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Full-Text Articles in Hepatology

Evaluation Of Awareness, Knowledge, And Preventive Intervention Of Nonalcoholic Fatty Liver Disease Among Chinese Young Adults, Yi Du May 2022

Evaluation Of Awareness, Knowledge, And Preventive Intervention Of Nonalcoholic Fatty Liver Disease Among Chinese Young Adults, Yi Du

Theses & Dissertations

The prevalence of nonalcoholic fatty liver disease (NAFLD) among Chinese young adults (CYA) aged 18-25 years ranges from 4.7% to 15.1% and has kept increasing in recent years. Previous studies reported limited awareness and knowledge of NALFD among middle-aged and older Chinese populations, however, they have not investigated awareness in CYA, for which there is no well-validated questionnaire. There is currently no efficacious educational intervention on NAFLD for CYA.

The objectives were 1) to develop and validate a questionnaire which can be used to assess the awareness and knowledge of NAFLD among CYA; 2) to assess the awareness and knowledge …


Impact Of Compensated Cirrhosis On Survival In Patients With Acute-On-Chronic Liver Failure, Kessarin Thanapirom, Tongluk Teerasarntipan, Sombat Treeprasertsuk, Ashok Choudhury, Manoj K. Sahu, Rakhi Maiwall, Viniyendra Pamecha, Richard Moreau, Saeed Hamid, Amna Subhan Butt Nov 2021

Impact Of Compensated Cirrhosis On Survival In Patients With Acute-On-Chronic Liver Failure, Kessarin Thanapirom, Tongluk Teerasarntipan, Sombat Treeprasertsuk, Ashok Choudhury, Manoj K. Sahu, Rakhi Maiwall, Viniyendra Pamecha, Richard Moreau, Saeed Hamid, Amna Subhan Butt

Section of Gastroenterology

Background and aims: Acute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database.
Methods: A total of 1,621 patients were prospectively enrolled and 637 (39.3%) of these patients had cirrhosis. Baseline characteristics, complications and mortality were compared between patients with and without cirrhosis.
Results: Alcohol consumption was more common in cirrhosis than non-cirrhosis (66.4% vs. 44.2%, p < 0.0001), while non-alcoholic fatty liver disease/cryptogenic CLD (10.9% vs 5.8%, p < 0.0001) and chronic HBV reactivation (18.8% vs 11.8%, p < 0.0001) were more common in non-cirrhosis. Only 0.8% of patients underwent liver transplantation. Overall, 28-day and 90-day mortality rates were 39.3% and 49.9%, respectively. Patients with cirrhosis had a greater chance of survival compared to those without cirrhosis both at 28-day (HR = 0.48; 95% CI 0.36-0.63, p < 0.0001) and 90-day (HR = 0.56; 95% CI 0.43-0.72, p < 0.0001), respectively. In alcohol CLD, non-cirrhosis patients had a higher 28-day (49.9% vs. 23.6%, p < 0.001) and 90-day (58.4% vs. 35.2%, p < 0.001) mortality rate than cirrhosis patients. ACLF patients with cirrhosis had longer mean survival than non-cirrhosis patients (25.5 vs. 18.8 days at 28-day and 65.2 vs. 41.2 days at 90-day). Exaggerated systemic inflammation might be the reason why non-cirrhosis patients had a poorer prognosis than those with cirrhosis after ACLF had occurred.
Conclusions: The 28-day and 90-day mortality rates of ACLF patients without cirrhosis were …


Health And Economic Benefits Of Achieving Hepatitis C Virus Elimination In Pakistan: A Modelling Study And Economic Analysis, Aaron G. Lim, Nick Scott, Josephine G. Walker, Saeed Hamid, Margaret Hellard, Peter Vickerman Oct 2021

Health And Economic Benefits Of Achieving Hepatitis C Virus Elimination In Pakistan: A Modelling Study And Economic Analysis, Aaron G. Lim, Nick Scott, Josephine G. Walker, Saeed Hamid, Margaret Hellard, Peter Vickerman

