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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/30415504/hsd17b13-is-a-hepatic-retinol-dehydrogenase-associated-with-histological-features-of-non-alcoholic-fatty-liver-disease
#1
Yanling Ma, Olga V Belyaeva, Philip M Brown, Koji Fujita, Katherine Valles, Suman Karki, Ynto S de Boer, Christopher Koh, Yanhua Chen, Xiaomeng Du, Samuel K Handelman, Vincent Chen, Elizabeth K Speliotes, Cara Nestlerode, Emmanuel Thomas, David E Kleiner, Joseph M Zmuda, Arun J Sanyal, Natalia Y Kedishvili, T Jake Liang, Yaron Rotman
Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. A single nucleotide polymorphism (SNPs), rs6834314, was associated with serum liver enzymes in the general population, presumably reflecting liver fat or injury. We studied rs6834314 and its nearest gene, HSD17B13 (17-beta hydroxysteroid dehydrogenase 13) to identify associations with histological features of NAFLD, and to characterize the functional role of HSD17B13 in NAFLD pathogenesis. The minor allele of rs6834314 was significantly associated with increased steatosis, but decreased inflammation, ballooning, Mallory-Denk bodies, and liver enzyme levels in 768 adult Caucasians with biopsy-proven NAFLD, and with cirrhosis in the general population...
November 11, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30414342/intestinal-immune-dysregulation-driven-by-dysbiosis-promotes-barrier-disruption-and-bacterial-translocation-in-rats-with-cirrhosis
#2
Leticia Muñoz, María-José Borrero, María Úbeda, Elisa Conde, Rosa Del Campo, Macarena Rodríguez-Serrano, Margaret Lario, Ana-María Sánchez-Díaz, Oscar Pastor, David Díaz, Laura García-Bermejo, Jorge Monserrat, Melchor Álvarez-Mon, Agustín Albillos
In cirrhosis, intestinal dysbiosis, intestinal barrier impairment and systemic immune system abnormalities lead to gut bacterial translocation (GBT) and bacterial infection. However, intestinal immune system dysfunction and its contribution to barrier damage are poorly understood. This study correlates immune system dysregulation in the intestines of rats at different stages of CCl4 -induced cirrhosis with barrier function and pathogenic microbiota. The following variables were addressed in the small intestine: intraepithelial and lamina propria lymphocyte (IEL, LPL) activation status and cytokine production (flow cytometry), cytokine mRNA and protein expression (real-time quantitative PCR (qPCR) and immunofluorescence), microbiota composition of ileum content (16SrDNA massive sequencing), permeability (fecal albumin loss) and epithelial junctions (immunohistochemistry and immunofluorescence)...
November 10, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30411380/the-epidermal-growth-factor-receptor-ligand-amphiregulin-protects-from-cholestatic-liver-injury-and-regulates-bile-acids-synthesis
#3
Eva Santamaría, Carlos M Rodríguez-Ortigosa, Iker Uriarte, Maria U Latasa, Raquel Urtasun, Gloria Alvarez-Sola, Marina Bárcena-Varela, Leticia Colyn, Sara Arcelus, Maddalen Jiménez, Kathleen Deutschmann, Ana Peleteiro-Vigil, Julian Gómez-Cambronero, Malgorzata Milkiewicz, Piotr Milkiewicz, Bruno Sangro, Verena Keitel, Maria J Monte, Jose Jg Marin, Maite G Fernández-Barrena, Matias A Ávila, Carmen Berasain
Intrahepatic accumulation of bile acids (BA) causes hepatocellular injury. Upon liver damage, a potent protective response is mounted to restore the organ's function. Epidermal growth factor receptor (EGFR) signaling is essential for regeneration after most types of liver damage, including cholestatic injury. However, EGFR can be activated by a family of growth factors induced during liver injury and regeneration. We evaluated the role of the EGFR ligand amphiregulin (AREG) during cholestatic liver injury and the regulation of AREG expression by BA...
November 8, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30411378/human-cd96-correlates-to-nk-cell-exhaustion-and-predicts-the-prognosis-of-human-hepatocellular-carcinoma
#4
Haoyu Sun, Qiang Huang, Mei Huang, Hao Wen, Renyong Lin, Meijuan Zheng, Kun Qu, Kun Li, Haiming Wei, Weihua Xiao, Rui Sun, Zhigang Tian, Cheng Sun
Immune checkpoint blockade has become a promising therapeutic approach to reverse immune cell exhaustion. Co-inhibitory CD96 and TIGIT, together with co-stimulatory CD226, bind to common ligand CD155. The balancing between three receptors fine tunes the immune responses against tumors. In this study, we investigated the expression of CD96, TIGIT and CD226 in 55 fresh human hepatocellular carcinoma (HCC) samples, 236 paraffin-embedded HCC samples, and 20 normal human livers. The cumulative percentage, absolute count, and MFI of CD96+ NK cells are significantly increased in the intratumoral tissues of HCC, and break the balance between three receptors...
