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  • Hepatocellular carcinoma prediction beyond year 5 of oral therapy in a large cohort of Caucasian patients with chronic hepatitis B
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-22
    George V. Papatheodoridis; Vana Sypsa; George N. Dalekos; Cihan Yurdaydin; Florian Van Boemmel; Maria Buti; Jose Luis Calleja; Heng Chi; John Goulis; Spilios Manolakopoulos; Alessandro Loglio; Theodoros Voulgaris; Nikolaos Gatselis; Onur Keskin; Rhea Veelken; Marta Lopez-Gomez; Bettina E. Hansen; Savvoula Savvidou; Pietro Lampertico
    更新日期:2020-01-22
  • Precision medicine in variceal bleeding: Are we there yet?
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-22
    Marta Magaz; Anna Baiges; Virginia Hernández-Gea

    Variceal bleeding is one of the most feared complications of portal hypertension in patients with cirrhosis due to its deleterious impact on prognosis. Adequate management of patients at risk of developing variceal bleeding includes the prevention of the first variceal bleeding and rebleeding and therefore is crucial in modifying prognosis. The presence of clinically significant portal hypertension is the main factor determining the risk of development of varices and other liver related decompensations; therefore it should be carefully screened for and monitored. Treating patients with clinically significant portal hypertension based on their individual risk of portal hypertension related bleeding undoubtedly improves prognosis. The evaluation of liver hemodynamics and liver function can stratify patients according to their risk of bleeding and are no question useful tools in guiding therapy in an individualized manner. That said, recent data supports the idea that tailoring therapy in accordance with patient characteristics may effectively impact prognosis and increase survival in all clinical scenarios. This review will focus on evaluating the available evidence supporting individual risk characteristics for clinical decision-making and its impact in clinical outcome and survival. In primary prophylaxis, identification and treatment of patients with clinically significant portal hypertension improves decompensation-free survival. In the setting of acute variceal bleeding, the risk of failure and rebleeding can be easily predicted and thus stepping up treatment early during admission in adequate candidates (i. e. pre-emptive TIPS) can increase survival. Stratifying risk for the prevention of recurrent variceal bleeding taking into account liver function and hemodynamic response to non-selective beta-blockers allows tailoring treatment thereby increasing survival and avoiding adverse events.

    更新日期:2020-01-22
  • Hepatitis delta genotype 5 is associated with favourable disease outcome and better response to treatment compared to genotype 1
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-22
    Michelle Spaan; Ivana Carey; Matthew Bruce; Dazhuang Shang; Mary Horner; Geoff Dusheiko; Kosh Agarwal
    更新日期:2020-01-22
  • Advances in molecular classification and precision oncology in hepatocellular carcinoma
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Sandra Rebouissou; Jean-Charles Nault

    Hepatocellular carcinoma (HCC) arises from hepatocytes through the sequential accumulation of multiple genomic and epigenomic alterations resulting from Darwinian selection. Genes from various signalling pathways such as telomere maintenance, Wnt/β-catenin, P53/cell cycle regulation, oxidative stress, epigenetic modifiers, AKT/mTOR and MAP kinase are frequently mutated in HCC. Several subclasses of HCC have been identified based on transcriptomic dysregulation and genetic alterations that are closely related to risk factors, pathological features and prognosis. Undoubtedly, integration of data obtained from both preclinical models and human studies can help to accelerate the identification of robust predictive biomarkers of response to targeted biotherapy and immunotherapy. The aim of this review is to describe the main advances in HCC in terms of molecular biology and to discuss how this knowledge could be used in clinical practice in the future.

    更新日期:2020-01-15
  • Gut microbiome in HCC – Mechanisms, diagnosis and therapy
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Robert F. Schwabe; Tim F. Greten

    The microbiome exerts essential functions in health and disease, modulating key processes in metabolism, inflammation and immunity. Recent evidence has revealed a key role of the microbiome in carcinogenesis as well as anti-cancer immune responses in mouse models and patients. Herein, we will review functions of the gut microbiome in hepatocellular carcinoma (HCC), the third leading cause of worldwide cancer mortality. The majority of HCC develops in patients with chronic liver disease, caused by viral hepatitis, non-alcoholic fatty liver disease (NAFLD) and alcohol-related fatty liver disease. In this review, we will discuss mechanisms by which the gut-liver axis promotes the development of HCC in mouse models and patients, including dysbiosis, the leaky gut and bacterial metabolites, with a particular focus on NAFLD as the fastest growing cause of HCC development. Moreover, we will review recent progress in harnessing the gut microbiome as a potential diagnostic tool and novel therapeutic target in patients with HCC, in particular in the setting of immunotherapy.

    更新日期:2020-01-15
  • Novel patient-derived preclinical models of liver cancer
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Erin Bresnahan; Pierluigi Ramadori; Mathias Heikenwalder; Lars Zender; Amaia Lujambio

    Preclinical models of cancer based on the use of human cancer cell lines and mouse models have enabled discoveries that have been successfully translated into patients. And yet the majority of clinical trials fail, emphasising the urgent need to improve preclinical research to better interrogate the potential efficacy of each therapy and the patient population most likely to benefit. This is particularly important for liver malignancies, which lack highly efficient treatments and account for hundreds of thousands of deaths around the globe. Given the intricate network of genetic and environmental factors that contribute to liver cancer development and progression, the identification of new druggable targets will mainly depend on establishing preclinical models that mirror the complexity of features observed in patients. The development of new 3D cell culture systems, originating from cells/tissues isolated from patients, might create new opportunities for the generation of more specific and personalised therapies. However, these systems are unable to recapitulate the tumour microenvironment and interactions with the immune system, both proven to be critical influences on therapeutic outcomes. Patient-derived xenografts, in particular with humanised mouse models, more faithfully mimic the physiology of human liver cancer but are costly and time-consuming, which can be prohibitive for personalising therapies in the setting of an aggressive malignancy. In this review, we discuss the latest advances in the development of more accurate preclinical models to better understand liver cancer biology and identify paradigm-changing therapies, stressing the importance of a bi-directional communicative flow between clinicians and researchers to establish reliable model systems and determine how best to apply them to expanding our current knowledge.

