Hepatology Commons^™

Hypoxia-Inducible Factor (Hif)-2Α Reprograms Liver Macrophages To Protect Against Acute Liver Injury Via The Production Of Interleukin-6, Rachel Y Gao, Meng Wang, Qihui Liu, Dechun Feng, Yankai Wen, Yang Xia, Sean P Colgan, Holger K Eltzschig, Cynthia Ju

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Acetaminophen (APAP) overdose represents the most frequent cause of acute liver failure, resulting in death or liver transplantation in more than one third of patients in the United States. The effectiveness of the only antidote, N-acetylcysteine, declines rapidly after APAP ingestion, long before patients are admitted to the clinic with symptoms of severe liver injury. The direct hepatotoxicity of APAP triggers a cascade of innate immune responses that may exacerbate or limit the progression of tissue damage. A better understanding of this complex mechanism will help uncover targets for therapeutic interventions.

APPROACH AND RESULTS: We observed that …

Outcomes Of Patients Hospitalized With Community-Acquired Pneumonia With Liver Disease Or Cirrhosis., Bibodh Jung Karki, Sravan K. Ponnekanti, Vidyulata Salunkhe, Nishita Tripathi, Mahder A. Tella, Stephen P. Furmanek, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

Introduction: Liver disease and cirrhosis are common causes of mortality worldwide. Community-acquired pneumonia is recognized as a significant cause of morbidity and mortality in this population of adults. There is a lack of data regarding outcomes or prognosis in patients with liver dysfunction who develop CAP. The objective of this study was to evaluate the clinical characteristics, incidence, and outcomes of hospitalized patients with CAP and liver disease.

Methods: This was a secondary analysis of the University of Louisville Pneumonia Study, which was a prospective population-based cohort study of adults hospitalized with community-acquired pneumonia. All patients were divided into three …

Alternative Splicing Of The Slco1b1 Gene: An Exploratory Analysis Of Isoform Diversity In Pediatric Liver., Bianca D. Van Groen, Chengpeng Bi, Roger Gaedigk, Vincent S. Staggs, Dick Tibboel, Saskia N. De Wildt, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

The hepatic influx transporter OATP1B1 (SLCO1B1) plays an important role in the disposition of endogenous substrates and drugs prescribed to children. Alternative splicing increases the diversity of protein products from > 90% of human genes and may be triggered by developmental signals. As concentrations of several endogenous OATP1B1 substrates change during growth and development, with this exploratory study we investigated age-dependent alternative splicing of SLCO1B1 mRNA in 97 postmortem livers (fetus-adolescents). Twenty-seven splice variants were detected; 10 were confirmed by additional bioinformatic analyses and verified by quantitative polymerase chain reaction, and selected for detailed analysis based on relative abundance, association with …

A Descriptive Study Of Racial Inequalities In Mortality From Hepatocellular Cancer Before And After Licensure Of Lifesaving Drugs For Hepatitis C Virus In The United States, Robert S Levine, Maria C Mejia, Jason L Salemi, Sandra J Gonzalez, Muktar H Aliyu, Baqar A Husaini, Roger J Zoorob, Charles H Hennekens

Faculty, Staff and Students Publications

BACKGROUND: Since 1979, mortality from hepatocellular cancer (HCC) has doubled in the United States (US). Lifesaving drugs, prohibitively expensive for some, were approved and marketed to treat hepatitis C virus (HCV), a major risk factor for HCC, beginning in 1997. After the prior introduction of other lifesaving innovations, including active retroviral drug therapy for human immunodeficiency virus and surfactant for respiratory distress syndrome of the newborn, racial inequalities in their mortalities increased in the US. In this descriptive study, we explored racial inequalities in mortality from HCC before and after licensure of HCV drugs in the US.

METHODS: The US …

An Investigation Of Acute Effects At Various Doses Of Malathion On Glucose Homeostasis And Insulin Resistance In Rat Liver, Pancreas And Serum, Murat Ekremoğlu, Çınar Severcan, Özge Tuğce Pasaoğlu, Bayram Şen, Hatice Pasaoğlu

Journal of Mind and Medical Sciences

Objective. This study investigates acute effects of various doses of Malathion on glucose homeostasis and insulin resistance in rat.

Methods. Rats were randomly divided into four groups of 6 animals each. Corn oil was given orally to Group 1. Group 2, Group 3, and Group 4 received malathion dissolved in corn oil via oral administration at the doses of 100, 200 and 400 mg/kg, respectively. 24 hours later the rats were sacrificed.