November 8, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30398671/estimating-prevalence-of-hepatitis-c-virus-infection-in-the-united-states-2013-2016
#5
Megan G Hofmeister, Elizabeth M Rosenthal, Laurie K Barker, Eli S Rosenberg, Meredith A Barranco, Eric W Hall, Brian R Edlin, Jonathan Mermin, John W Ward, A Blythe Ryerson
Hepatitis C virus (HCV) infection is the most commonly reported bloodborne infection in the United States, causing substantial morbidity and mortality and costing billions of dollars annually. To update the estimated HCV prevalence among all adults aged ≥18 years in the United States, we analyzed 2013-2016 data from the National Health and Nutrition Examination Survey (NHANES) to estimate the prevalence of HCV in the noninstitutionalized civilian population and used a combination of literature reviews and population size estimation approaches to estimate the HCV prevalence and population sizes for four additional populations: incarcerated people, unsheltered homeless people, active-duty military personnel, and nursing home residents...
November 6, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30394550/a-novel-regulatory-role-of-apoptosis-antagonizing-transcription-factor-in-the-pathogenesis-of-nafld-and-hcc
#6
Divya P Kumar, Prasanna K Santhekadur, Mulugeta Seneshaw, Faridoddin Mirshahi, Cora Uram Tuculescu, Arun J Sanyal
Hepatocellular carcinoma (HCC) is increasing as a cause of liver-related mortality largely due to the growing burden of nonalcoholic steatohepatitis (NASH). The mechanisms of HCC development in nonalcoholic fatty liver disease (NAFLD) are incompletely understood. We initially identified apoptosis antagonizing transcription factor (AATF) to be associated with HCC in a mouse model of NASH that develops HCC without the addition of specific carcinogens. AATF also called che-1, is a transcriptional factor that is highly conserved among eukaryotes...
November 5, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30394549/immunosuppression-minimization-trials-in-liver-transplantation-can-we-predict-humoral-response-to-asses-eligibility
#7
LETTER
Magdalena Meszaros, Jose Ursic-Bedoya, Stéphanie Faure, Georges-Philippe Pageaux
We have read with great interest the article by Jucaud et al. (1) reporting that de novo donor-specific HLA antibodies (dnDSA) development during immunosuppression (IS) withdrawal in liver transplantation (LT) was associated with acute rejection and prevented further attempts of IS withdrawal. This article is protected by copyright. All rights reserved.
November 5, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30393873/confirmation-of-the-optimization-to-prevent-the-first-oesophageal-variceal-bleeding
#8
LETTER
Xinwen Yan, Ziyuan Zou, Xiaolong Qi
We read with great interest the network meta-analysis by Shama et al. (1) The authors compared different therapies for the first prophylaxis of esophageal variceal bleeding, based on the direct and indirect evidence and concluded that non-selective β-blockers (NSBBs) could be the optimization. We commend the authors for undertaking such a rigorous network meta-analysis and would like to share our opinion on the details in methods. This article is protected by copyright. All rights reserved.
November 4, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30387174/new-highly-diverse-hepatitis-c-strains-detected-in-sub-saharan-africa-have-unknown-susceptibility-to-direct-acting-antiviral-treatments
#9
Chris Davis, George S Mgomella, Ana da Silva Filipe, Eric H Frost, Genevieve Giroux, Joseph Hughes, Catherine Hogan, Pontiano Kaleebu, Gershim Asiki, John McLauchlan, Marc Niebel, Ponsiano Ocama, Cristina Pomila, Oliver G Pybus, Jacques Pépin, Peter Simmonds, Josh B Singer, Vattipally B Sreenu, Clara Wekesa, Elizabeth H Young, Donald G Murphy, Manj Sandhu, Emma C Thomson
BACKGROUND AND RATIONALE FOR THE STUDY: The global plan to eradicate hepatitis C (HCV) led by the World Health Organisation (WHO) outlines the use of highly effective direct-acting antiviral drugs (DAAs) to achieve elimination by 2030. Identifying individuals with active disease and investigation of the breadth of diversity of the virus sub-Saharan Africa (SSA) is essential as genotypes in this region (where very few clinical trials have been carried out) are distinct from those found in other parts of the world...