    更新日期:2020-01-15
  • Epidemiology and surveillance for hepatocellular carcinoma: New trends
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Amit G. Singal; Pietro Lampertico; Pierre Nahon

    The burden of hepatocellular carcinoma (HCC) is highest in East Asia and Africa, although its incidence and mortality are rapidly rising in the United States and Europe. With the implementation of hepatitis B vaccination and hepatitis C treatment programmes worldwide, the epidemiology of HCC is shifting away from a disease predominated by viral hepatitis – an increasing proportion of cases are now attributable to non-alcoholic steatohepatitis. Surveillance using ultrasound, with or without alpha-fetoprotein, every 6 months has been associated with improved early detection and improved overall survival; however, limitations in implementation lead to a high proportion of HCC being detected at late stages in clinical practice. Herein, we review the current state of HCC surveillance and highlight areas for future research, including improved risk stratification of at-risk patients, surveillance tools with higher sensitivity and specificity for early HCC, and interventions to increase surveillance utilisation.

    更新日期:2020-01-15
  • Advances in resection and transplantation for hepatocellular carcinoma
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Eric Vibert; Myron Schwartz; Kim M. Olthoff

    It would be impossible to summarise all of the significant developments in the surgical management of hepatocellular carcinoma (HCC), even just over the past year, in a manuscript of this scope. Thus, we have selected topics for discussion that are the subject of current controversy and have attempted to present balanced points of view. Hepatic resection and transplantation are both mature modalities, and for the most part technical advances and improvements in candidate selection are incremental. The ability to readily cure hepatitis C stands out as the most impactful development in the field over recent years, especially in Western countries where hepatitis C has long been the chief aetiology underlying HCC and a predictor of poor outcomes after surgery, but its full implications remain to be clarified. The rising incidence of non-alcoholic steatohepatitis-related HCC and what it means with regard to surgical HCC management is an area of great current interest. With advancing technology, non-surgical locoregional treatments are gaining increasing application as potentially curative therapies. In addition, the advances in molecular and genomic assessment of HCC hold promise for personalising treatment and prognostication. The possible role of immunotherapy as an adjuvant to resection is being aggressively investigated. While liver surgery maintains an important role, the care of patients with HCC is more and more a team effort and needs to take place in the context of a well-integrated interdisciplinary programme to achieve the best outcomes for patients.

    更新日期:2020-01-15
  • Role of locoregional therapies in the wake of systemic therapy
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Daniel H. Palmer; Katerina Malagari; Laura M. Kulik

    Multiple systemic agents have recently been approved in the first- and second-line setting for hepatocellular carcinoma (HCC), increasing the therapeutic options for patients and treating physicians. The randomised controlled trials that led to these approvals were predominantly conducted in a population comprised of patients with advanced HCC. However, these trials also included a subset of patients who had progressed after locoregional therapies (LRTs), mostly transarterial chemoembolisation. With a greater number of systemic agents available, the role of LRTs has become a topic of debate, specifically regarding when to transition to systemic therapy in unresectable HCC and the potential opportunities for combining locoregional and systemic therapies. Trials of immuno-oncology agents (notably T cell checkpoint inhibitors) are ongoing in the advanced disease setting and these agents also present opportunities for combination therapies, both with other systemic agents and with LRTs in earlier stage disease. This article will review strategies to guide patient selection for LRT as well as the development of locoregional-systemic combinations based on scientific rationale and the challenges of clinical trial design in this setting.

    更新日期:2020-01-15
  • mRECIST for HCC: Performance and novel refinements
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Josep M. Llovet; Riccardo Lencioni

    In 2010, modified RECIST (mRECIST) criteria were proposed as a way of adapting the RECIST criteria to the particularities of hepatocellular carcinoma (HCC). We intended to overcome some limitations of RECIST in measuring tumour shrinkage with local and systemic therapies, and also to refine the assessment of progression that could be misinterpreted with conventional RECIST 1.1, due to clinical events related to the natural progression of chronic liver disease (development of ascites, enlargement of lymph nodes, etc.). mRECIST has served its purpose since being adopted or included in clinical practice guidelines (European, American and Asian) for the management of HCC; it has also been instrumental for assessing response and time-to-event endpoints in several phase II and III investigations. Nowadays, mRECIST has become the standard tool for measurement of radiological endpoints at early/intermediate stages of HCC. At advanced stages, guidelines recommend both methods. mRECIST has been proven to capture higher objective response rates in tumours treated with molecular therapies and those responses have shown to be independently associated with better survival. With the advent of novel treatment approaches (i.e. immunotherapy) and combination therapies there is a need to further refine and clarify some concepts around the performance of mRECIST. Similarly, changes in the landscape of standard of care at advanced stages of the disease are pointing towards progression-free survival as a potential primary endpoint in some phase III investigations, as effective therapies applied beyond progression might mask overall survival results. Strict recommendations for adopting this endpoint have been reported. Overall, we review the performance of mRECIST during the last decade, incorporating novel clarifications and refinements in light of emerging challenges in the study and management of HCC.