Results. Acute administration of Malathion led to a decrease in serum butryl cholinesterase (BChE) levels at all doses tested. It also caused a significant increase in serum advanced …

Provider Attitudes And Practice Patterns For Direct-Acting Antiviral Therapy For Patients With Hepatocellular Carcinoma, Nicole E Rich, Ju Dong Yang, Ponni V Perumalswami, Naim Alkhouri, Whitney Jackson, Neehar D Parikh, Neil Mehta, Reena Salgia, Andres Duarte-Rojo, Laura Kulik, Mina Rakoski, Adnan Said, Omobonike Oloruntoba, George N Ioannou, Maarouf A Hoteit, Andrew M Moon, Amol S Rangnekar, Sheila L Eswaran, Elizabeth Zheng, Janice H Jou, James Hanje, Anjana Pillai, Ruben Hernaez, Robert Wong, Steven Scaglione, Hrishikesh Samant, Devika Kapuria, Shaun Chandna, Russell Rosenblatt, Veeral Ajmera, Catherine T Frenette, Sanjaya K Satapathy, Parvez Mantry, Prasun Jalal, Binu V John, Oren K Fix, Michael Leise, Christina C Lindenmeyer, Avegail Flores, Nayan Patel, Z Gordon Jiang, Nyan Latt, Renumathy Dhanasekaran, Mobolaji Odewole, Sofia Kagan, Jorge A Marrero, Amit G Singal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are effective against hepatitis C virus and sustained virologic response is associated with reduced incidence of hepatocellular carcinoma (HCC). However, there is controversy over the use of DAAs in patients with active or treated HCC and uncertainty about optimal management of these patients. We aimed to characterize attitudes and practice patterns of hepatology practitioners in the United States regarding the use of DAAs in patients with HCC.

METHODS: We conducted a survey of hepatology providers at 47 tertiary care centers in 25 states. Surveys were sent to 476 providers and we received 279 responses …

Hepatitis B Virus Hbx Protein Mediates The Degradation Of Host Restriction Factors Through The Cullin 4 Ddb1 E3 Ubiquitin Ligase Complex, Marissa M Minor, F Blaine Hollinger, Adrienne L Mcnees, Sung Yun Jung, Antrix Jain, Joseph M Hyser, Karl-Dimiter Bissig, Betty L Slagle

Faculty, Staff and Students Publications

The hepatitis B virus (HBV) regulatory HBx protein is required for infection, and its binding to cellular damaged DNA binding protein 1 (DDB1) is critical for this function. DDB1 is an adaptor protein for the cullin 4A Really Interesting New Gene (RING) E3 ubiquitin ligase (CRL4) complex and functions by binding cellular DDB1 cullin associated factor (DCAF) receptor proteins that recruit substrates for ubiquitination and degradation. We compared the proteins found in the CRL4 complex immunoprecipitated from uninfected versus HBV-infected hepatocytes from human liver chimeric mice for insight into mechanisms by which HBV and the cell interact within the CRL4 …

Primary Sclerosing Cholangitis: Epidemiology, Genetics, Diagnosis, And Current Management., Eric Gochanour, Channa Jayasekera, Kris V Kowdley

Articles, Abstracts, and Reports

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-reading-gochanour a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-interview-kowdley an interview with the author.

Methyl-Sensing Nuclear Receptor Liver Receptor Homolog-1 Regulates Mitochondrial Function In Mouse Hepatocytes, Sungwoo Choi, Bingning Dong, Chih-Chun Janet Lin, Mi Jeong Heo, Kang Ho Kim, Zhen Sun, Martin Wagner, Nagireddy Putluri, Jae Myoung Suh, Meng C Wang, David D Moore

Faculty, Staff and Students Publications

Liver receptor homologue-1 (LRH-1; NR5A2) is a nuclear receptor that regulates metabolic homeostasis in the liver. Previous studies identified phosphatidylcholines as potential endogenous agonist ligands for LRH-1. In the liver, distinct subsets of phosphatidylcholine species are generated by two different pathways: choline addition to phosphatidic acid via the Kennedy pathway, or trimethylation of phosphatidylethanolamine via Phosphatidylethanolamine N-methyl Transferase (PEMT). Here we report that a PEMT - LRH-1 pathway specifically couples methyl metabolism and mitochondrial activities in hepatocytes. We show that the loss of Lrh-1 reduces mitochondrial number, basal respiration, beta-oxidation and ATP production in hepatocytes, and decreases expression of mitochondrial …

Hyperammonemic Encephalopathy With Triphasic Waves: A Case, Brian Birdsong, Brielle Marks, Rishim Jayswal, Adeel Rahman

Psychiatry

No abstract provided.