Section of Gastroenterology

Background: Modelling suggests that achieving the WHO incidence target for hepatitis C virus (HCV) elimination in Pakistan could cost US$3.87 billion over 2018 to 2030. However, the economic benefits from integrating services or improving productivity were not included.
Methods and findings: We adapt a HCV transmission model for Pakistan to estimate the impact, costs, and cost-effectiveness of achieving HCV elimination (reducing annual HCV incidence by 80% by 2030) with stand-alone service delivery, or partially integrating one-third of initial HCV testing into existing healthcare services. We estimate the net economic benefits by comparing the required investment in screening, treatment, and healthcare …


Hepatitis E: Genotypes, Strategies To Prevent And Manage, And The Existing Knowledge Gaps, Lubna Kamani, Zahra Ali Padhani, Jai K. Das Aug 2021

Hepatitis E: Genotypes, Strategies To Prevent And Manage, And The Existing Knowledge Gaps, Lubna Kamani, Zahra Ali Padhani, Jai K. Das

Section of Gastroenterology

Hepatitis E virus (HEV) is considered an emergent source of viral hepatitis worldwide, with an increasing burden of jaundice, liver failure, extrahepatic illnesses, and deaths in developed countries. With the scarcity of data from efficient animal models, there are still open-ended questions about designing new models to study pathogenesis, types, virology, and evolution of these viruses. With an emphasis on available data and updates, there is still enough information to understand the HEV life cycle, pathogen interaction with the host, and the valuation of the role of vaccine and new anti-HEV therapies. However, the World Health Organization (WHO) and the …


Malnutrition And Liver Disease In A Developing Country, Asra Tus Saleha Siddiqui, Om Parkash, Syeda Amrah Hashmi Aug 2021

Malnutrition And Liver Disease In A Developing Country, Asra Tus Saleha Siddiqui, Om Parkash, Syeda Amrah Hashmi

Section of Gastroenterology

Malnutrition is a highly prevalent and under recognized condition in developing countries of South Asia. The presence of malnutrition causes a severe impact on patients with liver cirrhosis. The etiology of cirrhosis differs in the South Asian region compared to the West, with hepatitis B and C still being the leading causes and the prevalence of nonalcoholic fatty liver disease increasing over time. Comorbid malnutrition worsens outcomes for cirrhosis patients. Urgent attention to address malnutrition is needed to improve patient outcomes. The etiology and pathophysiology of malnutrition in liver diseases is multifactorial, as reduction in liver function affects both macronutrients …


Interventional Treatment With The Transjugular Intrahepatic Portosystemic Shunt (Tips) Procedure May Offer A Preferable Alternative To Systemic Anticoagulation In Patients With Cirrhosis And Portal Vein Thrombosis, Molly N. Pantelic May 2021

Interventional Treatment With The Transjugular Intrahepatic Portosystemic Shunt (Tips) Procedure May Offer A Preferable Alternative To Systemic Anticoagulation In Patients With Cirrhosis And Portal Vein Thrombosis, Molly N. Pantelic

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Wang Z, Jiang MS, Zhang HL, et al. Is post-tips anticoagulation therapy necessary in patients with cirrhosis and portal vein thrombosis? A randomized controlled trial. Radiology. 2016;279(3):943-951. https://doi.org/10.1148/radiol.2015150369

for a patient with cryptogenic cirrhosis, gastroesophageal varices, pancreatic cancer, and portal vein thrombosis.


Updates On The Diagnosis And Management Of Hepatocellular Carcinoma, Aimun Raees, Muhammad Kamran, Hasan Özkan, Wasim Jafri Jan 2021

Updates On The Diagnosis And Management Of Hepatocellular Carcinoma, Aimun Raees, Muhammad Kamran, Hasan Özkan, Wasim Jafri

Section of Gastroenterology

Introduction: Globally, the incidence, as well as mortality, related to hepatocellular carcinoma (HCC) is on the rise, owing to relatively few curative options. Underlying cirrhosis is the most common etiology leading to HCC, but risk factors of cirrhosis show great regional variability. Over the years, there has been a steady development in the diagnostic and therapeutic modalities of HCC, including the availability of a wide range of systemic chemotherapeutic agents. We aim to review the recent advancements in the diagnostic and therapeutic strategies for HCC.
Methodology: The literature search was done using databases PubMed, Cochrane, and Science Direct, and the …


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 Feb 2020

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.