    更新日期:2020-01-15
  • Challenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Ann-Lii Cheng; Chiun Hsu; Stephen L. Chan; Su-Pin Choo; Masatoshi Kudo

    Immune checkpoint inhibitor (ICI) therapy targeting anti-programmed cell death-1 (anti-PD-1) or its ligand (anti-PD-L1) is the backbone of numerous combination regimens aimed at improving the objective response and survival of patients with hepatocellular carcinoma (HCC). Clinical trials of immuno-oncology regimens in other cancer types have shed light on issues of study design, including how to choose candidate regimens based on early-phase trial results, statistical considerations in trials with multiple primary endpoints, and the importance of predictive biomarkers. In this review, the updated data from early-phase trials of combination immunotherapy for HCC are summarised. Since the most extensively tested combination regimens for advanced HCC comprise anti-PD-1/anti-PD-L1 agents plus antiangiogenic agents, the relative benefit and antitumor mechanism of antiangiogenic multikinase inhibitors versus specific VEGF/VEGFR inhibitors are discussed. Other critical issues in the development of combination immunotherapy, including optimal management of immune-related adverse events and the value of ICI therapy in combination with locoregional treatment for HCC, are also explored.

    更新日期:2020-01-15
  • Diagnosis and management of toxicities of immune checkpoint inhibitors in hepatocellular carcinoma
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Bruno Sangro; Stephen L. Chan; Tim Meyer; María Reig; Anthony El-Khoueiry; Peter R. Galle

    Immune checkpoint inhibitors (ICIs) have reshaped cancer therapy. ICIs enhance T cell activation through various mechanisms and may help reverse the exhausted phenotype of tumour-infiltrating lymphocytes. However, disrupting the key role that checkpoint molecules play in immune homeostasis may result in autoimmune complications. A broad range of immune-related adverse events (irAEs) involve almost every organ but mostly affect the skin, digestive system, lung, endocrine glands, nervous system, kidney, blood cells, and musculoskeletal system. They are usually manageable but can be life-threatening. The incidence of irAEs is not very different in patients with hepatocellular carcinoma (HCC) compared to other tumour types, although there is a trend towards a higher incidence of hepatic irAEs. HCC usually develops on a background of cirrhosis with associated systemic manifestations. Extrahepatic organ dysfunction in cirrhosis may cause signs and symptoms that overlap with irAEs or increase their severity. Available guidelines for the management of irAEs have not specifically considered the assessment of toxicities in the context of patients with liver cancer and cirrhosis. This review addresses the toxicity profile of ICIs in patients with HCC, focusing on the challenges that the underlying liver disease poses to their diagnosis and management. Challenges include late recognition, inadequate work-up and delayed treatment, overdiagnosis and inappropriate interruption of ICIs, complications caused by immunosuppressive therapy, and increased cost. A specific algorithm for the management of hepatic irAEs is provided.

    更新日期:2020-01-15
  • Molecular therapies for HCC: Looking outside the box
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Sandrine Faivre; Lorenza Rimassa; Richard S. Finn

    Over the past decade, sorafenib has been the only systemic agent with proven clinical efficacy for patients with unresectable hepatocellular carcinoma (HCC). Recently, lenvatinib was shown to be non-inferior to sorafenib, while regorafenib, cabozantinib, and ramucirumab were shown to be superior to placebo in patients failing sorafenib. In addition, trials of immune checkpoint inhibitors reported encouraging efficacy signals. However, apart from alpha-fetoprotein, which is used to select patients for ramucirumab, no biomarkers are available to identify patients that may respond to a specific treatment. Different synergisms have been postulated based on the potential interplay between antiangiogenic drugs and immunotherapy, with several clinical trials currently testing this hypothesis. Indeed, encouraging preliminary results of phase I studies of bevacizumab plus atezolizumab and lenvatinib plus pembrolizumab have led to the design of ongoing phase III trials, including both antiangiogenics and immune checkpoint inhibitors in the front-line setting. Other important phase II studies have tested molecular therapies directed against different novel targets, such as transforming growth factor-beta, MET (hepatocyte growth factor receptor), and fibroblast growth factor receptor 4. These studies integrated translational research with the aim of better defining the biological tumour profile and identifying tumour and blood biomarkers that select patients who may really benefit from a specific molecular therapy. Importantly, good safety profiles make these drugs suitable for future combinations. In this review, we discuss the most recent data on novel combination strategies and targets, as well as looking ahead to the future role of molecular therapies in the treatment of patients with advanced HCC.

    更新日期:2020-01-15
  • Systemic therapies for intrahepatic cholangiocarcinoma
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Robin Kate Kelley; John Bridgewater; Gregory J. Gores; Andrew X. Zhu

    Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal hepatobiliary neoplasm whose incidence is increasing. Largely neglected for decades as a rare malignancy and frequently misdiagnosed as carcinoma of unknown primary, considerable clinical and investigative attention has recently been focused on iCCA worldwide. The established standard of care includes first-line (gemcitabine and cisplatin), second-line (FOLFOX) and adjuvant (capecitabine) systemic chemotherapy. Compared to hepatocellular carcinoma, iCCA is genetically distinct with several targetable genetic aberrations identified to date. Indeed, FGFR2 and NTRK fusions, and IDH1 and BRAF targetable mutations have been comprehensively characterised and clinical data is emerging on targeting these oncogenic drivers pharmacologically. Also, the role of immunotherapy has been examined and is an area of intense investigation. Herein, in a timely and topical manner, we will review these advances and highlight future directions of research.

