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Hepatology Communications

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https://www.readbyqxmd.com/read/29761175/anti-tumoral-effects-of-exercise-on-hepatocellular-carcinoma-growth
#1
Uttara Saran, Maria Guarino, Sarai Rodríguez, Cedric Simillion, Matteo Montani, Michelangelo Foti, Bostjan Humar, Marie V St-Pierre, Jean-François Dufour
Regular physical exercise has many beneficial effects, including antitumor properties, and is associated with a reduced risk of developing hepatocellular carcinoma (HCC). Less is known about the impact of exercise on HCC growth and progression. Here, we investigated the effects of exercise on HCC progression and assessed whether any beneficial effects would be evident under sorafenib treatment and could be mimicked by metformin. American Cancer Institute rats with orthotopic syngeneic HCC derived from Morris Hepatoma-3924A cells were randomly assigned to exercise (Exe) and sedentary groups, or sorafenib±Exe groups or sorafenib±metformin groups...
May 2018: Hepatology communications
https://www.readbyqxmd.com/read/29761174/elbasvir-grazoprevir-in-asia-pacific-russian-participants-with-chronic-hepatitis-c-virus-genotype-1-4-or-6-infection
#2
Jacob George, Eduard Burnevich, I-Shyan Sheen, Jeong Heo, Nguyen Van Kinh, Tawesak Tanwandee, Pin-Nan Cheng, Do Young Kim, Won Young Tak, Svetlana Kizhlo, Konstantin Zhdanov, Vasily Isakov, Liwen Liang, Pauline Lindore, Joy Ginanni, Bach-Yen Nguyen, Janice Wahl, Eliav Barr, Michael Robertson, Paul Ingravallo, Rohit Talwani
The prevalence of hepatitis C virus (HCV) infection in Asian countries is high. This study assessed the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from Asia-Pacific countries and Russia. In this phase 3, randomized, placebo-controlled, double-blind study, treatment-naive participants with HCV genotype (GT) 1, 4, or 6 infection were randomized to EBR 50 mg/GZR 100 mg (immediate-treatment group [ITG]) or placebo (deferred-treatment group [DTG]) once daily for 12 weeks (Protocol PN-5172-067, NCT02251990)...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29761173/liver-enriched-transcription-factor-expression-relates-to-chronic-hepatic-failure-in-humans
#3
Jorge Guzman-Lepe, Eduardo Cervantes-Alvarez, Alexandra Collin de l'Hortet, Yang Wang, Wendy M Mars, Yoshinao Oda, Yuki Bekki, Masahiro Shimokawa, Huanlin Wang, Tomoharu Yoshizumi, Yoshihiko Maehara, Aaron Bell, Ira J Fox, Kazuki Takeishi, Alejandro Soto-Gutierrez
The mechanisms by which the liver fails in end-stage liver disease remain elusive. Disruption of the transcription factor network in hepatocytes has been suggested to mediate terminal liver failure in animals. However, this hypothesis remains unexplored in human subjects. To study the relevance of transcription factor expression in terminal stages of chronic liver failure in humans, we analyzed the expression of liver-enriched transcription factors (LETFs) hepatocyte nuclear factor (HNF)4α, HNF1α, forkhead box protein A2 (FOXA2), CCAAT/enhancer-binding protein (CEBP)α, and CEBPβ...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29761172/loss-of-hypoxia-inducible-factor-1%C3%AE-aggravates-%C3%AE-%C3%AE-t-cell-mediated-inflammation-during-acetaminophen-induced-liver-injury
#4
Tomohiro Suzuki, Shoko Minagawa, Takashi Yamazaki, Takatomo Arai, Mai Kanai, Satoko Shinjo, Nobuhito Goda
