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290 full-text articles. Page 6 of 14.

Vitamin D Deficiency Promotes Liver Tumor Growth In Transforming Growth Factor-Β/Smad3-Deficient Mice Through Wnt And Toll-Like Receptor 7 Pathway Modulation., Jian Chen, Lior H Katz, Nina M Muñoz, Shoujun Gu, Ji-Hyun Shin, Lopa Mishra, +13 additional authors 2016 George Washington University

Vitamin D Deficiency Promotes Liver Tumor Growth In Transforming Growth Factor-Β/Smad3-Deficient Mice Through Wnt And Toll-Like Receptor 7 Pathway Modulation., Jian Chen, Lior H Katz, Nina M Muñoz, Shoujun Gu, Ji-Hyun Shin, Lopa Mishra, +13 Additional Authors

Surgery Faculty Publications

Disruption of the TGF-β pathway is associated with liver fibrosis and suppression of liver tumorigenesis, conditions associated with low Vitamin D (VD) levels. However, potential contributions of VD to liver tumor progression in the context of TGF-β signaling remain unexplored. Our analyses of VD deprivation (VDD) in in vivo models of liver tumor formation revealed striking three-fold increases in tumor burden in Smad3(+/-) mice, with a three-fold increase in TLR7 expression compared to controls. ChIP and transcriptional assays confirm Smad3 binding at two TLR7 promoter SBE sites. Molecular interactions between TGF-β pathway and VDD were validated clinically, where an absence ...


Dc Beadm1™: Towards An Optimal Transcatheter Hepatic Tumour Therapy., Andrew L Lewis, Matthew R Dreher, Vincent O'Byrne, David Grey, Marcus Caine, Anthony Dunn, Yiqing Tang, Brenda Hall, Kirk D Fowers, Carmen Gacchina Johnson, Karun V. Sharma, Bradford J Wood 2016 George Washington University

Dc Beadm1™: Towards An Optimal Transcatheter Hepatic Tumour Therapy., Andrew L Lewis, Matthew R Dreher, Vincent O'Byrne, David Grey, Marcus Caine, Anthony Dunn, Yiqing Tang, Brenda Hall, Kirk D Fowers, Carmen Gacchina Johnson, Karun V. Sharma, Bradford J Wood

Pediatrics Faculty Publications

Clinical use of DC Bead™ loaded with doxorubicin (DEBDOX™) or irinotecan (DEBIRI™), for the treatment of primary and secondary tumours of the liver respectively, is showing great promise. Recently there has been a tendency to select smaller bead size ranges to treat tumours in an effort to allow more drug dose to be administered, improve tumoural penetration and resultant drug delivery and tumour coverage. Herein we describe the development and performance characterisation of a new DC Bead size range (DC BeadM1 (TM), 70-150 μm) capable of an increased bead delivery in the distal vasculature, corresponding to greater tumour coverage and ...


Exercise As The Best Treatment Option For Nafld, Amber Kirtley-Perez 2016 University of North Dakota

Exercise As The Best Treatment Option For Nafld, Amber Kirtley-Perez

Physician Assistant Scholarly Project Posters

Nonalcoholic fatty liver disease (NAFLD) is an advancing disease in children and adults that has the potential to be reversed. This disease is emerging in the population due to an increase in processed foods in the diet, increase in glucose intake in diet or liquid form, and lack of exercise. It is a growing epidemic in children that may progress into adulthood. The purpose of the literature review is to determine if the addition of daily exercise will decrease the amount of NAFLD and reverse the disease. The review of literature explored studies that are related to increasing exercise into ...


Efficacy Of Sofosbuvir, Velpatasvir, And Gs-9857 In Patients With Hepatitis C Virus Genotype 2, 3, 4, Or 6 Infections In An Open-Label, Phase 2 Trial, E. J. Gane, K. V. Kowdley, D. Pound, C. A.M. Stedman, M. Davis, K. Etzkorn, S. C. Gordon, D. Bernstein, P. Y. Kwo, M. H. Nguyen, +14 additional authors 2016 Zucker School of Medicine at Hofstra/Northwell

Efficacy Of Sofosbuvir, Velpatasvir, And Gs-9857 In Patients With Hepatitis C Virus Genotype 2, 3, 4, Or 6 Infections In An Open-Label, Phase 2 Trial, E. J. Gane, K. V. Kowdley, D. Pound, C. A.M. Stedman, M. Davis, K. Etzkorn, S. C. Gordon, D. Bernstein, P. Y. Kwo, M. H. Nguyen, +14 Additional Authors