    更新日期:2020-01-15
  • Liver resection and transplantation for intrahepatic cholangiocarcinoma
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Vincenzo Mazzaferro; Andre Gorgen; Sasan Roayaie; Michele Droz dit Busset; Gonzalo Sapisochin

    The incidence of intrahepatic cholangiocarcinoma (iCCA) is increasing worldwide. Although several advances have been made in the past decades to better understand this complex malignancy and to develop new treatment strategies, the prognosis of iCCA remains dismal. Liver resection (LR) is the mainstay of treatment but only a minority of patients are amenable to surgery. In most cases, patients with iCCA will require a major hepatectomy for complete resection of the tumour. This may be contraindicated or increase the surgical burden in patients with chronic liver disease and small remnant liver volume. Lymphadenectomy with a minimal harvest of 6 lymph nodes is considered adequate, as microscopic nodal metastases have been shown in more than 40% of patients. Current 5-year overall survival following LR is in the range of 25%–40%. For locally advanced disease not amenable to upfront LR, neoadjuvant locoregional therapies may be used with the aim of converting these patients to resectability or even to transplantation in well-selected cases. Recent studies have shown that liver transplantation (LT) might be a treatment option for patients with unresectable very-early iCCA (i.e. ≤2 cm), with survival outcomes comparable to those of hepatocellular carcinoma. In patients with unresectable, advanced tumours, confined to the liver who achieve sustained response to neoadjuvant treatment, LT may be considered an option within prospective protocols. The role of adjuvant therapies in iCCA is still under debate. Herein, we review the recent advances in the surgical treatment of iCCA and examine its correlation with locoregional therapies, adjuvant and neo-adjuvant strategies.

