Plasma and ascites pharmacokinetic of meropenem in patients with decompensated liver cirrhosis and spontaneous bacterial peritonitis
With great interest, we read the study of Wong et al. who investigated risk factors for an acute-on-chronic liver failure (ACLF) in patients with decompensated liver cirrhosis and bacterial infections. Spontaneous bacterial peritonitis (SBP) was the most frequent site of infection and an independent risk factor for ACLF development. Moreover, ACLF was more common in patients infected with multidrug resistant bacteria (MDRB) and those with an insufficient response to the initial antibiotic treatment. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 23, 2021 Category: Gastroenterology Authors: Marie Schultalbers, Denis Grote-Koska, Markus Cornberg, Julius J. Schmidt, Benjamin Maasoumy, CirPK - Study Group Tags: Letter to the Editor Source Type: research

Decision making in systemic therapy of hepatocellular carcinoma: should we pay attention to disease etiology?
Both authors wrote the manuscript. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 22, 2021 Category: Gastroenterology Authors: Peter R. Galle, Ghassan Abou-Alfa Tags: Editorial Source Type: research

Prognostic value of histologic parameters in alcoholic hepatitis: a word of caution
The authors declare they have no competing interests (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 20, 2021 Category: Gastroenterology Authors: Pierre Deltenre, Astrid Marot Tags: Letter to the Editor Source Type: research

Reply to Huang et. al. [JHEPAT-D-19-00400R1]
In this issue of the Journal of Hepatology, Huang and colleagues report the successful treatment of 105 Asian patients on hemodialysis using 12 weeks of sofosbuvir/velpatasvir in whom 9 randomly selected patients had serum levels of the predominant sofosbuvir metabolite GS-331007 measured at weeks 4, 8 and 12 of treatment and weeks 4, 12 and 52 post treatment. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 19, 2021 Category: Gastroenterology Authors: Sergio M. Borgia, Stephen D. Shafran Tags: Letter to the Editor Source Type: research

Association of chronic liver disease with the prognosis of COVID-19 patients
We read with interest the recent work in the Journal of Hepatology by Mallet et al., who studied the outcomes, including mechanical ventilation and day-30 mortality, of all coronavirus disease 2019 (COVID-19) adult patients (N = 259,110) discharged from acute and post-acute care and private and public hospitals in France in 2020.1 Their results suggested that chronic liver disease increases the risk of COVID-19 death. However, there are some issues that need to be addressed to ensure that the results of this study are more convincing and therefore contribute to further investigations exploring the risk of death after COVID...
Source: Journal of Hepatology - July 18, 2021 Category: Gastroenterology Authors: Junyu Long, Xinting Sang, Haitao Zhao Tags: Letter to the Editor Source Type: research

Maternal obesity increases the risk and severity of NAFLD in offspring
Maternal obesity has been linked to the development of cardiovascular disease and diabetes in offspring, but its relationship to non-alcoholic fatty liver disease (NAFLD) is unclear. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 18, 2021 Category: Gastroenterology Authors: Hannes Hagstr öm, Tracey G. Simon, Bjorn Roelstraete, Olof Stephansson, Jonas Söderling, Jonas F. Ludvigsson Source Type: research

SARS-CoV-2-specific immunity in immunosuppressed COVID-19 convalescents with autoimmune hepatitis
We read with interest the article “SARS-CoV-2 infection in patients with autoimmune Hepatitis” by Marjot et al. [1] recently published in the Journal of hepatology. While immunosuppressive therapy for autoimmune hepatitis (AIH) had no negative impact on the immediate outcome of COVID-19 [1-3], the question remained, whether COVI D-19 convalescents immunosuppressed for AIH (AIH-Con) are protected from a SARS-CoV-2 reinfection as non-immunosuppressed convalescents (non-IS-Con). (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 17, 2021 Category: Gastroenterology Authors: Theresa Kirchner, Elmar Jaeckel, Christine S. Falk, Britta Eiz-Vesper, Richard Taubert Tags: Letter to the Editor Source Type: research

Editorial Board
(Source: Journal of Hepatology)
Source: Journal of Hepatology - July 16, 2021 Category: Gastroenterology Source Type: research

Register now with early fees for the Digital NAFLD Summit 2021
(Source: Journal of Hepatology)
Source: Journal of Hepatology - July 16, 2021 Category: Gastroenterology Source Type: research