Journal Articles

© 2016 AGA Institute Background & Aims Studies are needed to determine the optimal regimen for patients with chronic hepatitis C virus (HCV) genotype 2, 3, 4, or 6 infections whose prior course of antiviral therapy has failed, and the feasibility of shortening treatment duration. We performed a phase 2 study to determine the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in these patients. Methods We performed a multicenter, open-label trial at 32 sites in the United States and 2 sites in New Zealand from March 3, 2015 to April 27, 2015. Our study included 128 treatment-naïve and treatment-experienced patients (1 with HCV genotype 1b; 33 with HCV genotype 2; 74 with HCV genotype 3; 17 with genotype HCV 4; and 3 with HCV genotype 6), with or without compensated cirrhosis. All patients received sofosbuvir-velpatasvir (400 mg/100 mg fixed-dose combination tablet) and GS-9857 (100 mg) once daily for 6–12 weeks. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). Results After 6 weeks of treatment, SVR12s were achieved by 88% of treatment-naïve patients without cirrhosis (29 of 33; 95% confidence interval, 72%–97%). After 8 weeks of treatment, SVR12s were achieved by 93% of treatment-naïve ...


Modulation Of Body Weight By Intestinal Flora In Orphan Nuclear Receptor Shp-/- Mice, Ryan Mifflin 2016 University of Akron

Modulation Of Body Weight By Intestinal Flora In Orphan Nuclear Receptor Shp-/- Mice, Ryan Mifflin

Williams Honors College, Honors Research Projects

The whole-body deletion of small heterodimer partner (SHP) in mice is associated with protection from diet-induced obesity and hepatic steatosis upon feeding of a western diet. This protection was reported to be mediated through decreases in hepatic gene expression for lipogenesis, as well as increases in gene expression for fatty acid oxidation. SHP has been known to regulate the expression of the CYP7A1 gene, encoding the rate-limiting enzyme for bile acid synthesis, thereby altering the bile acid pool. The effects of this altered bile acid profile on the gut microbiome are unknown, as some bacteria in the gut are responsible ...


Expression Of The Non-Structural Proteins Ns3/4a Of The Hepatitis C Virus Using A Genetically Modified Vesicular Stomatitis Virus Vector System, Angela Ye Seul Kim 2016 Western University

Expression Of The Non-Structural Proteins Ns3/4a Of The Hepatitis C Virus Using A Genetically Modified Vesicular Stomatitis Virus Vector System, Angela Ye Seul Kim

2016 Undergraduate Awards

Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver diseases. Despite advancements in the development of antivirals and efforts to combat HCV infections, there is currently no vaccine for HCV. Adopting traditional approaches to HCV vaccine development has been impractical due to the lack of reproducible cell culture systems that can support HCV replication. In this study, the New Jersey serotype of recombinant vesicular stomatitis virus (rVSVNJ) was used as the vector to express non-structural proteins NS3/4A of genotype 1a HCV for potential vaccine purposes. The rVSVNJ-GMM vector was genetically modified by changing glycine ...


Efficacy Of Direct-Acting Antiviral Combination For Patients With Hepatitis C Virus Genotype 1 Infection And Severe Renal Impairment Or End-Stage Renal Disease, P. J. Pockros, K. R. Reddy, P. S. Mantry, E. Cohen, M. Bennett, M. S. Sulkowski, D. E. Bernstein, D. E. Cohen, N. S. Shulman, E. Lawitz, +4 additional authors 2016 Zucker School of Medicine at Hofstra/Northwell

Efficacy Of Direct-Acting Antiviral Combination For Patients With Hepatitis C Virus Genotype 1 Infection And Severe Renal Impairment Or End-Stage Renal Disease, P. J. Pockros, K. R. Reddy, P. S. Mantry, E. Cohen, M. Bennett, M. S. Sulkowski, D. E. Bernstein, D. E. Cohen, N. S. Shulman, E. Lawitz, +4 Additional Authors

