences with DCD liver transplantation described high rates of graft dysfunction and non-function and ischemic type biliary lesions (ITBL). (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 21, 2018 Category: Gastroenterology Authors: Amelia J. Hessheimer, Elisabeth Coll, Ferr án Torres, Patricia Ruíz, Mikel Gastaca, José Ignacio Rivas, Manuel Gómez, Belinda Sánchez, Julio Santoyo, Pablo Ramírez, Pascual Parrilla, Luis Miguel Marín, Miguel Ángel Gómez-Bravo, Juan Carlos Garcí Source Type: research

Association of Physical Activity and Risk of Hepatobiliary Cancers: A Multinational Cohort Study
Liver cancer was the fourth leading cause of cancer death in 2015 [1]. Liver cancer is responsible for around 47,000 deaths per year in the European Union [2]. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer derived from hepatocytes and it accounts for 85-90% of all primary liver cancers worldwide. It is the fifth most common cancer in men and the seventh most common cancer in women [1]. The distribution of HCC varies greatly according to geographic location and it is more common in low- and middle-income countries than in developed countries. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 21, 2018 Category: Gastroenterology Authors: Sebastian E. Baumeister, Sabrina Schlesinger, Krasimira Aleksandrova, Carmen Jochem, Mazda Jenab, Marc J. Gunter, Kim Overvad, Anne Tj ønneland, Marie-Christine Boutron-Ruault, Franck Carbonnel, Agnès Fournier, Tilman Kühn, Rudolf Kaaks, Tobias Pischon Source Type: research

The long noncoding RNA LncHDAC2 drives the self-renewal of liver cancer stem cells via activation of Hedgehog Signaling
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is one of the leading lethal malignancies globally. The highest incidence of HCC is in East and South-East Asia and Northern and Western Africa[1]. However, the incidence of liver cancer, including HCC, has risen in areas with historically low rates, for instance, Western Europe, Northern America and parts of Oceania. Infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) as well as metabolic disorders is etiologically responsible for HCC[2]. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 21, 2018 Category: Gastroenterology Authors: Jiayi Wu, Pingping Zhu, Tiankun Lu, Ying Du, Yanying Wang, Luyun He, Buqing Ye, Benyu Liu, Liuliu Yang, Jing Wang, Yang Gu, Jie Lan, Yajing Hao, Lei He, Zusen Fan Source Type: research

Hepatocyte-specific suppression of microRNA-221-3p mitigates liver fibrosis
Liver fibrosis and cirrhosis contribute to more than 1 million deaths per year worldwide [1,2], 170,000 per year in Europe [3] and 33,539 per year in USA [4]. The underlying pathologies leading to fibrosis and subsequently cirrhosis include chronic virus infection, alcoholic steatohepatitis, and non-alcoholic steatohepatitis [5]. The manifestation of fibrosis is accompanied by the activation of quiescent hepatic stellate cells (HSCs), accumulation of excessive extra-cellular matrix and hepatocyte dysfunction leading to liver failure [6]. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 21, 2018 Category: Gastroenterology Authors: Hsin-Chieh Tsay, Qinggong Yuan, Asha Balakrishnan, Marina Kaiser, Selina M öbus, Emilia Kozdrowska, Marwa Farid, Pia-Katharina Tegtmeyer, Katharina Borst, Florian W.R. Vondran, Ulrich Kalinke, Andreas Kispert, Michael P. Manns, Michael Ott, Amar Deep Sha Source Type: research

Factors predicting early recurrence after surgical resection of hepatocellular carcinoma
We read with great interest the study by Dr. Chan et al.1 in which male gender, large tumor size, multinodular tumor, high albumin-bilirubin (ALBI) grade, high preoperative alpha-fetoprotein (AFP) level, and microvascular invasion were identified as independent risk factors of early recurrence ( (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 19, 2018 Category: Gastroenterology Authors: Yao-Ming Zhang, Zhen-Tao Zhou, Gao-Min Liu Tags: Letter to the Editor Source Type: research