Discover the new event “Bleeding, Thrombosis & Vascular Liver Diseases ” coming up on 7–9 October
(Source: Journal of Hepatology)
Source: Journal of Hepatology - July 16, 2021 Category: Gastroenterology Source Type: research

Register now for the EASL –AASLD HCC Endpoints event on 28–29 October
(Source: Journal of Hepatology)
Source: Journal of Hepatology - July 16, 2021 Category: Gastroenterology Source Type: research

Visit EASL Campus & discover 4,100 + resources on hepatology & liver-related research
(Source: Journal of Hepatology)
Source: Journal of Hepatology - July 16, 2021 Category: Gastroenterology Source Type: research

Contents
(Source: Journal of Hepatology)
Source: Journal of Hepatology - July 16, 2021 Category: Gastroenterology Source Type: research

JHEP at a glance (August 2021)
(Source: Journal of Hepatology)
Source: Journal of Hepatology - July 16, 2021 Category: Gastroenterology Source Type: research

From the Editor ’s Desk…
Despite the large number of clinical trials on COVID-19 vaccines, only a few participants with pre-existing liver diseases were included. In this issue of the Journal, 2 separate studies analyse the safety and efficacy of COVID-19 vaccines in patients with non-alcoholic fatty liver disease (NAFLD) and in liver transplant recipients. Wang et  al. reported that neutralising antibodies against SARS-CoV-were detected in 364 (95.5%) patients with NAFLD, based on an analysis of the CHESS2101 study from China. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 16, 2021 Category: Gastroenterology Authors: Patrizia Burra, Frank Tacke, Vlad Ratziu, Stefan Zeuzem, Bruno Sangro, Paolo Angeli Tags: From the Editor's Desk Source Type: research

Reply to JHEPAT-D-21-00702 and JHEPAT-D-21-00793
Firstly, the authors would like to thank Dr. Sundaram1 and Dr. Fischer et al2 for their interest in our paper.3 We also want to thank Dr. Fischer for providing some local data on a subgroup of patients with cirrhosis who were admitted into intensive care unit (ICU). Comparing their patients to the entire group of the patients in the global study, Dr. Fischer ’s patients were a lot sicker, by virtue of the fact that they required ICU care. Many of them had multiple complications of cirrhosis, multiple infection sites, many more of nosocomial infections which are usually associated with a worse outcome,4 had a higher q...
Source: Journal of Hepatology - July 16, 2021 Category: Gastroenterology Authors: Florence Wong, Salvatore Piano, Paolo Angeli Tags: Letter to the Editor Source Type: research

Reply to ‘Ceruloplasmin Variants Might Have Different Effects in Different Iron Overload Disorders’
We greatly appreciated the Letter by S. Pelucchi et al.1 commenting on our paper on the impact of ceruloplasmin (CP) gene variation on hepatic iron deposition and liver damage in patients with nonalcoholic fatty liver disease (NAFLD).2 The authors presented novel functional data suggesting that the low-frequency rs61733458 (p.Thr551Ile) CP variant determines a loss-of-function of ceruloplasmin.1 These data are in agreement with a role of this variant in favouring liver iron deposition as suggested by our work. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 15, 2021 Category: Gastroenterology Authors: Elena Corradini, Luca Vittorio Valenti Tags: Letter to the Editor Source Type: research

Unraveling the role of liver sinusoidal endothelial cells in COVID-19 liver injury
Liver injury is common during SARS-CoV-2 infection. Abnormalities in liver tests can be found in up to 50% of infected patients [1]. In most cases, COVID-19 liver test perturbations consist mainly in liver aminotransferase elevation and correlate with disease severity defined as ICU admission and mortality [2, 3]. Liver injury is generally mild and does not lead to liver failure in patients without advanced liver disease. Patients with decompensated cirrhosis, however, have a significant risk of develop acute-on-chronic liver failure [4]. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 14, 2021 Category: Gastroenterology Authors: Antonio Saviano, Thomas F. Baumert Tags: Editorial Source Type: research