November 2, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30383299/using-proper-methods-to-identify-cirrhosis-patients-in-administrative-databases-is-crucial-to-correctly-predict-outcomes
#10
LETTER
Abdel Aziz Shaheen, Mark G Swain
We would like to congratulate Mumtaz et al.1 for their important study attempting to develop and validate a risk score to predict 30-day hospital readmission in decompensated cirrhosis patients using the US nationwide readmission database (NRD). The identification of cirrhosis patients at high-risk for readmission is critical for developing processes to effectively address this problem. However, flaws in patient identification challenge the utility of the risk-score outlined in this study. This article is protected by copyright...
November 1, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30382597/cellular-plasticity-in-liver-regeneration-spotlight-on-cholangiocytes
#11
Janina E E Tirnitz-Parker, Stuart J Forbes, John K Olynyk, Grant A Ramm
The liver's remarkable capacity to self-repair and regenerate following tissue injury has been recognised since the ancient Greek myth of Prometheus. However the diverse potential sources of this regenerative capacity have been an area of hot debate and only recently have studies started to unravel the actual degree of hepatic cell plasticity. The article by Deng X, Zhang X, Li W et al. Chronic liver injury induces conversion of biliary epithelial cells into hepatocytes. Cell Stem Cell 2018; 23:114-122 established through lineage tracing experiments using a double-fluorescent reporter system that biliary epithelial cells significantly contributed to hepatocyte regeneration in two murine chronic liver injury models...
November 1, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30382593/surgical-resection-vs-transarterial-chemoembolization-for-intermediate-stage-hepatocellular-carcinoma-bclc-b-an-unsolved-question
#12
LETTER
Ismail Labgaa, Nicolas Demartines, Emmanuel Melloul
We have read the article of Hyun MH et al. with great interest (1). We commend the authors for this study that tackles a crucial point in the treatment of hepatocellular carcinoma (HCC). There is a critical need to refine and eventually to expand the selection criteria of HCC patients who may benefit from curative therapies such as surgical resection (SR). There is accumulating evidence on improved survival after SR as opposed to transarterial chemoembolization (TACE) in patients with intermediate stage HCC (Barcelona Clinic Liver Cancer Stage B (BCLC-B)), although American (AASLD) and European (EASL) consensus guidelines recommend TACE in this setting (2, 3)...
November 1, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30382584/frailty-psychoactive-medications-and-cognitive-dysfunction-are-associated-with-poor-patient-reported-outcomes-in-cirrhosis
#13
Elliot B Tapper, Jad Baki, Neehar D Parikh, Anna S Lok
Cirrhosis is associated with disabling symptoms and diminished health-related quality of life (HRQOL). However, for patients with compensated disease, data are limited regarding associations with poor patient-reported outcomes (PROs). We prospectively enrolled 300 patients with cirrhosis and portal hypertension without a history of hepatic encephalopathy and reviewed medical and pharmacy records. We characterized determinants of PROs using the SF-8 scale (0-100) and sleep quality using the Pittsburgh Sleep Quality Index (poor sleep >5)...
November 1, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30382583/smoking-and-hepatitis-b-virus-related-hepatocellular-carcinoma-risk-the-mediating-roles-of-viral-load-and-alanine-aminotransferase
#14
Ya-Hui Wang, Ya-Hui Chuang, Chih-Feng Wu, Meng-Chin Jan, Wan-Jung Wu, Chih-Lin Lin, Chun-Jen Liu, Ya-Chien Yang, Pei-Jer Chen, Shi-Ming Lin, Mong-Hsun Tsai, Yi-Wen Huang, Ming-Whei Yu
Smoking interacts with hepatitis B virus (HBV) to increase risk of hepatocellular carcinoma (HCC) that might be explained by its role in antiviral immunity. We aimed to evaluate the potential mediating role of viral load and/or alanine aminotransferase (ALT) in the relation of smoking with HBV-associated HCC risk. Using multiple mediation analyses to analyze data from 209 HCC cases and 1256 controls nested within a cohort of 4841 male HBV carriers, we found that the effect of smoking on the risk of subsequent HCC was substantially mediated through viral load (percent mediated= 31...
November 1, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30382576/challenges-and-opportunities-in-the-clinical-development-of-immune-checkpoint-inhibitors-for-hepatocellular-carcinoma
#15
REVIEW
Michael J Flynn, Anwar A Sayed, Rohini Sharma, Abdul Siddique, David J Pinato
After a decade of stagnation in drug development, therapeutic reversal of immune-exhaustion with immune checkpoint inhibitors (ICPI) has been shown to be effective in advanced hepatocellular carcinoma (HCC). The clinical development of novel ICPIs continues at a rapid pace, with more than 50 clinical trials of immunotherapeutic agents registered as of May 2018 for this indication. The development of ICPI is particularly challenging in patients with HCC, a population with unique features which impact on safety and efficacy of immune-modulating therapies...