The Overall Poor Specificity Of Mrcp In The Preoperative Evaluation Of The Jaundiced Patient Will Increase The Incidence Of Non-Therapeutic Ercp, Andrew M. O'Neill Md, Keith Anderson Md, Lorinda K. Baker, Michaal Schurr Md

General Surgery

See additional files.

The Role Of Noninvasive Tests For Differentiating Nash From Nafl And Diagnosing Advanced Fibrosis Among Patients With Nafld, Maya Balakrishnan, Rohit Loomba

Faculty, Staff and Students Publications

Assessing for the presence of non-alcoholic steatohepatitis (NASH) and the presence of advanced fibrosis is vital among patients with non-alcoholic fatty liver disease (NAFLD) as each is predictive of disease outcomes. A liver biopsy is the gold standard method for doing so but is impossible to perform among all patients with NAFLD. Reliable methods for noninvasively detecting for the presence of NASH and advanced fibrosis are thus a pressing need. The search for noninvasive tests has been more successful for advanced fibrosis than for NASH. Clinical prediction models and elastography have acceptable accuracy for ruling out advanced fibrosis; when used …

Tumor Slice Culture As A Biologic Surrogate Of Human Cancer., Heidi L Kenerson, Kevin M Sullivan, Yongwoo D Seo, Kathryn M Stadeli, Cigdem Ussakli, Xiaowei Yan, Christopher G Lausted, Venu G Pillarisetty, James O Park, Kimberly J Riehle, Matthew Yeh, Qiang Tian, Raymond S Yeung

Articles, Abstracts, and Reports

Background: The tumor microenvironment (TME) is critical to every aspect of cancer biology. Organotypic tumor slice cultures (TSCs) preserve the original TME and have demonstrated utility in predicting drug sensitivity, but the association between clinicopathologic parameters and

Methods: One hundred and eight fresh tumor specimens from liver resections at a tertiary academic center were procured and precisely cut with a Vibratome to create 250 μm × 6 mm slices. These fixed-dimension TSCs were grown on polytetrafluoroethylene inserts, and their metabolic activities were determined by a colorimetric assay. Correlation between baseline activities and clinicopathologic parameters was assessed. Tissue CEA mRNA expression …

Methylation Signatures In Peripheral Blood Are Associated With Marked Age Acceleration And Disease Progression In Patients With Primary Sclerosing Cholangitis., Michael Trauner, Yevgeniy Gindin, Zhaoshi Jiang, Chuhan Chung, G Mani Subramanian, Robert P Myers, Aliya Gulamhusein, Kris V Kowdley, Cynthia Levy, Zachary Goodman, Michael P Manns, Andrew J Muir, Christopher L Bowlus

Articles, Abstracts, and Reports

Background & Aims: A DNA methylation (DNAm) signature derived from 353 CpG sites (the Horvath clock) has been proposed as an epigenetic measure of chronological and biological age. This epigenetic signature is accelerated in diverse tissue types in various disorders, including non-alcoholic steatohepatitis, and is associated with mortality. Here, we assayed whole blood DNAm to explore age acceleration in patients with primary sclerosing cholangitis (PSC).

Methods: Using the MethylationEPIC BeadChip (850K) array, DNAm signatures in whole blood were analyzed in 36 patients with PSC enrolled in a 96-week trial of simtuzumab (Ishak F0-1, n = 13; F5-6, n = 23). …

Peri-Transplant Management Of Nonalcoholic Fatty Liver Disease In Liver Transplant Candidates, N. S. Samji, R. Heda, S. K. Satapathy

Journal Articles

© Translational Gastroenterology and Hepatology. All rights reserved. The incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly growing, affecting 25% of the world population. Non-alcoholic steatohepatitis (NASH) is the most severe form of NAFLD and affects 1.5% to 6.5% of the world population. Its rising incidence will make end-stage liver disease (ESLD) due to NASH the number one indication for liver transplantation (LT) in the next 10 to 20 years, overtaking Hepatitis C. Patients with NASH also have a high prevalence of associated comorbidities such as type 2 diabetes, obesity, metabolic syndrome, cardiovascular disease, and chronic kidney disease (CKD), …