Journal Articles

© 2016 AGA Institute. Background & Aims Although hepatitis C virus (HCV) infection is common in patients with end-stage renal disease, highly efficacious, well-tolerated, direct-acting antiviral regimens have not been extensively studied in this population. We investigated the safety and efficacy of ombitasvir co-formulated with paritaprevir and ritonavir, administered with dasabuvir (with or without ribavirin) in a prospective study of patients with stage 4 or 5 chronic kidney disease (CKD). Methods We performed a single-arm, multicenter study of treatment-naïve adults with HCV genotype 1 infection, without cirrhosis and with CKD stage 4 (estimated glomerular filtration rate, 15-30 mL/min/1.73 m2) or stage 5 (estimated glomerular filtration rate, /min/1.73 m2or requiring hemodialysis). Twenty patients were given ombitasvir co-formulated with paritaprevir and ritonavir, administered with dasabuvir for 12 weeks. Patients with HCV genotype 1a infections also received ribavirin (n = 13), whereas those with genotype 1b infection did not (n = 7). The primary end point was sustained virologic response (serum HCV RNA /mL) 12 weeks after treatment ended (SVR12). We collected data on on-treatment adverse events (AEs), serious AEs, and laboratory abnormalities. Results All 20 patients completed 12 weeks of treatment. Eighteen of the 20 patients achieved SVR12 (90%; 95% confidence interval: 69.9-97.2). One patient death after the end of the treatment (unrelated to the treatment) and 1 relapse accounted for the 2 non-SVRs. Adverse events were primarily mild or moderate, and no patient discontinued treatment due to an AE. Four patients experienced serious AEs; all were considered unrelated to treatment. Ribavirin therapy was interrupted in 9 patients due to anemia; 4 received erythropoietin. No blood transfusions were performed. Conclusions In a clinical trial, the combination of ombitasvir, paritaprevir, and ritonavir, administered with dasabuvir, led to an SVR12 in 90% of patients with ...


Simeprevir Plus Sofosbuvir (12 And 8 Weeks) In Hepatitis C Virus Genotype 1-Infected Patients Without Cirrhosis: Optimist-1, A Phase 3, Randomized Study, P. Kwo, N. Gitlin, R. Nahass, D. Bernstein, K. Etzkorn, S. Rojter, E. Schiff, M. Davis, P. Ruane, J. Witek, +8 additional authors 2016 Zucker School of Medicine at Hofstra/Northwell

Simeprevir Plus Sofosbuvir (12 And 8 Weeks) In Hepatitis C Virus Genotype 1-Infected Patients Without Cirrhosis: Optimist-1, A Phase 3, Randomized Study, P. Kwo, N. Gitlin, R. Nahass, D. Bernstein, K. Etzkorn, S. Rojter, E. Schiff, M. Davis, P. Ruane, J. Witek, +8 Additional Authors

Journal Articles

No abstract provided.


Protective Role Of Dietary Curcumin In The Prevention Of The Oxidative Stress Induced By Chronic Alcohol With Respect To Hepatic Injury And Antiatherogenic Markers, Ravi Varatharajalu, Mamatha Garige, Leslie C Leckey, Karina Reyes-Gordillo, Ruchi Shah, M. Raj Lakshman 2016 George Washington University

Protective Role Of Dietary Curcumin In The Prevention Of The Oxidative Stress Induced By Chronic Alcohol With Respect To Hepatic Injury And Antiatherogenic Markers, Ravi Varatharajalu, Mamatha Garige, Leslie C Leckey, Karina Reyes-Gordillo, Ruchi Shah, M. Raj Lakshman

Biochemistry and Molecular Medicine Faculty Publications

No abstract provided.


Should The Pharmacologic Management For Chronic Hepatitis C Encompass A Response Guided Therapy Treatment Plan?, Sarah Viscarra 2016 University of North Dakota

Should The Pharmacologic Management For Chronic Hepatitis C Encompass A Response Guided Therapy Treatment Plan?, Sarah Viscarra

Physician Assistant Scholarly Project Posters

Pharmacologic advances have been made with the development of new drug therapies that essentially cure the hepatitis C virus, such as sofosbuvir. The purpose of this study is to determine whether sofosbuvir should encompass a response guided therapy treatment plan versus a standard treatment protocol, in efforts to limit the risk of adverse effects and to minimize the cost of treatment. The systematic review of literature retrieved from Pub Med and Cochrane, explored studies that compared a standard treatment protocol of 12 weeks, in male and female adults ages 18-90 years, to response guided therapy treatment plans based on each ...