    更新日期:2020-01-15
  • Long-term outcome of decompensated alcohol-related liver disease with steatohepatitis and Maddrey’s discriminant function <32.
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Delphine Degré; Rudolf E. Stauber; Gaël Englebert; Francesca Sarocchi; Laurine Verset; Florian Rainer; Walter Spindelboeck; Hassane Njimi; Eric Trépo; Thierry Gustot; Carolin Lackner; Pierre Deltenre; Christophe Moreno
    更新日期:2020-01-15
  • Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Michael Praktiknjo; Macarena Simón-Talero; Julia Römer; Davide Roccarina; Javier Martínez; Katharina Lampichler; Anna Baiges; Gavin Low; Elba Llop; Martin H. Maurer; Alexander Zipprich; Michela Triolo; Geert Maleux; Annette Dam Fialla; Claus Dam; Judit Vidal-González; Avik Majumdar; Carmen Picón; Jonel Trebicka
    更新日期:2020-01-15
  • Thyroid hormone inhibits hepatocellular carcinoma progression via induction of differentiation and metabolic reprogramming
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Marta Anna Kowalik; Elisabetta Puliga; Lavinia Cabras; Pia Sulas; Annalisa Petrelli; Andrea Perra; Giovanna Maria Ledda-Columbano; Andrea Morandi; Simone Merlin; Claudia Orrù; Carlos Sanchez-Martin; Francesca Fornari; Laura Gramantieri; Matteo Parri; Andrea Rasola; Sara Erika Bellomo; Carlos Sebastian; Antonia Follenzi; Amedeo Columbano
    更新日期:2020-01-15
  • A dual role for hepatocyte-intrinsic canonical NF-κB signaling in virus control
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Sukumar Namineni; Tracy O‘Connor; Suzanne Faure-Dupuy; Pål Johansen; Tobias Riedl; Kaijing Liu; Haifeng Xu; Indrabahadur Singh; Prashant Shinde; Fanghui Li; Aleksandra Pandyra; Piyush Sharma; Marc Ringelhan; Andreas Muschaweckh; Katharina Borst; Patrick Blank; Sandra Lampl; David Durantel; Mathias Heikenwalder
    更新日期:2020-01-15
  • Physical Activity Compared to Adiposity and Risk of Liver-Related Mortality: Results from Two Prospective, Nationwide Cohorts
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Tracey G. Simon; Mi Na Kim; Xiao Luo; Wanshui Yang; Yanan Ma; Dawn Q. Chong; Charles S. Fuchs; Jeffrey A. Meyerhardt; Kathleen E. Corey; Raymond T. Chung; Meir Stampfer; Xuehong Zhang; Edward L. Giovannucci; Andrew T. Chan
    更新日期:2020-01-15
  • DEVELOPMENT OF CHRONIC KIDNEY DISEASE AFTER ACUTE KIDNEY INJURY IN PATIENTS WITH CIRRHOSIS IS COMMON AND IMPAIRS CLINICAL OUTCOMES
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Octavi Bassegoda; Patricia Huelin; Xavier Ariza; Cristina Solé; Adrià Juanola; Jordi Gratacós-Ginès; Marta Carol; Isabel Graupera; Elisa Pose; Laura Napoleone; Sonia Albertos; Gloria de Prada; Marta Cervera; Javier Fernández; Núria Fabrellas; Esteban Poch; Elsa Solà; Pere Ginès
    更新日期:2020-01-15
  • IL-33/ST2 pathway regulates neutrophil migration and predicts outcome in patients with severe alcoholic hepatitis
    J. Hepatol. (IF 18.946) Pub Date : 2020-01-15
    Florent Artru; Mohamed Bou Saleh; François Maggiotto; Guillaume Lassailly; Massih Ningarhari; Julie Demaret; Line-Carolle Ntandja-Wandji; Jean-Paul Pais de Barros; Julien Labreuche; Elodie Drumez; Doumet Georges Helou; Sébastien Dharancy; Emilie Gantier; Axel Périanin; Sylvie Chollet-Martin; Ramon Bataller; Philippe Mathurin; Laurent Dubuquoy; Alexandre Louvet
    更新日期:2020-01-15
  • IL-17 signaling in steatotic hepatocytes and macrophages promotes hepatocellular carcinoma in alcohol-related liver disease
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-31
    Hsiao-Yen Ma; Gen Yamamoto; Jun Xu; Xiao Liu; Daniel Karin; Ju Youn Kim; Ludmil B. Alexandrov; Yukinori Koyama; Takahiro Nishio; Chris Benner; Sven Heinz; Sara B. Rosenthal; Shuang Liang; Mengxi Sun; Gabriel Karin; Peng Zhao; Pnina Brodt; Iain H. Mckillop; Tatiana Kisseleva
    更新日期:2019-12-31
  • OGDHL silencing promotes hepatocellular carcinoma by reprogramming glutamine metabolism
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-30
    W.Q. Dai; L. Xu; X.N. Yu; G.C. Zhang; H.Y. Guo; H.L. Liu; G.Q. Song; S.Q. Weng; L. Dong; J.M. Zhu; T.T. Liu; C.Y. Guo; X.Z. Shen
    更新日期:2019-12-30
  • A randomized, placebo-controlled trial of emricasan in patients with NASH and F1-F3 fibrosis
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-27
    Stephen A. Harrison; Zachary Goodman; Abdul Jabbar; Ravi Vemulapalli; Ziad H. Younes; Bradley Freilich; Muhammad Y. Sheikh; Jörn M. Schattenberg; Zeid Kayali; Adam Zivony; Aasim Sheikh; Javier Garcia-Samaniego; Sanjaya K. Satapathy; George Therapondos; Edward Mena; Detlef Schuppan; James Robinson; Jean L. Chan; Arun J. Sanyal
    更新日期:2019-12-27
  • Heterogeneous immunogenomic features and distinct escape mechanisms in multifocal hepatocellular carcinoma
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-27
    Liang-qing Dong; Li-hua Peng; Li-jie Ma; Dong-bing Liu; Shu Zhang; Shu-zhen Luo; Jun-hua Rao; Hong-wen Zhu; Shuai-xi Yang; Shui-jun Xi; Min Chen; Fan-fan Xie; Fu-qiang Li; Wen-hui Li; Chen Ye; Li-ya Lin; Yu-jue Wang; Xiao-ying Wang; Qiang Gao
    更新日期:2019-12-27
  • Randomized Placebo-Controlled Trial of Emricasan in Non-alcoholic Steatohepatitis (NASH) Cirrhosis with Severe Portal Hypertension
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-21
    Guadalupe Garcia-Tsao; Jaime Bosch; Zeid Kayali; Stephen A. Harrison; Manal F. Abdelmalek; Eric Lawitz; Sanjaya K. Satapathy; Marwan Ghabril; Mitchell L. Shiffman; Ziad H. Younes; Paul J. Thuluvath; Annalisa Berzigotti; Agustin Albillos; James M. Robinson; David T. Hagerty; Jean L. Chan; Arun J. Sanyal
    更新日期:2019-12-21
  • Comparison of extracellular and hepatobiliary MR contrast agents for the diagnosis of small HCCs
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-21
    Anita Paisant; Valérie Vilgrain; Jérémie Riou; Frédéric Oberti; Olivier Sutter; Valérie Laurent; Agnès Rodes; Boris Guiu; Christophe Cassinotto; Hervé Trillaud; Yvan Bricault; Sophie Michalak; Onorina Bruno; Maxime Ronot; Christophe Aubé
    更新日期:2019-12-21
  • Interferon-inducible MX2 is a host restriction factor of hepatitis B virus replication
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-18
    Yong-Xiang Wang; Matthias Niklasch; Tiantian Liu; Yang Wang; Bisheng Shi; Wenjie Yuan; Thomas F. Baumert; Zhenghong Yuan; Shuping Tong; Michael Nassal; Yu-Mei Wen
    更新日期:2019-12-19
  • BAP1 mutations define a homogeneous subgroup of hepatocellular carcinoma with fibrolamellar-like features and activated PKA
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-18
    Théo Z. Hirsch; Ana Negulescu; Barkha Gupta; Stefano Caruso; Bénédicte Noblet; Gabrielle Couchy; Quentin Bayard; Léa Meunier; Guillaume Morcrette; Jean-Yves Scoazec; Jean-Frédéric Blanc; Giuliana Amaddeo; Jean-Charles Nault; Paulette Bioulac-Sage; Marianne Ziol; Aurélie Beaufrère; Valérie Paradis; Julien Calderaro; Jessica Zucman-Rossi
    更新日期:2019-12-18
  • High incidence of HCV in HIV-negative men who have sex with men using pre-exposure prophylaxis
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-18
    Elske Hoornenborg; Liza Coyer; Anders Boyd; Roel Christiaan Alfons Achterbergh; Maarten Franciscus Schim van der Loeff; Sylvia Bruisten; Henry John Christiaan de Vries; Jelle Koopsen; Thijs JW. van de Laar; Maria Prins
    更新日期:2019-12-18
  • Clinical validation of the FLIP algorithm and the SAF score in patients with non-alcoholic fatty liver disease
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-17
    Fabio Nascimbeni; Pierre Bedossa; Larysa Fedchuk; Raluca Pais; Frédéric Charlotte; Pascal Lebray; Thierry Poynard; Vlad Ratziu
    更新日期:2019-12-18
  • Autophagy in hepatic adaptation to stress
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-16
    Younis Hazari; José Manuel Bravo-San Pedro; Claudio Hetz; Lorenzo Galluzzi; Guido Kroemer

    Autophagy is an evolutionarily ancient process whereby eukaryotic cells eliminate disposable or potentially dangerous cytoplasmic material, to support bioenergetic metabolism and adapt to stress. Accumulating evidence indicates that autophagy operates as a critical quality control mechanism for the maintenance of hepatic homeostasis in both parenchymal (hepatocytes) and non-parenchymal (stellate cells, sinusoidal endothelial cells, Kupffer cells) compartments. In line with this notion, insufficient autophagy has been aetiologically involved in the pathogenesis of multiple liver disorders, including alpha-1-antitrypsin deficiency, Wilson disease, non-alcoholic steatohepatitis, liver fibrosis and hepatocellular carcinoma. Here, we critically discuss the importance of functional autophagy for hepatic physiology, as well as the mechanisms whereby defects in autophagy cause liver disease.