The EASL International Liver Foundation: A growing pup with missions that are distinct yet integrated with those of its mother
Since 2014, the Governing Board of the European Association for the Study of Liver (EASL) has thoroughly explored the opportunities of setting up a foundation that could complement EASL ’s mission and increase its outreach in various arenas. In 2017, the EASL International Liver Foundation (EILF) was formally launched at the International Liver Congress, constituting a complementary entity to serve increasing demands and allowing for productive synergies between EASL and its foun dation arm in order to fundraise to reach complementary, yet common, objectives (Fig. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 18, 2018 Category: Gastroenterology Authors: Massimo Colombo, Tom Hemming Karlsen Tags: Editorial Source Type: research

Reply to: Correspondence concerning “Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection”
We are grateful for the interest in, and comment on,1 –4 our recent paper concerning early recurrence after resection of hepatocellular carcinoma (HCC).5 (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 18, 2018 Category: Gastroenterology Authors: Anthony W.H. Chan, Sarah Berhane, Alessandro Cucchetti, Philip J. Johnson Tags: Letter to the Editor Source Type: research

Age and Liver Transplantation
The average age of donors and recipients has increased over years in liver transplantation. Independent of the cause of liver disease, older candidates have more comorbidities, higher waitlist mortality and higher post-transplant mortality as compared to younger patients. However, transplant benefit may be similar in older and younger recipients, provided older recipients are carefully selected. The cohort of elder patients transplanted decades ago is also increasing raising issues concerning long-term exposure to immunosuppression and aging of the transplanted liver. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 18, 2018 Category: Gastroenterology Authors: Fran çois Durand, Josh Levitsky, François Cauchy, Hélène Gilgenkrantz, Olivier Soubrane, Claire Francoz Tags: Review Source Type: research

Metformin modulates innate immune-mediated inflammation and early progression of NAFLD-associated hepatocellular carcinoma in zebrafish
Hepatocellular Carcinoma (HCC) is a common cause of cancer-related deaths with increasing mortality worldwide [1]. In western societies, 30-40% of HCC patients are obese and have nonalcoholic steatohepatitis (NASH), an aggressive form of nonalcoholic fatty liver disease (NAFLD)[2 –5]. Abnormal lipid accumulation in hepatocytes increases oxidative stress and leads to lipotoxicity, which triggers liver inflammation, a hallmark in NAFLD progression to HCC[6]. Pro-tumorigenic subsets of neutrophils, macrophages, and other immune cells provide the tumor microenvironment (TME) w ith growth factors, matrix-remodeling factor...
Source: Journal of Hepatology - December 17, 2018 Category: Gastroenterology Authors: Sofia de Oliveira, Ruth A. Houseright, Alyssa L. Graves, Netta Golenberg, Benjamin G. Korte, Veronika Miskolci, Anna Huttenlocher Source Type: research

Acknowledgement to our reviewers
Good and timely peer review is absolutely essential for the success of the Journal of Hepatology. We are therefore extremely grateful for the support of so many colleagues who have dedicated their time this year. These reviewers have evaluated the research that was submitted to the journal, and shared their insights about the papers strengths and weaknesses. This has both enabled us to make the right editorial decisions, and helped our authors to further improve their work. Out of necessity, the role of the reviewer is anonymous and therefore, may go unnoticed at times. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 14, 2018 Category: Gastroenterology Source Type: research

EASL-AASLD HBV endpoints, London, United Kingdom, 2019
(Source: Journal of Hepatology)
Source: Journal of Hepatology - December 14, 2018 Category: Gastroenterology Source Type: research

Editorial Board
(Source: Journal of Hepatology)
Source: Journal of Hepatology - December 14, 2018 Category: Gastroenterology Source Type: research

EASL short-term training fellowship - Andrew K. Burroughs
(Source: Journal of Hepatology)
Source: Journal of Hepatology - December 14, 2018 Category: Gastroenterology Source Type: research

The International Liver CongressTM, Vienna, Austria, 2019
(Source: Journal of Hepatology)
Source: Journal of Hepatology - December 14, 2018 Category: Gastroenterology Source Type: research