Voxel-Level Absorbed Dose Calculations With A Deterministic Grid-Based Boltzmann Solver For Nuclear Medicine And The Clinical Value Of Voxel-Level Calculations, Justin Mikell 2015 The University of Texas Graduate School of Biomedical Sciences at Houston

Voxel-Level Absorbed Dose Calculations With A Deterministic Grid-Based Boltzmann Solver For Nuclear Medicine And The Clinical Value Of Voxel-Level Calculations, Justin Mikell

UT GSBS Dissertations and Theses (Open Access)

Voxel-level absorbed dose (VLAD) is rarely calculated for nuclear medicine (NM) procedures involving unsealed sources or 90Y microspheres (YM). The current standard of practice for absorbed dose calculations in NM utilizes MIRD S-values, which 1) assume a uniform distribution in organs, 2) do not use patient specific geometry, and 3) lack a tumor model. VLADs overcome these limitations. One reason VLADs are not routinely performed is the difficulty in obtaining accurate absorbed doses in a clinically acceptable time. The deterministic grid-based Boltzmann solver (GBBS) was recently applied to radiation oncology where it was reported as fast and accurate for both ...


Detection Of Genetic And Epigenetic Dna Markers In Urine For The Early Detection Of Primary And Recurrent Hepatocellular Carcinoma, Hie-Won Hann, Surbhi Jain, Ting-Tsung Chang, Chi-Tan Hu, Selena Lin, Wei Song, Ying-Hsiu Su 2015 Thomas Jefferson University Hospital

Detection Of Genetic And Epigenetic Dna Markers In Urine For The Early Detection Of Primary And Recurrent Hepatocellular Carcinoma, Hie-Won Hann, Surbhi Jain, Ting-Tsung Chang, Chi-Tan Hu, Selena Lin, Wei Song, Ying-Hsiu Su

Division of Gastroenterology and Hepatology Posters

Poster presented at American Association of the Study of Liver Diseases (AASLD) meeting in San Francisco California.

Objective:

Develop a urine test using a panel of select genetic and epigenetic markers for the early detection of primary and recurrent HCC.

Introduction:

Hepatocellular carcinoma (HCC) or liver cancer is an aggressive disease and one of the fastest growing cancers by incidence in the United States. Early detection is the key for effective treatment of HCC as the 5-year survival rate is 26% in early stage HCC as compared to only 2% when found after spreading to distant organs. The current marker ...


A Prospective Analysis Of Factors Associated With Decreased Physical Activity In Patients With Cirrhosis Undergoing Transplant Evaluation, Anna Christina Dela Cruz, Valery Vilchez, Sooyeon Kim, Benjamin Barnes, Abhishek Ravinuthala, Anthony Zanni, Roberto Galuppo, Achuthan Sourianarayanane, Trushar Patel, Erin Colleen Maynard, Malay B. Shah, Michael F. Daily, Timothy L. Uhl, Karyn A. Esser, Roberto Gedaly 2015 University of Kentucky

A Prospective Analysis Of Factors Associated With Decreased Physical Activity In Patients With Cirrhosis Undergoing Transplant Evaluation, Anna Christina Dela Cruz, Valery Vilchez, Sooyeon Kim, Benjamin Barnes, Abhishek Ravinuthala, Anthony Zanni, Roberto Galuppo, Achuthan Sourianarayanane, Trushar Patel, Erin Colleen Maynard, Malay B. Shah, Michael F. Daily, Timothy L. Uhl, Karyn A. Esser, Roberto Gedaly

Internal Medicine Faculty Publications

BACKGROUND: Physical activity has been associated with improved recovery time after transplantation. Handgrip strength has been related to post-transplant outcomes.

AIM: To evaluate predictors of physical activity and grip strength in cirrhotic patients undergoing liver transplant evaluation.

METHODS: Single center, prospective analysis.

RESULTS: A hundred patients were evaluated (54% male, mean age 53 ± 9). Common etiologies of liver disease were non-alcoholic hepatitis (27%), hepatitis C (22%), and alcoholic liver disease (21%). Mean MELD score was 13.5. Forty one percent had a history of smoking. Ninety-three patients completed the International Physical Activity Questionnaire. The median total physical activity score of ...