Acetaminophen (APAP)-induced liver injury is closely associated with acute hepatic inflammation. Hypoxia-inducible factor-1 (HIF-1) is activated during immunological processes and regulates gene expressions in various types of immune cells. Although HIF-1 controls the differentiation and functions of conventional T cells in chronic inflammation, the pathological importance of HIF-1 in innate-like T cells during acute inflammation remains unknown. Here, we investigated the role of HIF-1 in innate-like γδ T cells during APAP-induced acute liver injury...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29761171/coding-variants-in-pnpla3-and-tm6sf2-are-risk-factors-for-hepatic-steatosis-and-elevated-serum-alanine-aminotransferases-caused-by-a-glucagon-receptor-antagonist
#5
Cristina B Guzman, Suman Duvvuru, Anthony Akkari, Pallav Bhatnagar, Chakib Battioui, Wendra Foster, Xiaotian Michelle Zhang, Sudha S Shankar, Mark A Deeg, Naga Chalasani, Thomas A Hardy, Christof M Kazda, Sreekumar G Pillai
LY2409021 is a glucagon receptor antagonist that was associated with hepatic steatosis and elevated aminotransferases in phase 2 diabetes studies. We investigated the relationship between selected genetic variants and hepatic steatosis and elevated alanine aminotransferases (ALTs) associated with LY2409021. Patients participated in a 6-week placebo-controlled trial (I1R-MC-GLDI [GLDI], n = 246) and a 52-week placebo- and active comparator-controlled trial (I1R-MC-GLDJ [GLDJ], n = 158). GLDJ had endpoints at 6 months, including measures of hepatic fat fraction (HFF) by magnetic resonance imaging...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29761170/nicotinamide-adenine-dinucleotide-phosphate-reduced-oxidase-2-modulates-inflammatory-vigor-during-nonalcoholic-fatty-liver-disease-progression-in-mice
#6
Rajib Mukherjee, Maria E Moreno-Fernandez, Daniel A Giles, Monica Cappelletti, Traci E Stankiewicz, Calvin C Chan, Senad Divanovic
Nonalcoholic fatty liver disease (NAFLD) represents a disease spectrum ranging from benign steatosis to life-threatening cirrhosis and hepatocellular carcinoma. Elevated levels of reactive oxygen species (ROS) and exacerbated inflammatory responses have been implicated in NAFLD progression. Nicotinamide adenine dinucleotide phosphate (reduced) oxidase 2 (NOX2; also known as gp91Phox ), the main catalytic subunit of the nicotinamide adenine dinucleotide phosphate (reduced) oxidase complex, modulates ROS production, immune responsiveness, and pathogenesis of obesity-associated metabolic derangements...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29761169/prolonged-cenicriviroc-therapy-reduces-hepatic-fibrosis-despite-steatohepatitis-in-a-diet-induced-mouse-model-of-nonalcoholic-steatohepatitis
#7
Annie J Kruger, Bryan C Fuchs, Ricard Masia, Jacinta A Holmes, Shadi Salloum, Mozhdeh Sojoodi, Diego S Ferreira, Stephanie M Rutledge, Peter Caravan, Nadia Alatrakchi, Pam Vig, Eric Lefebvre, Raymond T Chung
Nonalcoholic steatohepatitis (NASH) is a progressive liver disease projected to become the leading cause of cirrhosis and liver transplantation in the next decade. Cenicriviroc (CVC), a dual chemokine receptor 2 and 5 antagonist, prevents macrophage trafficking and is under clinical investigation for the treatment of human NASH fibrosis. We assessed the efficacy and durability of short and prolonged CVC therapy in a diet-induced mouse model of NASH, the choline deficient, L-amino acid-defined, high-fat diet (CDAHFD) model...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29761168/outcomes-of-surgical-management-of-familial-intrahepatic-cholestasis-1-and-bile-salt-export-protein-deficiencies
#8
Laura N Bull, Ludmila Pawlikowska, Sandra Strautnieks, Irena Jankowska, Piotr Czubkowski, Jennifer L Dodge, Karan Emerick, Catherine Wanty, Sami Wali, Samra Blanchard, Florence Lacaille, Jane A Byrne, Albertien M van Eerde, Kaija-Leena Kolho, Roderick Houwen, Steven Lobritto, Vera Hupertz, Patricia McClean, Giorgina Mieli-Vergani, Etienne Sokal, Philip Rosenthal, Peter F Whitington, Joanna Pawlowska, Richard J Thompson