    更新日期:2019-12-17
  • Reassessing the accuracy of PAGE-B-related scores to predict hepatocellular carcinoma development in patients with chronic hepatitis B
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-16
    Terry Cheuk-Fung Yip; Grace Lai-Hung Wong; Vincent Wai-Sun Wong; Yee-Kit Tse; Lilian Yan Liang; Vicki Wing-Ki Hui; Hye Won Lee; Grace Chung-Yan Lui; Henry Lik-Yuen Chan
    更新日期:2019-12-17
  • MUC13 promotes intrahepatic cholangiocarcinoma progression via EGFR/PI3K/AKT pathways
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-16
    Tiemin Pei; Fanzheng Meng; Peng Xiao; Jihua Han; Ruipeng Song; Yaliang Lan; Yan Wang; Junlin Xue; Qingfu Lang; Zhefeng He; Jian Li; Zihao Guo; Guoxing Liu; Boshi Sun; Ming Zhao; Qinghui Meng; Desen Liang; Lianxin Liu
    更新日期:2019-12-17
  • ARRB1 inhibits non-alcoholic steatohepatitis progression by promoting GDF15 maturation
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-16
    Zechuan Zhang; Xiaoliang Xu; Wenfang Tian; Runqiu Jiang; Yijun Lu; Qikai Sun; Rao Fu; Qifeng He; Jincheng Wang; Yang Liu; Hailong Yu; Beicheng Sun
    更新日期:2019-12-17
  • Alginate microencapsulated human hepatocytes for the treatment of acute liver failure in children
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-13
    Anil Dhawan; Nataruks Chaijitraruch; Emer Fitzpatrick; Sanjay Bansal; Celine Filippi; Sharon C. Lehec; Nigel D. Heaton; Pauline Kane; Anita Verma; Robin D. Hughes; Ragai R. Mitry
    更新日期:2019-12-17
  • Non-enhanced Magnetic Resonance Imaging as a Surveillance Tool for Hepatocellular Carcinoma: Comparison with Ultrasound
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-10
    Hyo Jung Park, Hye Young Jang, So Yeon Kim, So Jung Lee, Hyung Jin Won, Jae Ho Byun, Sang Hyun Choi, Seung Soo Lee, Jihyun An, Young-Suk Lim
    更新日期:2019-12-11
  • PSMP/MSMP promotes hepatic fibrosis through CCR2 and represents a novel therapeutic target
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-06
    Shaoping She, Xiaoning Wu, Danfeng Zheng, Xiaolei Pei, Jing Ma, Yameng Sun, Jialing Zhou, Lin Nong, Changyuan Guo, Ping Lv, Quansheng Song, Can Zheng, Weiwei Liang, Shiyang Huang, Qingqing Li, Zhongtian Liu, Zhanming Song, Yuzi Li, Ying Wang
    更新日期:2019-12-06
  • Progress and Challenges in a Pioneering Hepatitis C Elimination Program in the Country of Georgia, 2015–2018
    J. Hepatol. (IF 18.946) Pub Date : 2019-12-04
    Francisco Averhoff, Shaun Shadaker, Amiran Gamkrelidze, Tatia Kuchuloria, Lia Gvinjilia, Vladimer Getia, David Sergeenko, Maia Butsashvili, Tengiz Tsertsvadze, Lali Sharvadze, Jaba Zarkua, Beth Skaggs, Muazzam Nasrullah
    更新日期:2019-12-04
  • The chances of hepatic resection curing hepatocellular carcinoma
    J. Hepatol. (IF 18.946) Pub Date : 2019-11-30
    Alessandro Cucchetti, Jianhong Zhong, Sarah Berhane, Hidenori Toyoda, KeQing Shi, Toshifumi Tada, Charing C.N. Chong, Bang-De Xiang, Le-Qun Li, Paul B.S. Lai, Giorgio Ercolani, Vincenzo Mazzaferro, Masatoshi Kudo, Matteo Cescon, Antonio Daniele Pinna, Takashi Kumada, Philip J. Johnson
    更新日期:2019-11-30
  • Evolution of eGFR in chronic HCV patients receiving sofosbuvir-based or sofosbuvir-free direct acting antivirals
    J. Hepatol. (IF 18.946) Pub Date : 2019-11-29
    Chen-Hua Liu, Mei-Hsuan Lee, Jou-Wei Lin, Chun-Jen Liu, Tung-Hung Su, Tai-Chung Tseng, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
    更新日期:2019-11-30
  • Interleukin-22 ameliorates acute-on-chronic liver failure by reprogramming of impaired regeneration pathways in mice
    J. Hepatol. (IF 18.946) Pub Date : 2019-11-29
    Xiaogang Xiang, Dechun Feng, Seonghwan Hwang, Tianyi Ren, Xiaolin Wang, Eszter Trojnar, Csaba Matyas, Ruidong Mo, Dabao Shang, Yong He, Wonhyo Seo, Vijay H. Shah, Pal Pacher, Qing Xie, Bin Gao
    更新日期:2019-11-29
  • B cell immunodominance in primary hepatitis C virus infection
    J. Hepatol. (IF 18.946) Pub Date : 2019-11-28
    Nicholas A. Brasher, Auda A. Eltahla, Alexander Underwood, Irene Boo, Simone Rizzetto, Melanie Walker, Chaturaka Rodrigo, Fabio Luciani, Lisa Maher, Heidi E. Drummer, Nicodemus Tedla, Andrew R. Lloyd, Rowena A. Bull
    更新日期:2019-11-28
  • Hepatitis C reinfection after successful antiviral treatment among people who inject drugs: A meta-analysis
    J. Hepatol. (IF 18.946) Pub Date : 2019-11-27
    Behzad Hajarizadeh, Evan B. Cunningham, Heather Valerio, Marianne Martinello, Matthew Law, Naveed Janjua, Håvard Midgard, Olav Dalgard, John Dillon, Matthew Hickman, Julie Bruneau, Gregory J. Dore, Jason Grebely
    更新日期:2019-11-28
  • Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF
    J. Hepatol. (IF 18.946) Pub Date : 2019-11-25
    Richard Moreau, Joan Clària, Ferran Aguilar, François Fenaille, Juanjo Lozano, Christophe Junot, Benoit Colsch, Paolo Caraceni, Jonel Trebicka, Marco Pavesi, Carlo Alessandria, Frederik Nevens, Faouzi Saliba, Tania M. Welzel, Agustin Albillos, Thierry Gustot, Javier Fernández, Christophe Moreno, Paolo Angeli