EASL clinical school: Modern dilemmas in liver transplantation, University of Birmingham, United Kingdom, 2019
(Source: Journal of Hepatology)
Source: Journal of Hepatology - December 14, 2018 Category: Gastroenterology Source Type: research

EASL basic school: Metabolism, immunity and liver disease, Munich, Germany, 2019
(Source: Journal of Hepatology)
Source: Journal of Hepatology - December 14, 2018 Category: Gastroenterology Source Type: research

Contents
(Source: Journal of Hepatology)
Source: Journal of Hepatology - December 14, 2018 Category: Gastroenterology Source Type: research

JHEP at a glance (January 2019)
(Source: Journal of Hepatology)
Source: Journal of Hepatology - December 14, 2018 Category: Gastroenterology Source Type: research

EASL HCC Summit 2019, Lisbon, Portugal
(Source: Journal of Hepatology)
Source: Journal of Hepatology - December 14, 2018 Category: Gastroenterology Source Type: research

From the Editor ’s Desk
Identifying environmental factors associated with the development of non-alcoholic fatty liver disease (NAFLD) is a matter of intense research. Lactation has been shown to exert beneficial effects in both the child and the mother. Among its beneficial effects, lactation is known to lower triglycerides and to increase insulin sensitivity. In this issue of the Journal, Ajmera et al. studied if longer duration of lactation is associated with a lower prevalence of NAFLD in women. The study included a large cohort of young women who delivered one post-baseline birth or more and were followed for 25  years. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 14, 2018 Category: Gastroenterology Authors: Richard Moreau, Ramon Bataller, Thomas Berg, Sophie Lotersztajn, Jessica Zucman-Rossi, Rajiv Jalan Tags: Editorial Desk Source Type: research

Time to recurrence, but not recurrence-free survival, should be the endpoint of predicting early recurrence after HCC resection
In this study, gender, preoperative albumin-bilirubin (ALBI) grade, preoperative alpha-fetoprotein (AFP) level, tumor size, tumor number, and microvascular invasion were revealed as independent predictors associated with early recurrence after resection of hepatocellular carcinoma (HCC). Using these independent predictors, the authors developed and validated 2 models for predicting early recurrence, i.e., the preoperative model (ERASL-pre) and the postoperative model (ERASL-post). (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 13, 2018 Category: Gastroenterology Authors: Wen-Tao Yan, Bing Quan, Hao Xing, Meng-Chao Wu, Tian Yang Tags: Letter to the Editor Source Type: research

Predicting early hepatocellular carcinoma recurrence after resection: A comment for moving forward
Tumour recurrence, which occurs in 70% of patients with hepatocellular carcinoma (HCC) within 5  years after hepatic resection, is a major cause of post-resection death.1 This recurrence can be true recurrence (intrahepatic metastases), which occurs sooner than 2 years later, or it can be due to the development of de novo tumours at least 2 years later. Despite this high rate of tumour r ecurrence, no anti-recurrence adjuvant therapies are currently recommended by the European Association for the Study of the Liver (EASL)1 or the American Association for the Study of Liver Diseases (AASLD). (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 13, 2018 Category: Gastroenterology Authors: Xiao-Ying Zhang, Jie Ou, Jia-Yi Chen, Wen-Wu Li Tags: Letter to the Editor Source Type: research

Toward the universal scoring system in treatment for patients with hepatocellular carcinoma
With great interest, we read the article written by Chan et al. in a recent issue of “Journal of Hepatology”.1 The authors attempted to develop a new set of preoperative and postoperative scoring systems (ERASL) to predict the outcomes of hepatectomy for hepatocellular carcinoma (HCC), using a statistical approach and validating its prognostic utility in a large international co hort. Their preoperative score demonstrated decent statistical discrimination for 2-year recurrence-free survival (RFS) in their external validation cohort (C-index 0.601–0.672). (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 13, 2018 Category: Gastroenterology Authors: Jiro Kusakabe, Daniel J. Firl, Kazunari Sasaki Tags: Letter to the Editor Source Type: research