Progressive familial intrahepatic cholestasis (PFIC) with normal circulating gamma-glutamyl transpeptidase levels can result from mutations in the ATP8B1 gene (encoding familial intrahepatic cholestasis 1 [FIC1] deficiency) or the ABCB11 gene (bile salt export protein [BSEP] deficiency). We investigated the outcomes of partial external biliary diversion, ileal exclusion, and liver transplantation in these two conditions. We conducted a retrospective multicenter study of 42 patients with FIC1 deficiency (FIC1 patients) and 60 patients with BSEP deficiency (BSEP patients) who had undergone one or more surgical procedures (57 diversions, 6 exclusions, and 57 transplants)...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29761167/phenotypic-spectrum-and-diagnostic-pitfalls-of-abcb4-deficiency-depending-on-age-of-onset
#9
Stephanie Barbara Schatz, Christoph Jüngst, Verena Keitel-Anselmo, Ralf Kubitz, Christina Becker, Patrick Gerner, Eva-Doreen Pfister, Imeke Goldschmidt, Norman Junge, Daniel Wenning, Stephan Gehring, Stefan Arens, Dirk Bretschneider, Dirk Grothues, Guido Engelmann, Frank Lammert, Ulrich Baumann
Genetic variants in the adenosine triphosphate-binding cassette subfamily B member 4 ( ABCB4 ) gene, which encodes hepatocanalicular phosphatidylcholine floppase, can lead to different phenotypes, such as progressive familial intrahepatic cholestasis (PFIC) type 3, low phospholipid-associated cholelithiasis, and intrahepatic cholestasis of pregnancy. The aim of this multicenter project was to collect information on onset and progression of this entity in different age groups and to assess the relevance of this disease for the differential diagnosis of chronic liver disease...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29761166/ni-0801-an-anti-chemokine-c-x-c-motif-ligand-10-antibody-in-patients-with-primary-biliary-cholangitis-and-an-incomplete-response-to-ursodeoxycholic-acid
#10
Kathy L de Graaf, Geneviève Lapeyre, Florence Guilhot, Walter Ferlin, Stuart M Curbishley, Marco Carbone, Paul Richardson, Sulleman Moreea, C Anne McCune, Stephen D Ryder, Roger W Chapman, Annarosa Floreani, David E Jones, Cristina de Min, David H Adams, Pietro Invernizzi
NI-0801 is a fully human monoclonal antibody against chemokine (C-X-C motif) ligand 10 (CXCL10), which is involved in the recruitment of inflammatory T cells into the liver. The safety and efficacy of NI-0801 was assessed in patients with primary biliary cholangitis. In this open-label phase 2a study, patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid received six consecutive intravenous administrations of NI-0801 (10 mg/kg) every 2 weeks. Patients were followed up for 3 months after the last infusion...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29761165/a-real-world-observational-cohort-of-patients-with-primary-biliary-cholangitis-target-primary-biliary-cholangitis-study-design-and-rationale
#11
Cynthia Levy, Christopher L Bowlus, Elizabeth Carey, Julie M Crawford, Karen Deane, Marlyn J Mayo, W Ray Kim, Michael W Fried
Primary biliary cholangitis (PBC) is a rare chronic cholestatic liver disease that may progress to biliary cirrhosis if left untreated. The first-line therapy for PBC is ursodeoxycholic acid (UDCA). Unfortunately, 1 of 3 patients does not respond to UDCA. These patients are at risk for developing clinical events, including cirrhosis, complications of portal hypertension, hepatocellular carcinoma, liver transplant, or death. Recently, the U.S. Food and Drug Administration approved obeticholic acid to be used in certain patients with PBC...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29761164/periostin-and-mesothelin-potential-predictors-of-malignant-progression-in-intrahepatic-cholangiocarcinoma
#12
EDITORIAL
Pranoti Mandrekar, Vincenzo Cardinale
No abstract text is available yet for this article.
