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Hepatology: Official Journal of the American Association for the Study of Liver Diseases

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https://www.readbyqxmd.com/read/28926121/new-pediatric-percentiles-of-liver-enzyme-serum-levels-alt-ast-ggt-effects-of-age-sex-bmi-and-pubertal-stage
#1
Sarah Bussler, Mandy Vogel, Diana Pietzner, Kristian Harms, Theresa Buzek, Melanie Penke, Norman Händel, Antje Körner, Ulrich Baumann, Wieland Kiess, Gunter Flemming
The present study aims to clarify the effects of sex, age, BMI and puberty on transaminase serum levels in children and adolescents and to provide new age- and sex-related percentiles for alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (GGT). Venous blood and anthropometric data were collected from 4,126 cases. Excluded were cases of participants with potential hepatotoxic medication, with evidence of potential illness at the time of blood sampling and non-normal BMI (BMI < 10(th) or > 90(th) )...
September 19, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28926120/glecaprevir-pibrentasvir-for-hcv-genotype-3-patients-with-cirrhosis-and-or-prior-treatment-experience-a-partially-randomized-phase-iii-clinical-trial
#2
David Wyles, Fred Poordad, Stanley Wang, Laurent Alric, Franco Felizarta, Paul Y Kwo, Benedict Maliakkal, Kosh Agarwal, Tarek Hassanein, Frank Weilert, Samuel S Lee, Jens Kort, Sandra S Lovell, Ran Liu, Chih-Wei Lin, Tami Pilot-Matias, Preethi Krishnan, Federico J Mensa
BACKGROUND: This study assessed the efficacy and safety of ribavirin (RBV)-free coformulated glecaprevir/pibrentasvir (G/P) in patients with hepatitis C virus (HCV) genotype (GT) 3 infection with either prior treatment experience and/or compensated cirrhosis, a patient population with limited treatment options. METHODS: SURVEYOR-II, Part 3 was a partially-randomized, open-label, multicenter, phase 3 study. Treatment-experienced (prior interferon (IFN) or pegIFN ± ribavirin or SOF plus ribavirin ± pegIFN therapy) patients without cirrhosis were randomized 1:1 to receive 12 or 16 weeks of G/P (300 mg/120 mg) once daily...
September 19, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28926118/chop-induced-loss-of-intestinal-epithelial-stemness-contributes-to-bile-duct-ligation-induced-cholestatic-liver-injury
#3
Runping Liu, Xiaojiaoyang Li, Zhiming Huang, Derrick Zhao, Bhagyalaxmi Sukka Ganesh, Guanhua Lai, William M Pandak, Phillip B Hylemon, Jasmohan S Bajaj, Arun J Sanyal, Huiping Zhou
Impaired intestinal barrier function promotes the progression of various liver diseases including cholestatic liver disease. The close association of primary sclerosing cholangitis (PSC) with inflammatory bowel disease highlights the importance of the gut-liver axis. It has been reported that bile duct ligation (BDL)-induced liver fibrosis is significantly reduced in C/EBP homologous protein knock out (CHOP(-/-) ) mice. However, the underlying mechanisms remain unclear. In the current study, we demonstrate that BDL induces striking and acute hepatic ER stress responses after 1 day, which return to normal after 3 days...
September 19, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28926117/bile-acids-in-nash-pathophysiological-driving-force-or-innocent-bystanders
#4
EDITORIAL
Daniel Jahn, Andreas Geier
No abstract text is available yet for this article.
September 19, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28922472/mirna-506-promotes-primary-biliary-cholangitis-like-features-in-cholangiocytes-and-immune-activation
#5
Oihane Erice, Patricia Munoz-Garrido, Javier Vaquero, Maria J Perugorria, Maite G Fernandez-Barrena, Elena Saez, Alvaro Santos-Laso, Ander Arbelaiz, Raul Jimenez-Agüero, Joaquin Fernandez-Irigoyen, Enrique Santamaria, Verónica Torrano, Arkaitz Carracedo, Meenakshisundaram Ananthanarayanan, Marco Marzioni, Jesus Prieto, Ulrich Beuers, Ronald P Oude Elferink, Nicholas F LaRusso, Luis Bujanda, Jose J G Marin, Jesus M Banales
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease associated with autoimmune phenomena targeting intrahepatic bile duct cells (cholangiocytes). Although PBC etiopathogenesis still remains obscure, development of anti-mitochondrial auto-antibodies against pyruvate dehydrogenase complex-E2 (PDC-E2) is a common feature. MicroRNA (miR) dysregulation occurs in liver and immune cells of PBC patients, but their functional relevance is largely unknown. We previously reported that miR-506 is overexpressed in PBC cholangiocytes and directly targets both Cl(-) /HCO3(-) anion exchanger 2 (AE2) and type III inositol 1,4,5-trisphosphate receptor (InsP3R3), leading to cholestasis...
September 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28922468/reply-to-hep-17-1544
#6
LETTER
Barret Rush, Keith R Walley, Leo Anthony Celi, Neil Rajoriya, Mayur Brahmania
No abstract text is available yet for this article.