A serum protein factor mediates maturation and apoB-association of HCV particles in the extracellular milieu
Hepatitis C virus (HCV) infection is a major cause of chronic liver diseases worldwide. Although recent direct antiviral agents (DAA) can now cure most patients, it remains major challenges in basic, translational and clinical research[1]. As DAAs are only curative, the development of a protective vaccine remains an important goal; yet, this requires deeper knowledge of HCV particles structure. Indeed, HCV virion exhibits unusually heterogeneous particles in morphology, size and properties[2], as immunocapture of its surface proteins revealed particles of 50-80nm without symmetrical arrangement[3 –6]. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 13, 2018 Category: Gastroenterology Authors: Sol ène Denolly, Christelle Granier, Nelly Fontaine, Bruno Pozzetto, Thomas Bourlet, Maryse Guérin, François-Loïc Cosset Source Type: research

Platelet-Derived Growth Factor-D Enables Liver Myofibroblasts to Promote Tumor Lymphangiogenesis in Cholangiocarcinoma
Cholangiocarcinoma (CCA) originates from the intrahepatic or extrahepatic bile ducts and unfortunately, carries a very poor prognosis. [1] Despite of its increasing incidence, effective treatment options for CCA are scarce and limited to surgical resection or liver transplantation in few highly selected patients. [1] Less than one third of patients are eligible for curative surgery at the time of diagnosis due to a proclivity for early lymph node metastatization. [1,2] Although mechanisms promoting CCA invasiveness are still unclear, [3] the lymphatic vessels that develop within the tumor provide an important initial route...
Source: Journal of Hepatology - December 13, 2018 Category: Gastroenterology Authors: Massimiliano Cadamuro, Simone Brivio, Joachim Mertens, Marta Vismara, Anja Moncsek, Chiara Milani, Christian Fingas, Maria Cristina Malerba, Giorgia Nardo, Luigi Dall'Olmo, Eleonora Milani, Valeria Mariotti, Tommaso Stecca, Marco Massani, Carlo Spirli, Ro Source Type: research

Intraductal Papillary Neoplasm of the Bile Duct: Assessment of Invasive Carcinoma and Long-Term Outcomes using MRI
Intraductal papillary neoplasm of the bile duct (IPNB) is characterized by a papillary or villous biliary neoplasm covering delicate fibrovascular stalks and a histological spectrum ranging from benign disease to invasive malignancy.[1,2] According to the 2010 World Health Organization classification, IPNB can be classified into the following three histologic grades: IPNB with low- or intermediate-grade intraepithelial neoplasia, IPNB with high-grade intraepithelial neoplasia, and IPNB with an associated invasive carcinoma. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 13, 2018 Category: Gastroenterology Authors: Sunyoung Lee, Myeong-Jin Kim, Sohee Kim, Dongil Choi, Kee-Taek Jang, Young Nyun Park Source Type: research

Time to recurrence, but not recurrence-free survival, should be the endpoint used to predict early recurrence after HCC resection
In this study, gender, preoperative albumin-bilirubin (ALBI) grade, preoperative alpha-fetoprotein (AFP) level, tumor size, tumor number, and microvascular invasion were revealed as independent predictors associated with early recurrence after resection of hepatocellular carcinoma (HCC). Using these independent predictors, the authors developed and validated 2 models for predicting early recurrence, i.e., the preoperative model (ERASL-pre) and the postoperative model (ERASL-post). (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 12, 2018 Category: Gastroenterology Authors: Wen-Tao Yan, Bing Quan, Hao Xing, Meng-Chao Wu, Tian Yang Tags: Letter to the Editor Source Type: research

HCMV jogs the ‘memory’ of NK cells in HBV
The treatment paradigm in hepatitis B virus (HBV) is rapidly transforming with many new viral and immune therapies entering the clinical trial pipeline. Although many of the immune targets focus on restoration of the exhausted virus-specific T cell response1 an increasing body of work makes a case for natural killer (NK) cell-based immune therapies and vaccines.2 Advances in NK cell biology have revealed that these ‘innate’ cells may also possess adaptive features. These cells ‘sitting-on-the-fence’ of innate-adaptive immunity, undergo significant changes in their repertoire during differentiation. ...
Source: Journal of Hepatology - December 11, 2018 Category: Gastroenterology Authors: Upkar S. Gill, Lucy Golden-Mason Tags: Editorial Source Type: research