    Background & aims Acute-on-chronic liver failure (ACLF), which develops in patients with cirrhosis, is characterized by intense systemic inflammation and organ failure(s). Because systemic inflammation is energetically expensive, its metabolic costs may result in organ dysfunction/failure. Therefore, we aimed to analyze blood metabolome in patients with cirrhosis, with and without ACLF. Methods We performed untargeted metabolomics using liquid chromatography coupled to high-resolution mass spectrometry in serum from 650 patients with AD (acute decompensation of cirrhosis, without ACLF), 181 with ACLF, 43 with compensated cirrhosis, and 29 healthy subjects. Results Of the 137 annotated metabolites identified, 100 were increased in patients with ACLF of any grade, relative to those with AD, and 38 composed a distinctive blood metabolite fingerprint for ACLF. Among patients with ACLF, the intensity of the fingerprint increased across ACLF grades, and was similar in patients with kidney failure and in those without, indicating that the fingerprint reflected not only decreased kidney excretion but also altered cell metabolism. The higher the ACLF-associated fingerprint intensity, the higher plasma levels of inflammatory markers, tumor necrosis factor α, soluble CD206, and soluble CD163. ACLF was characterized by intense proteolysis and lipolysis; amino acid catabolism; extra-mitochondrial glucose metabolism through glycolysis, pentose phosphate, and D-glucuronate pathways; depressed mitochondrial ATP-producing fatty acid β-oxidation; and extra-mitochondrial amino acid metabolism giving rise to metabolites which are metabotoxins. Conclusions In ACLF, intense systemic inflammation is associated with blood metabolite accumulation witnessing profound alterations in major metabolic pathways, in particular inhibition in mitochondrial energy production, which may contribute to the existence of organ failures.