September 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28921652/necessity-of-more-sensitivity-analyses-and-interpretations-from-public-health-perspectives
#7
LETTER
Vasveebye Sonoo, Jay V Kumar, Xibei Liu, Johnson Ukken, Mary Froehlich, Ji Won Yoo
No abstract text is available yet for this article.
September 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28921638/graft-infiltrating-pd-l1-hi-cross-dressed-dendritic-cells-regulate-anti-donor-t-cell-responses-in-mouse-liver-transplant-tolerance
#8
Yoshihiro Ono, Angelica Perez-Gutierrez, Toshimasa Nakao, Helong Dai, Geoffrey Camirand, Osamu Yoshida, Shinichiro Yokota, Donna Beer Stolz, Mark A Ross, Adrian E Morelli, David A Geller, Angus W Thomson
While a key role of cross-dressing has been established in immunity to viral infection and more recently in the instigation of transplant rejection, its role in tolerance is unclear. Here, we investigated the role of intra-graft dendritic cells (DC) and cross-dressing in mouse major histocompatibility complex (MHC)-mismatched liver transplant tolerance that occurs without therapeutic immunosuppression. While donor interstitial DC diminished rapidly following transplantation, they were replaced in the liver by host DC that peaked on postoperative day (POD) 7 and persisted indefinitely...
September 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28921625/solving-doubts-about-l-ornithine-l-aspartate-for-overt-he-whom-and-how-to-treat
#9
EDITORIAL
Piero Amodio, Javier Ampuero
Randomized controlled trials about the treatment of bouts of overt hepatic encephalopathy (OHE) are difficult to design and interpret, since bouts of OHE i) are relatively short episodes in which the dynamic of the response to treatment is relevant, ii) their occurrence and treatment is frequently linked to precipitating events. The study by Sidhu et al. in this issue of Hepatology is a model of proper design and provides evidence that L-ornithine-L-aspartate infusion for 5 days is an effective add on treatment to speed up recovery from bouts of OHE in comparison with a placebo treatment that does not contain amino acid nutrients...
September 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28921620/late-hepatitis-b-reactivation-following-daa-based-treatment-of-recurrent-hepatitis-c-in-an-anti-hbc-positive-liver-transplant-recipient
#10
Julien Vionnet, Manuel Pascual, Barbara Testoni, Christophe Combet, Sébastien Godat, Sandrine Vijgen, Vincent Aubert, Laura Rubbia-Brandt, Fabien Zoulim, Darius Moradpour
No abstract text is available yet for this article.
September 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28921602/human-leukocyte-antigen-variants-and-risk-of-hepatocellular-carcinoma-modified-by-hcv-genotypes-a-genome-wide-association-study
#11
Mei-Hsuan Lee, Yu-Han Huang, Hsuan-Yu Chen, Charles Seik-Soon Khor, Ya-Hsuan Chang, Yu-Ju Lin, Chin-Lan Jen, Sheng-Nan Lu, Hwai-I Yang, Nao Nishida, Masaya Sugiyama, Masashi Mizokami, Yong Yuan, Gibert L'Italien, Katsushi Tokunaga, Chien-Jen Chen
BACKGROUND & AIMS: We conducted a genome-wide association study (GWAS) to discover genetic variants associated with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). METHODS: We genotyped 502 HCC cases and 749 non-HCC controls by using the Axiom(TM) -CHB genome-wide array. After identifying single nucleotide polymorphism (SNP) cluster located in the human leukocyte antigen region which were potentially associated with HCC, HLA-DQB1 genotyping was performed to analyze 994 anti-HCV seropositives collected in the period of 1991-2013 in a community-based cohort for evaluating long-term predictability of HLA variants for identifying the risk of HCC...
September 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28921595/the-interplay-of-type-i-and-type-ii-interferons-in-murine-autoimmune-cholangitis-as-a-basis-for-sex-biased-autoimmunity
#12
Heekyong R Bae, Deborah L Hodge, Guo-Xiang Yang, Patrick S C Leung, Sathi Babu Chodisetti, Julio C Valencia, Michael Sanford, John M Fenimore, Ziaur S M Rahman, Koichi Tsuneyama, Gary L Norman, M Eric Gershwin, Howard A Young
We have reported a murine model of autoimmune cholangitis, generated by altering the AU rich element by deletion of the IFN-γ 3'UTR region (coined ARE-Del(-/-) ), that has striking similarities to human primary biliary cholangitis (PBC) with female predominance. Previously, we suggested that the gender bias of autoimmune cholangitis was secondary to intense and sustained type I and II IFN signaling. Based on this thesis, and to define the mechanisms that lead to portal inflammation, we specifically addressed the hypothesis that type I IFNs are the driver of this disease...
September 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28921593/in-reply-to-xue-et-al-developing-a-prediction-model-for-cardiovascular-risk-after-orthotopic-liver-transplantation
#13
LETTER
Lisa B VanWagner, Hongyan Ning, Maureen Whitsett, Josh Levitsky, Sarah Uttal, John T Wilkins, Michael M Abecassis, Daniela P Ladner, Anton I Skaro, Donald M Lloyd-Jones
No abstract text is available yet for this article.