Fibrogenic signals persist in DAA-treated HCV patients after sustained virological response
HCV SVR, achievable now by means of DAA therapy, identifies a new class of patients requiring medical surveillance to be designed in relation to the liver disease stage advancement. To this end, identification of both disease biomarkers and therapeutic targets appears necessary. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 13, 2021 Category: Gastroenterology Authors: Claudia Montaldo, Michela Terri, Veronica Riccioni, Cecilia Battistelli, Veronica Bordoni, Gianpiero D ’Offizi, Maria Giulia Prado, Flavia Trionfetti, Tiziana Vescovo, Eleonora Tartaglia, Raffaele Strippoli, Chiara Agrati, Marco Tripodi Source Type: research

Predicting survival after TIPS: Child Pugh Score is not inferior to MELD and FIPS Score – back to basics?
With great interest, we read the publication by Bettinger et al. who reported a newly developed survival prognosis score for patients after transjugular intrahepatic portosystemic shunt (TIPS) – the Freiburg index for post TIPS Survival (FIPS).1 In their multi-center cohort, the FIPS score showed a better survival prediction after TIPS implantation than widely known and used prognosis scores that means the Child-Pugh and MELD score. When Kraglund et al. tried to validate the FIPS score in an independent patient cohort of 104 patients,2 the Child-Pugh was not inferior in prognosis prediction than the MELD and FIPS sco...
Source: Journal of Hepatology - July 12, 2021 Category: Gastroenterology Authors: Julian Pohl, Bernhard Gebauer, Pimrapat Gebert, Frank Tacke, Alexander Wree Tags: Letter to the Editor Source Type: research

Hemochromatoses
In the field of chronic iron overload diseases, hemochromatoses are genetic diseases where iron overload is caused by hepcidin deficiency and, much more rarely, by hepcidin resistance. These disorders are related to mutations of HFE or non-HFE genes that are involved in the control of hepcidin expression or bioactivity, which tunes systemic iron homeostasis.1 (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 11, 2021 Category: Gastroenterology Authors: Pierre Brissot, Olivier Lor éal Tags: Hepatology Snapshot Source Type: research

Systemic treatment of hepatocellular carcinoma. An EASL position paper.
The last five years have witnessed relevant advances in the systemic therapy of hepatocellular carcinoma. New data have emerged since the development of the EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma in 2018. Drugs licensed in some countries now include four oral multi-tyrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib and cabozantinib), one antiangiogenic antibody (ramucirumab) and four immune checkpoint inhibitors, alone or in combination (atezolizumab in combination with bevacizumab, ipilimumab in combination with nivolumab, nivolumab and pembrolizumab in monotherapy). (S...
Source: Journal of Hepatology - July 10, 2021 Category: Gastroenterology Authors: Jordi Bruix, Stephen L. Chan, Peter R. Galle, Lorenza Rimassa, Bruno Sangro Tags: Position Paper Source Type: research

AN ANUSUAL CASE OF ACUTE CHOLESTATIC HEPATITIS AFTER m-RNABNT162b2 (COMIRNATY) SARS-CoV-2 VACCINE: COINCIDENCE, AUTOIMMUNITY OR DRUG RELATED LIVER INJURY?
Francesca Lodato: patient ’s care, writing of the manuscript and revision of the final version of the manuscript. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 10, 2021 Category: Gastroenterology Authors: Francesca Lodato, Anna Larocca, Antonietta D ’Errico, Vincenzo Cennamo Tags: Letter to the Editor Source Type: research

Deciphering FAK in intrahepatic cholangiocarcinoma: a novel therapeutic target?
Almost 40 years ago, an intracellular kinase was identified in cellular focal adhesions and thus named Focal Adhesion Kinase (FAK).[1, 2] FAK, encoded by the gene PTK2, is a cytoplasmic protein tyrosine kinase required in several tissues for normal development.[3] Since its discovery, it has been pinpointed as an essential protein for the progression of different human diseases acting as a key signalling component that relays diverse extracellular stimuli to regulate cell motility.[3] Over the last decades it was shown that FAK is overexpressed and activated in several solid cancers and acts as a crucial player in tumorige...
Source: Journal of Hepatology - July 9, 2021 Category: Gastroenterology Authors: Javier Vaquero, Verena Keitel Tags: Editorial Source Type: research