November 1, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30376183/the-critical-issue-of-restaging-patients-with-hepatocellular-carcinoma
#16
LETTER
Alessandro Vitale, Fabio Farinati, Mauro Borzio, Franco Trevisani, Umberto Cllo
we read with great interest the comment letter by Huo TI et al., since this letter gives us the possibility to better explain some aspects of the ITA.LI.CA prognostic system probably unclear in our previous studies. [1,2] First, the ITA.LI.CA system is a score based on 14 prognostic subgroups and not only 4: the lowest score (ITA.LI.CA score = 0) of the model corresponded to the best prognosis, and the highest score (ITA.LI.CA score = 13) was associated with the worst prognosis. This article is protected by copyright...
October 30, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30372785/mouse-models-of-nonalcoholic-steatohepatitis-towards-optimization-of-their-relevance-to-human-nash
#17
REVIEW
Geoff Farrell, Jörn M Schattenberg, Isabelle Leclercq, Matthew M Yeh, Robert Goldin, Narci Teoh, Detlef Schuppan
NASH arises from a variable interplay between environmental factors and genetic determinants that cannot be completely replicated in animals. Notwithstanding, preclinical models are needed to understand NASH pathophysiology and test mechanism-based therapies. Among several mouse models, some exhibit the key pathophysiologic as well as histopathologic criteria for human NASH, whereas others may be useful to address specific questions. Models based on over-nutrition with adipose restriction/inflammation and metabolic complications, particularly insulin resistance may be most useful to interrogate critical etiopathogenic factors...
October 29, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30372546/dap12-trem2-expression-by-mouse-and-human-liver-dc-functional-implications-and-regulation-of-liver-ischemia-reperfusion-injury
#18
Toshimasa Nakao, Yoshihiro Ono, Helong Dai, Ryosuke Nakano, Angelica Perez-Gutierrez, Geoffrey Camirand, Hai Huang, David A Geller, Angus W Thomson
Liver interstitial dendritic cells (DC) have been implicated in the control of ischemia/reperfusion injury (IRI) and host immune responses following liver transplantation. Mechanisms underlying these regulatory functions of hepatic DC remain unclear. We have shown recently that the transmembrane immunoadaptor DNAX-activating protein of 12 kDa (DAP12) negatively regulates mouse liver DC maturation and their pro-inflammatory and immune stimulatory functions. Here, we used PCR analysis and flow cytometry to characterize expression of DAP12 and its associated triggering receptor, triggering receptor expressed on myeloid cells 2 (TREM2) by mouse and human liver DC and other immune cells compared with DC in other tissues...
October 29, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30372542/commentary-for-hepatology-elsewhere-timely-administration-of-birth-dose-hbv-vaccine-may-break-the-chain-of-perinatal-transmission
#19
Aysha Aslam, Rizwan Ishtiaq, Daryl T Y Lau
This is a multicenter, double-blind, placebo-controlled clinical trial conducted in Thailand. A total of 331 HBeAg positive pregnant women with hepatitis B infection were randomly assigned to receive either TDF (n = 168) or placebo (n = 163) from 28 weeks of gestation to two months postpartum. Subjects with HIV or HCV coinfection were excluded. Standardized doses of HBIG (Grifols) and HBV vaccine (10 μg) at birth and one, two, four and six months were administered to the infants. The primary study endpoint was the HBV-positive status in the infants at six months after birth...
October 29, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/30372535/combined-hepatocellular-cholangiocarcinoma-in-a-patient-with-cirrhosis-due-to-cholesteryl-ester-storage-disease
#20
Graciela Elia Castro Narro, Armando Gamboa Domínguez, Alejandra Consuelo Sánchez, Abel Salazar Martínez, Jose Agramonte Hevia, J J Cebolla, Miguel Enrique Cuellar Mendoza, Héctor Adrián Díaz Hernández
Lysosomal acid lipase deficiency (LAL-D) results from different mutations in the lipase A (LIPA) gene and may result in two different phenotypes, the infantile-onset Wolman disease and the later onset cholesteryl ester storage disease (CESD). This enzyme defect results in accumulation of cholesteryl esters and triglycerides in the lysosomes of hepatocytes, Kupffer cells and other macrophage/monocyte cells causing multi-organ damage in the liver, spleen, blood vessels walls and gastrointestinal tract. To date, it has not been possible to establish a genotype/phenotype correlation, as this is a very rare disease, so reporting these cases is relevant to continue accumulating information on the behavior of this disease...
October 29, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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