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29619424/liver-stiffness-measurement-predicted-liver-related-events-and-all-cause-mortality-a-systematic-review-and-nonlinear-dose-response-meta-analysis
#13
Junna Wang, Jiajun Li, Quan Zhou, Dandan Zhang, Qiu Bi, Yulin Wu, Wenxiang Huang
Numerous studies have investigated the prognosis value of the liver stiffness measurement (LSM) by transient elastography in assessing the risk of liver-related events (LREs) and all-cause mortality in patients with chronic liver disease (CLD). However, the shape of the dose-response relationship between them remains unclear. We searched PubMed, Embase, the Cochrane Library, and reference lists of articles for studies published up to July 1, 2017, that assessed the LSM in predicting LREs and all-cause mortality among subjects with CLD...
April 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29619423/a-single-blood-test-adjusted-for-different-liver-fibrosis-targets-improves-fibrosis-staging-and-especially-cirrhosis-diagnosis
#14
Paul Calès, Jérôme Boursier, Frédéric Oberti, Valérie Moal, Isabelle Fouchard Hubert, Sandrine Bertrais, Gilles Hunault, Marie Christine Rousselet
Fibrosis blood tests are usually developed using significant fibrosis, which is a unique diagnostic target; however, these tests are employed for other diagnostic targets, such as cirrhosis. We aimed to improve fibrosis staging accuracy by simultaneously targeting biomarkers for several diagnostic targets. A total of 3,809 patients were included, comprising 1,012 individuals with chronic hepatitis C (CHC) into a derivation population and 2,797 individuals into validation populations of different etiologies (CHC, chronic hepatitis B, human immunodeficiency virus/CHC, nonalcoholic fatty liver disease, alcohol) using Metavir fibrosis stages as reference...
April 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29619422/the-molecular-adsorbent-recirculating-system-in-posthepatectomy-liver-failure-results-from-a-prospective-phase-i-study
#15
Stefan Gilg, Ernesto Sparrelid, Lars Saraste, Greg Nowak, Staffan Wahlin, Cecilia Strömberg, Lars Lundell, Bengt Isaksson
Posthepatectomy liver failure (PHLF) represents the single most important cause of postoperative mortality after major liver resection, yet no effective treatment option is available. Extracorporeal liver support devices might be helpful, but systematic studies are lacking. Accordingly, we aimed to assess the safety and feasibility of the Molecular Adsorbent Recirculating System (MARS) in patients with PHLF. Between December 2012 and May 2015, a total of 206 patients underwent major or extended hepatectomy, and 10 consecutive patients with PHLF (according to the Balzan 50:50 criteria) were enrolled into the study...
April 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29619421/influence-of-spontaneous-splenorenal-shunts-on-clinical-outcomes-in-decompensated-cirrhosis-and-after-liver-transplantation
#16
Karen Saks, Kyle K Jensen, Joel McLouth, Justine Hum, Joseph Ahn, Atif Zaman, Michael F Chang, Alice Fung, Barry Schlansky
Cirrhosis and portal hypertension can lead to the formation of a spontaneous splenorenal shunt (SSRS) that may divert portal blood flow to the systemic circulation and reduce hepatic perfusion. Our aims were to evaluate SSRSs as an independent prognostic marker for mortality in patients with decompensated cirrhosis and the influence of SSRSs on liver transplantation (LT) outcomes. We retrospectively analyzed adult patients with decompensated cirrhosis undergoing LT evaluation from January 2001 to February 2016 at a large U...