The reply to the correspondence entitled “Understanding HBcrAg components helps the better interpretation of clinical HBcrAg assay results” by Hong, X. and Hu, J.
We thank Hong and Hu [1] for their interest in our article [2] and we also thank the Journal of Hepatology for the opportunity to reply to their thoughtful discussion on the nature of HBcrAg. We appreciate them for their questions, but the discussion does not influence on our major conclusion that the novel high-sensitivity HBcrAg quantitative assay, iTACT-HBcrAg, could be useful to monitor responses in HBeAg-negative patients and detect HBV reactivation. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 8, 2021 Category: Gastroenterology Authors: Takako Inoue, Shintaro Yagi, Yasuhito Tanaka Tags: Letter to the Editor Source Type: research

Universal definition and prognostication in acute-on-chronic liver failure – an unmet need!
We read the study by Li and Thuluvath (1) with great interest that highlighted the differences in prevalence and mortality between acute-on-chronic liver failure (ACLF) defined by the North American Consortium for the study of End-stage Liver Disease (NACSELD) (2) and the European Association for the Study of the Liver – Chronic Liver Failure Consortium (EASL-CLIF) (3) criteria. The authors conclude that EASL-CLIF criterion is better than NACSELD criteria in detection and prognostication of ACLF. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 8, 2021 Category: Gastroenterology Authors: Nipun Verma, Rohit Mehtani, Ajay Duseja Tags: Letter to the Editor Source Type: research

I shall be released (from infinite HBV nucleos(t)ide analog therapy): Japanese experience
ME: writing the draft; TU and FS: critical revision. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 7, 2021 Category: Gastroenterology Authors: Masaru Enomoto, Takeji Umemura, Fumitaka Suzuki Tags: Letter to the Editor Source Type: research

Untargeted lipidomics uncovers lipid signatures distinguishing severe versus moderate forms of acutely decompensated cirrhosis
Acutely decompensated of cirrhosis is a heterogeneous clinical entity associated with moderate mortality. In some patients, this condition develops quickly into a more often deadly acute-on-chronic liver failure (ACLF), in which other organs such as the kidneys or brain fail. The aim of this study was to characterize the blood lipidome in a large series of patients with cirrhosis and identify specific signatures associated with acute decompensation and ACLF development. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 7, 2021 Category: Gastroenterology Authors: Joan Cl ària, Anna Curto, Richard Moreau, Benoit Colsch, Cristina López-Vicario, Juan José Lozano, Ferran Aguilar, Florence A. Castelli, François Fenaille, Christophe Junot, Ingrid Zhang, Maria Vinaixa, Oscar Yanes, Paolo Caraceni, Jonel Trebicka, Jav Source Type: research

The mRNA COVID-19 vaccine – a rare trigger of Autoimmune Hepatitis?
We read with interest the letters “Autoimmune hepatitis developing after coronavirus disease 2019 (COVID-19) Vaccine: Causality or casualty?” by Bril et al.1 and “Autoimmune hepatitis following sars-cov-2 VACCINE: MAY not be a casualty” by Rocco et al2 which highlight the hypothesis that COVID-19 mRNA-based vaccines might in crease the risk of developing autoimmune diseases. There are growing reports of autoimmune diseases developing after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, including Guillain-Barré syndrome and Primary Biliary Cholangitis3. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 7, 2021 Category: Gastroenterology Authors: Cathy McShane, Clifford Kiat, Jonathan Rigby, Órla Crosbie Tags: Letter to the Editor Source Type: research

Reply to: “TIPS and liver transplantation should always be discussed together”
With great interest, we read the letter by Rudler et  al. focusing on the Freiburg index of post-TIPS survival (FIPS) score in the setting of liver transplantation (LT).1,2 This example of a multidisciplinary TIPS/LT board is an important step towards personalized treatment of patients with advanced cirrhosis and may serve as a model for other center s. The authors also analyzed the application of the FIPS score in this approach and they were able to show that the FIPS score adequately selects patients who need LT. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 6, 2021 Category: Gastroenterology Authors: Dominik Bettinger, Robert Thimme, Michael Schultheiss Tags: Letter to the Editor Source Type: research