September 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28921592/radiosensitization-by-inhibiting-dna-repair-turning-the-spotlight-on-homologous-recombination
#14
EDITORIAL
Bhanu P Venkatesulu, Sunil Krishnan
No abstract text is available yet for this article.
September 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28921590/developing-a-prediction-model-for-cardiovascular-risk-after-orthotopic-liver-transplantation
#15
LETTER
Fu-Shan Xue, Ya-Yang Liu, Gui-Zhen Yang
No abstract text is available yet for this article.
September 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28913935/induction-of-cancer-cell-stemness-by-depletion-of-macrohistone-h2a1-in-hepatocellular-carcinoma
#16
Oriana Lo Re, Caterina Fusilli, Francesca Rappa, Matthias Van Haele, Julien Douet, Jana Pindjakova, Sura Wanessa Rocha, Illar Pata, Barbora Valčíková, Stjepan Uldrijan, Raymond S Yeung, Christina Alves Peixoto, Tania Roskams, Marcus Buschbeck, Tommaso Mazza, Manlio Vinciguerra
Hepatocellular carcinomas (HCC) contain a sub-population of cancer stem cells (CSCs), which exhibit stem-cell like features and are responsible for tumor relapse, metastasis, and chemoresistance. The development of effective treatments for HCC will depend on a molecular-level understanding of the specific pathways driving CSC emergence and stemness. MacroH2A1 is a variant of the histone H2A and an epigenetic regulator of stem cell function, where it promotes differentiation and, conversely, acts as a barrier to somatic cell reprogramming...
September 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28902431/cardiovascular-predictors-of-death-in-patients-with-cirrhosis
#17
Maurizio Cesari, Anna Chiara Frigo, Marta Tonon, Paolo Angeli
Cirrhotic cardiomyopathy is associated with poor outcomes in patients with cirrhosis. We investigated if subclinical cardiac morphologic and functional modifications can influence survival in cirrhotic patients during follow-up. A series of cirrhotic patients without cardiovascular or pulmonary disease underwent standard and tissue Doppler echocardiography to assess left ventricular (LV) geometry, systo/diastolic function and the main haemodynamic parameters. After baseline evaluation 115 cirrhotic patients were followed up for at least 6 years...
September 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28902428/nuclear-lamina-genetic-variants-including-a-truncated-lap2-in-twins-and-siblings-with-nonalcoholic-fatty-liver-disease
#18
Graham F Brady, Raymond Kwan, Peter J Ulintz, Phirum Nguyen, Shirin Bassirian, Venkatesha Basrur, Alexey I Nesvizhskii, Rohit Loomba, M Bishr Omary
Nonalcoholic fatty liver disease (NAFLD) is becoming the major chronic liver disease in many countries. Its pathogenesis is multifactorial but twin and familial studies indicate significant heritability, which is not fully explained by currently-known genetic susceptibility loci. Notably, mutations in genes encoding nuclear lamina proteins, including lamins, cause lipodystrophy syndromes that include NAFLD. We hypothesized that variants in lamina-associated proteins predispose to NAFLD and used a candidate gene-sequencing approach to test for variants in 10 nuclear lamina-related genes in a cohort of 37 twin and sibling pairs: 21 individuals with, and 53 without, NAFLD...
September 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28902427/nlrp3-inflammasome-driven-liver-injury-and-fibrosis-roles-of-il-17-and-tnf
#19
Alexander Wree, Matthew D McGeough, Maria Eugenia Inzaugarat, Akiko Eguchi, Susanne Schuster, Casey D Johnson, Carla A Peña, Lukas J Geisler, Bettina G Papouchado, Hal M Hoffman, Ariel E Feldstein
The NLRP3 inflammasome, a caspase-1 activation platform plays a key role in the modulation of liver inflammation and fibrosis. Here, we tested the hypothesis that interleukin 17 (IL-17) and tumor necrosis factor (TNF) are key cytokines involved in amplifying and perpetuating the liver damage and fibrosis resulting from NLRP3 activation. To address this hypothesis gain of function Nlrp3(A350V) knock-in mice were bred onto il17a and Tnf knockout backgrounds allowing for constitutive Nlrp3 activation in myeloid derived cells in mice deficient in IL-17 or TNF...
September 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28902419/reassessing-the-safety-concerns-of-utilizing-blood-donations-from-patients-with-hemochromatosis
#20
REVIEW
Adam C Winters, Douglas Tremblay, Suzanne Arinsburg, John Mascarenhas, Thomas D Schiano
Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism which may lead to iron overload. Clinical penetrance is low, however those afflicted may develop cirrhosis, hepatocellular carcinoma, diabetes mellitus and cardiomyopathy. Treatment involves regular phlebotomy to reduce the systemic iron burden. In many countries-including the United States-numerous blood centers do not accept donated blood obtained from HH patients during therapeutic phlebotomy and there are inconsistent positions regarding this globally...
September 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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