April 2018: Hepatology communications
https://www.readbyqxmd.com/read/29619420/changes-in-natural-killer-cells-and-exhausted-memory-regulatory-t-cells-with-corticosteroid-therapy-in-acute-autoimmune-hepatitis
#17
Hannah C Jeffery, Manjit K Braitch, Chris Bagnall, James Hodson, Louisa E Jeffery, Rebecca E Wawman, Lin Lee Wong, Jane Birtwistle, Helen Bartlett, Ansgar W Lohse, Gideon M Hirschfield, Jessica Dyson, David Jones, Stefan G Hubscher, Paul Klenerman, David H Adams, Ye H Oo
Autoimmune hepatitis (AIH) is an immune-mediated liver disease currently treated by immunosuppressive medications with significant side effects. Thus, novel mechanistic treatments are greatly needed. We performed prospective deep immunophenotyping of blood immune cells in patients with acute AIH before and after corticosteroid therapy. Blood samples from 26 patients with acute AIH (United Kingdom-AIH Consortium) were phenotyped by flow cytometry at baseline and 4 months after starting corticosteroids. Pretreatment liver tissues were stained for forkhead box P3-positive (FOXP3POS ) regulatory T cells (Tregs), clusters of differentiation (CD)56POS natural killer (NK) cells, and chemokine (C-X-C motif) ligand 10...
April 2018: Hepatology communications
https://www.readbyqxmd.com/read/29619419/tumor-necrosis-factor-%C3%AE-mediated-hepatocyte-apoptosis-stimulates-fibrosis-in-the-steatotic-liver-in-mice
#18
Yosuke Osawa, Ekumi Kojika, Yukiko Hayashi, Masamichi Kimura, Koji Nishikawa, Sachiyo Yoshio, Hiroyoshi Doi, Tatsuya Kanto, Kiminori Kimura
Hepatocyte apoptosis has been implicated in the progression of nonalcoholic steatohepatitis. However, it is unclear whether the induction of tumor necrosis factor (TNF)-α-mediated hepatocyte apoptosis in the simple fatty liver triggers liver fibrosis. To address this question, high-fat diet-fed mice were repeatedly administered D-galactosamine, which increases the sensitivity of hepatocytes to TNF-α-mediated apoptosis. In mice treated with a high-fat diet plus D-galactosamine, hepatocyte apoptosis and liver fibrosis were induced, whereas both apoptosis and fibrosis were inhibited in these mice following gut sterilization with antimicrobials or knockout of TNF-α...
April 2018: Hepatology communications
https://www.readbyqxmd.com/read/29619418/the-role-of-intestinal-c-type-regenerating-islet-derived-3-lectins-for-nonalcoholic-steatohepatitis
#19
Sena Bluemel, Lirui Wang, Cameron Martino, Suhan Lee, Yanhan Wang, Brandon Williams, Angela Horvath, Vanessa Stadlbauer, Karsten Zengler, Bernd Schnabl
C-type regenerating islet derived-3 (Reg3) lectins defend against pathogens and keep commensal bacteria at a distance. Deficiency of Reg3g and Reg3b facilitates alcohol-induced bacterial translocation and alcoholic liver disease. Intestinal Reg3g is down-regulated in animal models of diet-induced obesity, but the functional consequences for nonalcoholic steatohepatitis (NASH) are unknown. The aim of this study was to investigate the role of Reg3 lectins in NASH. NASH was induced by a Western-style fast-food diet in mice deficient for Reg3g or Reg3b and in transgenic mice overexpressing Reg3g in intestinal epithelial cells ( Reg3g Tg)...
April 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29619417/nonalcoholic-fatty-liver-disease-contributes-to-subclinical-atherosclerosis-a-systematic-review-and-meta-analysis
#20
Yao-Yao Zhou, Xiao-Dong Zhou, Sheng-Jie Wu, Dan-Hong Fan, Sven Van Poucke, Yong-Ping Chen, Shen-Wen Fu, Ming-Hua Zheng
Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease. In our meta-analysis, we aimed to assess the correlation of NAFLD and four surrogate markers of subclinical atherosclerosis. PubMed, Embase, and the Cochrane Library were searched up until April 2017. Original studies investigating the association between NAFLD and subclinical atherosclerosis were included. The outcome data were extracted and pooled for the effect estimate by using a random-effects model...
April 2018: Hepatology Communications
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