24-NorUrsodeoxycholic acid reshapes immunometabolism in CD8+ T-cells and alleviates hepatic inflammation
24-NorUrsodeoxycholic acid (NorUDCA) is a novel therapeutic bile acid for immune-mediated cholestatic liver diseases, such as primary sclerosing cholangitis (PSC) where dysregulated T-cells including CD8+ T-cells contribute to hepatobiliary immunopathology. We hypothesized that NorUDCA may directly modulate CD8+ T-cell function thus contributing to its therapeutic efficacy. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 6, 2021 Category: Gastroenterology Authors: Ci Zhu, Nicole Boucheron, Andr é C. Müller, Peter Májek, Thierry Claudel, Emina Halilbasic, Hatoon Baazim, Alexander Lercher, Csilla Viczenczova, Daniela Hainberger, Teresa Preglej, Lisa Sandner, Marlis Alteneder, Alexandra F. Gülich, Matarr Khan, Pat Source Type: research

T cells and monocyte-derived myeloid cells mediate immunotherapy-related hepatitis in a mouse model
Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs) which are more severe when ICIs are used in combination. We aim to use a mouse model to elucidate the immune related molecular mechanisms of hepatitis, one of the common ICI irAEs. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 6, 2021 Category: Gastroenterology Authors: Heather P. Llewellyn, Seda Arat, Jingjin Gao, Ji Wen, Shuhua Xia, Dalia Kalabat, Elias Oziolor, Richard Virgen-Slane, Timothy Affolter, Changhua Ji Source Type: research

Novel function of SART1 in HNF4 α transcriptional regulation contributes to its antiviral role during HBV infection
Our understanding about the interaction of the Hepatitis B virus (HBV) with its host cells is still quite limited. Spliceosome associated factor 1 (SART1) has recently been found to restrict Hepatitis C Virus. We aim to dissect its role in HBV infection that remains a big threat to global health. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 6, 2021 Category: Gastroenterology Authors: Yan Teng, Zaichao Xu, Kaitao Zhao, Youquan Zhong, Jingjing Wang, Li Zhao, Zhixin Zheng, Wei Hou, Chengliang Zhu, Xinwen Chen, Ulrike Protzer, Yong Li, Yuchen Xia Source Type: research

The multifaceted role of cathepsins in liver disease
Proteases are the most abundant enzyme gene family in vertebrates and execute essential functions in all living organisms. Their main role is to hydrolase the peptide bond within proteins, a process also called proteolysis. Contrary to the conventional paradigm, proteases are not only random catalytic devices, but can perform highly selective and targeted cleavage of specific substrates, finely modulating multiple essential cellular processes. Lysosomal protease cathepsins comprise three families of proteases with preferential activity within acidic cellular compartments but can also be found in other cellular locations. (...
Source: Journal of Hepatology - July 6, 2021 Category: Gastroenterology Authors: Paloma Ruiz-Bl ázquez, Valeria Pistorio, María Fernández-Fernández, Anna Moles Tags: Focused Review Source Type: research

The Search For Optimum Thiopurine Metabolite Levels in Autoimmune Hepatitis Continues …
We read with great interest the article by Candels et al. who concluded that measuring thiopurine metabolites (TMs) in autoimmune hepatitis (AIH) improves rates of biochemical response (BR) compared to subjects who were given azathioprine (AZA)/6-mercaptopurine (6MP) on a weight-based regimen (77% vs. 60%, p=0.008).(1) But it is unclear how they arrived at this conclusion. They evaluated two cohorts of patients: group1, in whom metabolite testing was performed at least once (n=109), and group2, without any metabolite testing (n=105). (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 6, 2021 Category: Gastroenterology Authors: Rishi Bolia, Anshu Srivastava Tags: Letter to the Editor Source Type: research

Reply: TIPS and liver transplantation should always be discussed together.
Drafting the manuscript: DB, MS. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 6, 2021 Category: Gastroenterology Authors: Dominik Bettinger, Robert Thimme, Michael Schultheiss Tags: Letter to the Editor Source Type: research

Risk factors and screening intervals are crucial to evaluating the cost effectiveness of abbreviated MRI in HCC screening
We read with interest the study by Gupta and colleagues who performed the first systematic review and meta-analysis on the diagnostic performance of different abbreviated MRI protocols for hepatocellular carcinomas screening.(1) They concluded firstly, that the diagnostic performance of abbreviated MRI (AMRI) is substantially higher than ultrasound for early and very early HCC compared with ultrasound, and secondly, that the non-invasive nature, reduced cost, and high sensitivity makes non-contrast abbreviated MRI (NC- AMRI) the ideal AMRI protocol for HCC screening. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 6, 2021 Category: Gastroenterology Authors: Numan Kutaiba, Zaid Ardalan Tags: Letter to the Editor Source Type: research