A Rare Cause Of Obscure Occult Gastrointestinal Bleeding, Haroon Shahid, MD, Jason Korenblit, MD, MBA 2015 Department of Gastroenterology and Hepatology, Thomas Jefferson University Hospital

A Rare Cause Of Obscure Occult Gastrointestinal Bleeding, Haroon Shahid, Md, Jason Korenblit, Md, Mba

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND

  • Obscure gastrointestinal (GI) bleeding is defined as persistent or recurrent GI bleeding after negative evaluations with upper endoscopy and colonoscopy.
  • Accounts for approximately 5% of GI bleeding.
  • Obscure GI bleeding can further be classified as being overt or occult.

-Overt GI bleeding is clinically evident, with either hematemesis, hematochezia, or melena.

-Occult GI bleeding manifests as iron deficiency anemia or a positive fecal occult blood test.

  • Our case demonstrates a rare cause of obscure occult GI bleeding.


Regulation Of Metabolism By Hepatic Oxphos: A Dissertation, Thomas E. Akie 2015 University of Massachusetts Medical School

Regulation Of Metabolism By Hepatic Oxphos: A Dissertation, Thomas E. Akie

GSBS Dissertations and Theses

Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent issue in the modern world, predisposing patients to serious pathology such as cirrhosis and hepatocellular carcinoma. Mitochondrial dysfunction, and in particular, diminished hepatic oxidative phosphorylation (OXPHOS) capacity, have been observed in NAFLD livers, which may participate in NAFLD pathogenesis.

To examine the role of OXPHOS in NAFLD, we generated a model of enhanced hepatic OXPHOS using mice with liver-specific transgenic expression of LRPPRC, a protein which activates mitochondrial transcription and augments OXPHOS capacity. When challenged with high-fat feeding, mice with enhanced hepatic OXPHOS were protected from the development of liver steatosis ...


Increased Number Of Circulating Exosomes And Their Microrna Cargos Are Potential Novel Biomarkers In Alcoholic Hepatitis, Fatemeh Momen-Heravi, Banishree Saha, Karen Kodys, Donna Catalano, Abhishek Satishchandran, Gyongyi Szabo 2015 University of Massachusetts Medical School

Increased Number Of Circulating Exosomes And Their Microrna Cargos Are Potential Novel Biomarkers In Alcoholic Hepatitis, Fatemeh Momen-Heravi, Banishree Saha, Karen Kodys, Donna Catalano, Abhishek Satishchandran, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: It has been well documented that alcohol and its metabolites induce injury and inflammation in the liver. However, there is no potential biomarker to monitor the extent of liver injury in alcoholic hepatitis patients. MicroRNAs (miRNAs) are a class of non-coding RNAs that are involved in various physiologic and pathologic processes. In the circulation, a great proportion of miRNAs is associated with extracellular vesicles (EVs)/exosomes. Here, we hypothesized that the exosome-associated miRNAs can be used as potential biomarkers in alcoholic hepatitis (AH).

METHODS: Exosomes were isolated from sera of alcohol-fed mice or pair-fed mice, and plasma of alcoholic ...


Progression Of Non-Alcoholic Steatosis To Steatohepatitis And Fibrosis Parallels Cumulative Accumulation Of Danger Signals That Promote Inflammation And Liver Tumors In A High Fat-Cholesterol-Sugar Diet Model In Mice, Michal Ganz, Terence N. Bukong, Timea Csak, Banishree Saha, Jin-Kyu Park, Aditya Ambade, Karen Kodys, Gyongyi Szabo 2015 University of Massachusetts Medical School

Progression Of Non-Alcoholic Steatosis To Steatohepatitis And Fibrosis Parallels Cumulative Accumulation Of Danger Signals That Promote Inflammation And Liver Tumors In A High Fat-Cholesterol-Sugar Diet Model In Mice, Michal Ganz, Terence N. Bukong, Timea Csak, Banishree Saha, Jin-Kyu Park, Aditya Ambade, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming a pandemic. While multiple 'hits' have been reported to contribute to NAFLD progression to non-alcoholic steatohepatitis (NASH), fibrosis and liver cancer, understanding the natural history of the specific molecular signals leading to hepatocyte damage, inflammation and fibrosis, is hampered by the lack of suitable animal models that reproduce disease progression in humans. The purpose of this study was first, to develop a mouse model that closely mimics progressive NAFLD covering the spectrum of immune, metabolic and histopathologic abnormalities present in human disease; and second, to characterize the temporal relationship between sterile/exogenous ...