The trends in incidence of primary liver cancer caused by specific etiologies: results from the Global Burden of Disease Study 2016 and implications for liver cancer prevention
Liver cancer is a common lethal malignancy afflicting in excess of 1 million people and caused 800,000 deaths in 2016 worldwide.[1] It has been well documented that the incidence of liver cancer varies considerably across the world, with the highest incidence observed in East Asia. In contrast, the incidence in America is nearly five- to ten-folds lower than the incidence observed in East Asia.[2] Recent decreases in the incidence of liver cancer have been reported in China and Japan.[3 –5] However, newly diagnosed cases and the age standardized incidence rate of liver cancer have increased at global level during the...
Source: Journal of Hepatology - December 10, 2018 Category: Gastroenterology Authors: Zhenqiu Liu, Yanfeng Jiang, Huangbo Yuan, Qiwen Fang, Ning Cai, Chen Suo, Li Jin, Tiejun Zhang, Xingdong Chen Source Type: research

Serum hepatitis B core-related antigen (HBcrAg) correlates with covalently closed circular DNA transcriptional activity in chronic hepatitis B patients
The development of novel antiviral agents and immunomodulatory approaches to cure hepatitis B virus (HBV) infection requires new biomarkers capable of reflecting the intrahepatic activity of the virus and chronic HBV (CHB) stages and defining new meaningful treatment endpoints. Indeed, there is an unmet need for standardized assays able to provide mechanistic insights into the effects of the novel antiviral and immunomodulatory agents and to assess treatment efficacy.1 (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 7, 2018 Category: Gastroenterology Authors: Barbara Testoni, Fanny Leboss é, Caroline Scholtes, Françoise Berby, Clothilde Miaglia, Miroslava Subic, Alessandro Loglio, Floriana Facchetti, Pietro Lampertico, Massimo Levrero, Fabien Zoulim Tags: Research Article Source Type: research

Rosuvastatin improves the FGF19 analogue NGM282-associated lipid changes in patients with non-alcoholic steatohepatitis
Non-alcoholic steatohepatitis (NASH), a severe form of non-alcoholic fatty liver disease (NAFLD), represents a large and growing public health concern that is increasingly contributing to the rising prevalence of cirrhosis and hepatocellular carcinoma globally.1,2 Currently, there is no approved drug for NASH, which is projected to be the leading indication for liver transplantation in the next decade.3 The pathogenesis of NASH is complex, and it is hypothesized that toxic lipid species or intermediates may inflict hepatocyte injury. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 7, 2018 Category: Gastroenterology Authors: Mary E. Rinella, James F. Trotter, Manal F. Abdelmalek, Angelo H. Paredes, Margery A. Connelly, Mark J. Jaros, Lei Ling, Stephen J. Rossi, Alex M. DePaoli, Stephen A. Harrison Tags: Research Article Source Type: research

Rosuvastatin improves the FGF19 analogue NGM282-associated lipid changes in patients with nonalcoholic steatohepatitis
Non-alcoholic steatohepatitis (NASH), a severe form of non-alcoholic fatty liver disease (NAFLD), represents a large and growing public health concern that is increasingly contributing to the rising prevalence of cirrhosis and hepatocellular carcinoma globally[1,2]. Currently, there is no approved drug for NASH, which is projected to be the leading indication for liver transplantation in the next decade[3]. The pathogenesis of NASH is complex, and it is hypothesized that toxic lipid species or intermediates may inflict hepatocyte injury[4]. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 7, 2018 Category: Gastroenterology Authors: Mary E. Rinella, James F. Trotter, Manal F. Abdelmalek, Angelo H. Paredes, Margery A. Connelly, Mark J. Jaros, Lei Ling, Stephen J. Rossi, Alex M. DePaoli, Stephen A. Harrison Source Type: research