Before we can find an evidence base for HCC surveillance, we need to define our target demographic
No conflict of interest (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 6, 2021 Category: Gastroenterology Authors: Charmaine Matthews, Timothy JS. Cross Tags: Letter to the Editor Source Type: research

Successful management of refractory ascites in non-TIPSable patients using percutaneous thoracic duct stenting
The standard treatment of refractory ascites in cirrhotic patients relies on TIPS or liver transplantation (LT) 1. When these approaches are contra-indicated, management is based on repeated paracenteses, resulting in poor prognosis and altered quality of life. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 5, 2021 Category: Gastroenterology Authors: Julien Ghelfi, Bleuenn Brusset, Frederic Thony, Thomas Decaens Tags: Letter to the Editor Source Type: research

Androgen receptor, neovascularization and liver cancer metastasis
The mechanisms underlying the recurrence and metastasis of hepatocellular carcinoma (HCC) are poorly understood. In 2015, Zhuang and her colleagues identified a unique histopathological structure in HCC tissues, which they dubbed VETC, standing for vessels that encapsulate tumor clusters.1 In the VETC structure, sinusoid-like vessels form a cobweb-like network that encapsulates individual tumor cell clusters. These endothelium-wrapped tumor cell clusters were released into the blood stream and formed metastatic tumors in a manner independent of epithelial-mesenchymal transition (EMT), another well-known tumor metastatic pr...
Source: Journal of Hepatology - July 4, 2021 Category: Gastroenterology Authors: Morgan W. Feng, Kaisa L. Hanley, Gen-Sheng Feng Tags: Editorial Source Type: research

Reply to: correspondence regarding “Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction”
We greatly appreciate the comments of Professor Avolio and colleagues1 and Professor Eerola and colleagues2 in response to our international, multicenter validation of the L-GrAFT score3 as a measure of early allograft dysfunction following LT. Eerola and colleagues have raised the extremely important issue of having an unequivocal formula for the calculation of L-GrAFT, as rounding of the coefficients to 3 decimal points, particularly for the squared terms, may dramatically alter the calculated risk score. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 3, 2021 Category: Gastroenterology Authors: Vatche G. Agopian, Daniela Markovic Tags: Letter to the Editor Source Type: research

Acute-on-chronic liver failure: a complex clinical entity in patients with autoimmune hepatitis
In their comprehensive and stimulating review, Moreau et al. report the distinctive features of “acute-on-chronic liver failure” (ACLF) based on different geographic definitions (European, North American, Chinese, Asian Pacific) and suggest that ACLF should be considered a unique clinical syndrome.1 However, in discussing hallmarks, causes and precipitating factors of ACLF, they do not con sider the case of autoimmune hepatitis (AIH), which can initiate as acute hepatitis in more than 40% of cases2. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 3, 2021 Category: Gastroenterology Authors: Alessandro Granito, Paolo Muratori, Luigi Muratori Tags: Letter to the Editor Source Type: research

Reply to: “Non-selective beta blockers and mortality in decompensated cirrhosis: Is cirrhotic cardiomyopathy the missing link?”
We thank Izzy and colleagues for the interest in our study and greatly appreciate their interesting suggestions. We agree with them on the relevance of investigating cirrhotic cardiomyopathy (CCM) using the new echocardiographic criteria,1 to ascertain whether patients with CCM based on these criteria have greater risk of detrimental effects from beta-blockade. However, we do not think that performing such an assessment on our data may be of value, given the high risk of bias. During the last 4 years of the study, we only performed TDI-echocardiography in a subgroup of 43 decompensated patients (15 of them with cardiac out...
Source: Journal of Hepatology - July 2, 2021 Category: Gastroenterology Authors: Edilmar Alvarado-Tapias, David Vilades, Anna Brujats, C àndid Villanueva Tags: Letter to the Editor Source Type: research