    更新日期:2019-11-26
  • The Phosphatidylethanolamine Biosynthesis Pathway Provides a New Target for Cancer Chemotherapy
    J. Hepatol. (IF 18.946) Pub Date : 2019-11-22
    Yuan Guan, Xinyu Chen, Manhong Wu, Wan Zhu, Ahmed Arslan, Saori Takeda, Mindie H. Nguyen, Ravindra Majeti, Dan Thomas, Ming Zheng, Gary Peltz
    更新日期:2019-11-22
  • Early Acetaminophen-Protein Adducts Predict Hepatotoxicity Following Overdose
    J. Hepatol. (IF 18.946) Pub Date : 2019-11-22
    Angela L. Chiew, Laura P. James, Geoffrey K. Isbister, John W. Pickering, Kylie McArdle, Betty SH. Chan, Nicholas A. Buckley
    更新日期:2019-11-22
  • Inhibition of receptor-interacting protein kinase 1 improves experimental non-alcoholic fatty liver disease
    J. Hepatol. (IF 18.946) Pub Date : 2019-11-21
    Amine Majdi, Lynda Aoudjehane, Vlad Ratziu, Tawhidul Islam, Marta B. Afonso, Filomena Conti, Taïeb Mestiri, Marie Lagouge, Fabienne Foufelle, Florine Ballenghien, Tatiana Ledent, Marthe Moldes, Axelle Cadoret, Laura Fouassier, Jean-Louis Delaunay, Tounsia Aït-Slimane, Gilles Courtois, Bruno Fève, Jérémie Gautheron
    更新日期:2019-11-22
  • Decentralized care with generic direct-acting antivirals in the management of chronic hepatitis C in a public health care setting
    J. Hepatol. (IF 18.946) Pub Date : 2019-07-17
    Radha K. Dhiman, Gagandeep S. Grover, Madhumita Premkumar, Sunil Taneja, Ajay Duseja, Sanjeev Arora, Sahaj Rathi, Sandeep Satsangi, Akash Roy
    更新日期:2019-11-18
  • Hepatitis B virus-induced modulation of liver macrophage function promotes hepatocyte infection
    J. Hepatol. (IF 18.946) Pub Date : 2019-07-23
    Suzanne Faure-Dupuy, Marion Delphin, Ludovic Aillot, Laura Dimier, Fanny Lebossé, Judith Fresquet, Romain Parent, Matthias Sebastian Matter, Michel Rivoire, Nathalie Bendriss-Vermare, Anna Salvetti, Danijela Heide, Lalo Flores, Klaus Klumpp, Angela Lam, Fabien Zoulim, Mathias Heikenwälder, David Durantel, Julie Lucifora
    更新日期:2019-11-18
  • FXR modulates the gut-vascular barrier by regulating the entry sites for bacterial translocation in experimental cirrhosis
    J. Hepatol. (IF 18.946) Pub Date : 2019-07-08
    Marcel Sorribas, Manuel O. Jakob, Bahtiyar Yilmaz, Hai Li, David Stutz, Yannik Noser, Andrea de Gottardi, Sheida Moghadamrad, Moshin Hassan, Agustin Albillos, Ruben Francés, Oriol Juanola, Ilaria Spadoni, Maria Rescigno, Reiner Wiest
    更新日期:2019-11-18
  • Genomic sequencing identifies WNK2 as a driver in hepatocellular carcinoma and a risk factor for early recurrence
    J. Hepatol. (IF 18.946) Pub Date : 2019-07-23
    Shao-Lai Zhou, Zheng-Jun Zhou, Zhi-Qiang Hu, Cheng-Li Song, Yi-Jie Luo, Chu-Bin Luo, Hao-Yang Xin, Xin-Rong Yang, Ying-Hong Shi, Zheng Wang, Xiao-Wu Huang, Ya Cao, Jia Fan, Jian Zhou
    更新日期:2019-11-18
  • The Candida albicans exotoxin Candidalysin promotes alcohol-associated liver disease
    J. Hepatol. (IF 18.946) Pub Date : 2019-10-10
    Huikuan Chu, Yi Duan, Sonja Lang, Lu Jiang, Yanhan Wang, Cristina Llorente, Jinyuan Liu, Selene Mogavero, Francisco Bosques-Padilla, Juan G. Abraldes, Victor Vargas, Xin M. Tu, Ling Yang, Xiaohua Hou, Bernhard Hube, Peter Stärkel, Bernd Schnabl
    更新日期:2019-11-18
  • Comparative characterization of B cells specific for HBV nucleocapsid and envelope proteins in patients with chronic hepatitis B
    J. Hepatol. (IF 18.946) Pub Date : 2019-07-23
    Nina Le Bert, Loghman Salimzadeh, Upkar Singh Gill, Charles-Antoine Dutertre, Floriana Facchetti, Anthony Tan, Magdeleine Hung, Nikolai Novikov, Pietro Lampertico, Simon Paul Fletcher, Patrick Thomas Francis Kennedy, Antonio Bertoletti
    更新日期:2019-11-18
  • Chronic hyperammonemia induces peripheral inflammation that leads to cognitive impairment in rats: reversal by anti-tnfa treatment
    J. Hepatol. (IF 18.946) Pub Date : 2019-01-14
    Tiziano Balzano, Sherry Dadsetan, Jerónimo Forteza, Andrea Cabrera-Pastor, Lucas Taoro-Gonzalez, Michele Malaguarnera, Sara Gil-Perotin, Laura Cubas-Nuñez, Bonaventura Casanova, Agueda Castro-Quintas, Alejandro Ponce-Mora, Yaiza M Arenas, Paola Leone, Marta Llansola, Vicente Felipo
    更新日期:2019-11-18
  • A schistosome miRNA promotes host hepatic fibrosis by targeting transforming growth factor beta receptor III
    J. Hepatol. (IF 18.946) Pub Date : 2019-11-16
    Xing He, Yange Wang, Xiaobin Fan, Nanhang Lei, Yini Tian, Dongmei Zhang, Weiqing Pan
    更新日期:2019-11-17
  • Educate, Test and Treat Model towards elimination of hepatitis C infection in Egypt: Feasibility and effectiveness in 73 villages
    J. Hepatol. (IF 18.946) Pub Date : 2019-11-14
    Gamal Shiha, Reham Soliman, Nabiel NH. Mikhail, Philippa Easterbrook
    更新日期:2019-11-14
  • Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference
    J. Hepatol. (IF 18.946) Pub Date : 2019-11-12
    Markus Cornberg, Anna Suk-Fong Lok, Norah A. Terrault, Fabien Zoulim

    Representatives from academia, industry, regulatory agencies, and patient groups convened in March 2019 with the primary goal of developing agreement on chronic hepatitis B virus (HBV) treatment endpoints to guide clinical trials aiming to ‘cure’ HBV. Agreement among the conference participants was reached on some key points. ‘Functional’ but not sterilizing cure is achievable and should be defined as sustained HBsAg loss in addition to undetectable HBV DNA 6 months post-treatment. The primary endpoint of phase 3 trials should be functional cure; HBsAg loss in ≥30% of patients was suggested as an acceptable rate of response in these trials. Sustained virologic suppression (undetectable serum HBV DNA) without HBsAg loss, 6 months after discontinuation of treatment would be an intermediate goal. Demonstrated validity in predicting sustained HBsAg loss was considered the most appropriate criterion for the approval of new HBV assays to determine efficacy endpoints. Clinical trials aimed at HBV functional cure should initially focus on patients with HBeAg-positive and HBeAg-negative chronic hepatitis, treatment-naïve or virally suppressed on nucleos(t)ide analogues. A hepatitis flare associated with increase in bilirubin or INR should prompt temporary or permanent cessation of investigational treatment. New treatments must be as safe as existing nucleos(t)ide analogues. The primary endpoint for phase 3 trials for hepatitis D virus (HDV) co-infection should be undetectable serum HDV RNA 6 months after stopping treatment. On treatment HDV RNA suppression associated with normalization of ALT is considered an intermediate goal. Conclusion: For HBV ‘functional cure’, sustained HBsAg loss with undetectable HBV DNA after completion of treatment is the primary goal and sustained undetectable HBV DNA without HBsAg loss after stopping treatment an intermediate goal.

    更新日期:2019-11-13
  • Prevalence, features and predictive factors of liver nodules in Fontan surgery patients: The VALDIG Fonliver prospective cohort
    J. Hepatol. (IF 18.946) Pub Date : 2019-11-11
    Luis Téllez, Enrique Rodríguez de Santiago, Beatriz Minguez, Audrey Payance, Ana Clemente, Anna Baiges, Dalia Morales-Arraez, Vincenzo La Mura, Elba Llop, Elena Garrido, Elvira Garrido-Lestache, Stephanie Tasayco, Onorina Bruno, Raquel Prieto, Silvia Montserrat, Mónica Pons, Andreína Olavarría, Laura Dos, Marta Magaz
    更新日期:2019-11-13
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