Serum Hepatitis B core-related antigen (HBcrAg) correlates with covalently-closed circular DNA transcriptional activity in chronic hepatitis B patients
The development of novel antiviral agents and immunomodulatory approaches to cure chronic HBV infection requires new biomarkers capable to reflect the intrahepatic activity of the virus and CHB stages and define new meaningful treatment endpoints. Indeed, there is an unmet need for standardized assays able to provide mechanistic insights into the effects of the novel antiviral and immuno-modulatory agents and to assess treatment efficacy[1]. (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 7, 2018 Category: Gastroenterology Authors: Testoni Barbara, Leboss é Fanny, Scholtes Caroline, Berby Françoise, Miaglia Clothilde, Subic Miroslava, Loglio Alessandro, Facchetti Floriana, Lampertico Pietro, Levrero Massimo, Zoulim Fabien Source Type: research

Evaluating the landscape of gene cooperativity with receptor tyrosine kinases in liver tumorigenesis using transposon-mediated mutagenesis
Hepatocellular carcinoma (HCC) is among the most aggressive cancers, with an increasing incidence, and few therapeutic options[1]. The exceptional investments on -omics studies over the last decade have unveiled not only an impressive list of alterations, but also a high degree of molecular heterogeneity between HCC patients[2,3]. The uniqueness of HCC in its alterations and heterogeneity may explain how treatments effective in other cancers have largely failed when applied to HCC[4]. Such context challenges the interpretation of -omics data, with the necessity to: 1) determine which of these alterations are functionally r...
Source: Journal of Hepatology - December 5, 2018 Category: Gastroenterology Authors: Yannan Fan, Sehrish K. Bazai, Fabrice Daian, Maria Arechederra, Sylvie Richelme, Nuri A. Temiz, Annie Yim, Bianca H. Habermann, Rosanna Dono, David A. Largaespada, Flavio Maina Source Type: research

Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: a phase III STAH trial
Primary liver cancer, including hepatocellular carcinoma (HCC), is the fifth and second commonest cancer and cause of cancer-related mortality, respectively, worldwide.[1] HCC prognosis remains poor owing to underlying chronic liver disease, late diagnosis, and frequent recurrence-progression after treatment; many patients with HCC are diagnosed at advanced stages.[2,3] (Source: Journal of Hepatology)
Source: Journal of Hepatology - December 5, 2018 Category: Gastroenterology Authors: Joong-Won Park, Yoon Jun Kim, Do Young Kim, Si-Hyun Bae, Seung Woon Paik, Youn-Jae Lee, Hwi Young Kim, Han Chu Lee, Sang Young Han, Jae Youn Cheong, Oh Sang Kwon, Jong Eun Yeon, Bo Hyun Kim, Jaeseok Hwang Source Type: research

8 weeks of sofosbuvir/ledipasvir is effective in DAA-naive non-cirrhotic HCV genotype 4 infected patients (HEPNED-001 study)
In contrast to genotype 1, genotype 4 hepatitis C (HCV) infections are more often found in Central Africa and the Middle East with the highest prevalence in Egypt.1 As the initial budget impact of HCV treatment with direct-acting antivirals (DAAs) can be substantial for countries with a high HCV prevalence,2 shortening treatment duration could help in reaching the World Health Organization ’s HCV elimination goals3 by lowering costs and expanding access.4 The most recent EASL guideline suggests 8 weeks of therapy with sofosbuvir/ledipasvir (SOF/LDV) as an option for treatment-naive non-cirrhotic patients with chron...
Source: Journal of Hepatology - December 4, 2018 Category: Gastroenterology Authors: Anne Boerekamps, Thomas Vanwolleghem, Marc van der Valk, Guido E. van den Berk, Marjo van Kasteren, Dirk Posthouwer, Anthonius S.M. Dofferhoff, Bart van Hoek, Dewkoemar Ramsoekh, Jelle Koopsen, Janke Schinkel, Eric Florence, Joop E. Arends, Bart J. Rijnde Tags: Letter to the Editor Source Type: research