Polyploidy control in hepatic health and disease
A balanced increase in DNA-content (ploidy) is observed in some human cell types, including bone-resorbing osteoclasts, platelet-producing megakaryocytes, cardiomyocytes or hepatocytes. The impact of increased ploidy in hepatocytes for normal physiology and diverse liver pathologies is still poorly understood. Recent findings suggest swift genetic adaptation to hepatotoxic stress and the protection from malignant transformation as beneficial effects. Here, we discuss the molecular mechanisms regulating hepatocyte polyploidization in its implication for different liver diseases and hepatocellular carcinoma (HCC). (Source: J...
Source: Journal of Hepatology - July 2, 2021 Category: Gastroenterology Authors: Valentina C. Sladky, Felix Eichin, Thomas Reiberger, Andreas Villunger Tags: Review Source Type: research

Multiple investigations for a very common disorder: finding the right balance in NAFLD
Liebe et al ’s excellent and comprehensive review of secondary causes for NAFLD raised important question for the diagnostician.1 How far do we go to find unusual conditions when the data available points to a very common one. As the American physician Theodore Woodward said in the 1940s, ‘When you hear hoo fbeats behind you, don't expect to see a zebra’. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 2, 2021 Category: Gastroenterology Authors: Sreelakshmi Kotha, Philip Berry Tags: Letter to the Editor Source Type: research

Reply letter to correspondence entitled: “Non-selective beta blockers and mortality in decompensated Cirrhosis: Is Cirrhotic Cardiomyopathy the missing link?”
None. (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 2, 2021 Category: Gastroenterology Authors: Edilmar Alvarado-Tapias, David Vilades, Anna Brujats, C àndid Villanueva Tags: Letter to the Editor Source Type: research

Non-alcoholic fatty liver disease in children and young adults is associated with increased long-term mortality
Longitudinal data are scarce regarding the natural history and long-term risk of mortality, in children and young adults with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD). (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 2, 2021 Category: Gastroenterology Authors: Tracey G. Simon, Bjorn Roelstraete, Kayla Hartjes, Uzma Shah, Hamed Khalili, Henrik Arnell, Jonas F. Ludvigsson Source Type: research

DNMT1-mediated methylation of BEX1 regulates stemness and tumorigenicity in liver cancer
Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) exhibit remarkable cancer stem cell (CSCs) features. Moreover, the development of both diseases is closely associated with the presence of CSCs. We investigated the role of brain-expressed X-linked protein 1 (BEX1) in regulating CSC properties of HB, and a subtype of HCC with high CSC features (CSC-HCC). (Source: Journal of Hepatology)
Source: Journal of Hepatology - July 1, 2021 Category: Gastroenterology Authors: Qian Wang, Ning Liang, Tao Yang, Yuedan Li, Jing Li, Qian Huang, Chen Wu, Ligang Sun, Xile Zhou, Xiaobin Cheng, Long Zhao, Gang Wang, Zhangqian Chen, Xianli He, Chaoxu Liu Source Type: research

Medical therapies for intra-hepatic cholangiocarcinoma
Cholangiocarcinoma (CCA) is a heterogeneous group of cancers arising from the biliary tree. Intrahepatic CCA (iCCA) arise from biliary ducts within the hepatic parenchyma, anatomically above second-order bile ducts,1 and have been increasing in global incidence over the last few decades. Less than 30% of iCCAs are resectable at diagnosis and most patients require systemic therapy. Advances in understanding the diverse genetic and molecular signatures of CCA have identified novel targets for cancer-specific therapy. (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 30, 2021 Category: Gastroenterology Authors: Mathew Vithayathil, John Bridegwater, Shahid A. Khan Tags: Hepatology Snapshot Source Type: research

Single-cell atlas of tumor cell evolution in response to therapy in hepatocellular carcinoma and intrahepatic cholangiocarcinoma
Intratumor molecular heterogeneity is a key feature of tumorigenesis and is linked to treatment failure and patient prognosis. Here, we aimed to determine what drives tumor cell evolution by performing single-cell transcriptomic analysis. (Source: Journal of Hepatology)
Source: Journal of Hepatology - June 30, 2021 Category: Gastroenterology Authors: Lichun Ma, Limin Wang, Subreen A. Khatib, Ching-Wen Chang, Sophia Heinrich, Dana A. Dominguez, Marshonna Forgues, Juli án Candia, Maria O. Hernandez, Michael Kelly, Yongmei Zhao, Bao Tran, Jonathan M. Hernandez, Jeremy L. Davis, David E. Kleiner, Bradfor Source Type: research