Role Of Nutraceuticals In Covid-19 Mediated Liver Dysfunction., M. Sikander, S. Malik, A. Rodriguez, M. M. Yallapu, A. S. Narula, S. K. Satapathy, V. Dhevan, S. C. Chauhan, M. Jaggi

Journal Articles

COVID-19 is known as one of the deadliest pandemics of the century. The rapid spread of this deadly virus at incredible speed has stunned the planet and poses a challenge to global scientific and medical communities. Patients with COVID-19 are at an increased risk of co-morbidities associated with liver dysfunction and injury. Moreover, hepatotoxicity induced by antiviral therapy is gaining importance and is an area of great concern. Currently, alternatives therapies are being sought to mitigate hepatic damage, and there has been growing interest in the research on bioactive phytochemical agents (nutraceuticals) due to their versatility in health benefits reported …

Association Between Longer Hospitalization And Development Of De Novo Donor Specific Antibodies In Simultaneous Liver–Kidney Transplant Recipients, M. Yazawa, O. Cseprekal, R. A. Helmick, M. Talwar, V. Balaraman, P. S. Podila, S. Fossey, S. K. Satapathy, J. D. Eason, M. Z. Molnar

Journal Articles

© 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Background:De novo Donor Specific Antibodies (DSA) are considered as a risk factor for the kidney allograft outcomes in recipients after simultaneous liver–kidney transplantation (SLKT). We hypothesized that length of hospital stay (LOS) might be associated with de novo DSA development of due to the increased likelihood of receiving blood transfusions with reduced immunosuppressive regimens. Methods: This study is a single-center, retrospective cohort study consisting of 85 recipients who underwent SLKT from 2009 to 2018 in our hospital. We divided the patients into two …

Prevalence And Profile Of Nonalcoholic Fatty Liver Disease In Lean Adults: Systematic Review And Meta-Analysis., S. Young, R. Tariq, J. Provenza, S. K. Satapathy, K. Faisal, A. Choudhry, S. L. Friedman, A. K. Singal

Journal Articles

Data on prevalence and profile of nonalcoholic fatty liver disease (NAFLD) among individuals who are lean (normal body mass index) is unclear. Published data from studies comparing lean with obese NAFLD or with healthy subjects on prevalence, comorbidities, liver chemistry and histology, and metabolic/inflammatory markers were analyzed. Data were reported as odds ratio and 95% confidence interval for categorical variables and difference of means for continuous variables. Analysis of 53 studies on 65,029 subjects with NAFLD (38,084 lean) and 249,544 healthy subjects showed a prevalence of lean NAFLD at 11.2% in the general population. Among individuals with NAFLD, the prevalence …

Outcomes Of Liver Transplant Recipients With Acute-On-Chronic Liver Failure Based On Easl-Clif Consortium Definition: A Single-Center Study, U. Agbim, A. Sharma, B. Maliakkal, S. Karri, M. Yazawa, W. Goldkamp, P. S. Podila, J. M. Vanatta, H. Gonzalez, S. K. Satapathy, +3 Additional Authors

Journal Articles

© 2020 Cambridge University Press. All rights reserved. Background. The impact of acute-on-chronic liver failure (ACLF) defined by European Association for the Study of the Liver-Chronic Liver Failure in liver transplant (LT) recipients has not been well characterized. The aim of the study was to assess early posttransplant morbidity and survival of ACLF patients. Methods. Eight hundred twenty-five consecutive LT patients (04/2006-03/2013) were included in a retrospective analysis. Of the 690 evaluable patients, 589 had no ACLF, and the remaining 101 were grouped into ACLF Grades 1-3 (ACLF Grade 1: 50 [49.5%], ACLF Grade 2: 32 [31.7%], and ACLF Grade …

Nafld Epidemiology, Emerging Pharmacotherapy, Liver Transplantation Implications And The Trends In The United States, C. Gadiparthi, M. Spatz, S. Greenberg, U. Iqbal, S. Kanna, S. K. Satapathy, A. Broder, A. Ahmed

Journal Articles

© 2020 Authors. Nonalcoholic fatty liver disease (NAFLD) is a hepatic mani-festation of metabolic syndrome. The spread of obesity worldwide in pandemic proportions has led to a rapid rise of NAFLD in developed and developing countries alike. There are no approved pharmacological agents to treat steatohepatitis or advanced fibrosis but obeticholic acid recently has shown some promise in phase III trial. Currently, NAFLD is the number one etiology for simultaneous liver and kidney transplantation in the USA, second most common indication for liver transplantation (LT) and projected to become number one very soon. LT for NAFLD poses unique challenges, as …