A Prospective Analysis Of Factors Associated With Decreased Physical Activity In Patients With Cirrhosis Undergoing Transplant Evaluation, Anna Christina Dela Cruz, Valery Vilchez, Sooyeon Kim, Benjamin Barnes, Abhishek Ravinuthala, Anthony Zanni, Roberto Galuppo, Achuthan Sourianarayanane, Trushar Patel, Erin Colleen Maynard, Malay B. Shah, Michael F. Daily, Timothy L. Uhl, Karyn A. Esser, Roberto Gedaly 2015 University of Kentucky

A Prospective Analysis Of Factors Associated With Decreased Physical Activity In Patients With Cirrhosis Undergoing Transplant Evaluation, Anna Christina Dela Cruz, Valery Vilchez, Sooyeon Kim, Benjamin Barnes, Abhishek Ravinuthala, Anthony Zanni, Roberto Galuppo, Achuthan Sourianarayanane, Trushar Patel, Erin Colleen Maynard, Malay B. Shah, Michael F. Daily, Timothy L. Uhl, Karyn A. Esser, Roberto Gedaly

Timothy L. Uhl

BACKGROUND: Physical activity has been associated with improved recovery time after transplantation. Handgrip strength has been related to post-transplant outcomes. AIM: To evaluate predictors of physical activity and grip strength in cirrhotic patients undergoing liver transplant evaluation. METHODS: Single center, prospective analysis. RESULTS: A hundred patients were evaluated (54% male, mean age 53 ± 9). Common etiologies of liver disease were non-alcoholic hepatitis (27%), hepatitis C (22%), and alcoholic liver disease (21%). Mean MELD score was 13.5. Forty one percent had a history of smoking. Ninety-three patients completed the International Physical Activity Questionnaire. The median total physical activity score of ...


Use Of Coronary Techniques In Celiac And Hepatic Artery Stenting In Post-Hepatic Transplant Patients, Harpreet Parmar, Ryan Beard, Mark W. Mewissen, Armaan Shaikh, Tanvir Bajwa 2015 Aurora Health Care

Use Of Coronary Techniques In Celiac And Hepatic Artery Stenting In Post-Hepatic Transplant Patients, Harpreet Parmar, Ryan Beard, Mark W. Mewissen, Armaan Shaikh, Tanvir Bajwa

Journal of Patient-Centered Research and Reviews

Hepatic artery stenosis (HAS) remains a rare but serious complication after liver transplantation. While invasive surgical techniques were needed for HAS treatment in the past, recently endovascular techniques, including hepatic artery stenting, have been proven to be a safe and effective treatment. The present work focused on a review of the recent literature regarding HAS as well as recent cases demonstrating the various presentations of HAS and the variety of approaches to endovascular intervention. Our single-center experience has shown endovascular treatment of HAS to be safe and effective, including the two specific cases discussed here. While further research is needed ...


Inhibition Of Sterile Danger Signals, Uric Acid And Atp, Prevents Inflammasome Activation And Protects From Alcoholic Steatohepatitis In Mice., Arvin Iracheta-Vellve, Jan Petrasek, Abhishek Satishchandran, Benedek Gyongyosi, Banishree Saha, Karen Kodys, Katherine Fitzgerald, Evelyn Kurt-Jones, Gyongyi Szabo 2015 University of Massachusetts Medical School Worcester

Inhibition Of Sterile Danger Signals, Uric Acid And Atp, Prevents Inflammasome Activation And Protects From Alcoholic Steatohepatitis In Mice., Arvin Iracheta-Vellve, Jan Petrasek, Abhishek Satishchandran, Benedek Gyongyosi, Banishree Saha, Karen Kodys, Katherine Fitzgerald, Evelyn Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

Background & Aims: The inflammasome is a well-characterized inducer of inflammation in alcoholic steatohepatitis (ASH). Inflammasome activation requires two signals for mature interleukin (IL)-1β production. Here we asked whether metabolic danger signals trigger inflammasome activation in ASH.

Results:The sterile danger signals, ATP and uric acid, were increased in the serum and liver of alcohol-fed mice. Depletion of uric acid or ATP, or lack of ATP signaling attenuated ASH and prevented inflammasome activation and its major downstream cytokine, IL-1β. Pharmacological depletion of uric acid with allopurinol provided significant protection from alcohol-induced inflammatory response, steatosis and liver damage, and additional protection ...


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