Acute Diagnosis Of Wilson’S Disease In A Teenage Patient, Sarah Irvin, Ryan Mccarthy Oct 2019

Acute Diagnosis Of Wilson’S Disease In A Teenage Patient, Sarah Irvin, Ryan Mccarthy

Marshall Journal of Medicine

Wilson’s Disease, a rare autosomal recessive genetic disease, is caused by a mutation in the ATP7B enzyme gene. Without this enzyme, copper builds up in the brain, liver, and cornea causing a multitude of symptoms. It is important to consider Wilson’s disease because the prognosis is dependent on timely diagnosis. This is an interesting case of a 19-year-old male who presented with suicidal thoughts and rapid weight loss. After many months and an extensive work-up, Wilson’s Disease was diagnosed. Due to his rapid decline, he was transferred to a larger university healthcare center where he is currently enrolled in clinical …


Proton Pump Inhibitors Increase The Severity Of Hepatic Encephalopathy In Cirrhotic Patients, Matthew J. Fasullo, Prashanth Rau, Dong-Qi Liu, Erik Holzwanger, Jomol Mathew, Yurima Guilarte-Walker, Gyongyi Szabo Aug 2019

Proton Pump Inhibitors Increase The Severity Of Hepatic Encephalopathy In Cirrhotic Patients, Matthew J. Fasullo, Prashanth Rau, Dong-Qi Liu, Erik Holzwanger, Jomol Mathew, Yurima Guilarte-Walker, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites, esophageal/gastric varices or encephalopathy. The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy (HE). Well established triggers for HE include infection, gastrointestinal bleeding, constipation, and medications. Alterations to the gut microbiome is one of the leading ammonia producers in the body, and therefore may make patients more susceptible to HE.

AIM: To investigate the relationship between the use of proton pump inhibitors (PPIs) and HE …


Segmental Distribution Of Hepatocellular Carcinoma Correlates With Microvascular Invasion In Liver Explants Undergoing Transplantation, Yasir Al-Azzawai, Eva Rouanet, Ryan J. Hendrix, Lidia Spaho, Hesham Malik, Deepika Devuni, Gyongyi Szabo, Graham Barnard Jul 2019

Segmental Distribution Of Hepatocellular Carcinoma Correlates With Microvascular Invasion In Liver Explants Undergoing Transplantation, Yasir Al-Azzawai, Eva Rouanet, Ryan J. Hendrix, Lidia Spaho, Hesham Malik, Deepika Devuni, Gyongyi Szabo, Graham Barnard

Gyongyi Szabo

Introduction: Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients is a poor prognostic factor after liver transplantation and/or resection. Any correlation between MVI and segmental location of HCC has yet to be studied. Our aim is to evaluate the segmental location of HCC and any correlation with the presence of MVI, portal vein thrombosis (PVT) in explanted livers, and the recurrence of HCC after transplantation. Another objective of the study is to assess the treatment history (ablation or transarterial chemoembolization (TACE)) and size of the tumor with respect to the risk of MVI.

Methods: A single center, retrospective chart review, …


Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin May 2019

Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin

Electronic Theses and Dissertations

Background. Ethanol (EtOH) consumption is known to affect multiple organs; this is unsurprising, as the concentration of EtOH in the blood at relevant doses reaches the millimolar range. The overarching goal of this dissertation was to elucidate mechanisms of alcohol-induced organ injury, specifically the effects of alcohol on the hepatic extracellular matrix (ECM) proteome, the alcoholic hepatitis (AH) plasma peptidome, and the effects of alcohol on the renal cortex proteome and transcriptome. Methods. Mice were pair-fed ethanol-containing liquid diet chronically, and then some mice were administered lipopolysaccharide (LPS). Liver sections from these mice were processed in a series of increasingly …


Extracellular Vesicles In Liver Diseases: Meeting Report From The International Liver Congress 2018, Jesus M. Banales, Ariel E. Feldstein, Hanna Sanger, Veronika Lukacs-Kornek, Gyongyi Szabo, Miroslaw Kornek Mar 2019

Extracellular Vesicles In Liver Diseases: Meeting Report From The International Liver Congress 2018, Jesus M. Banales, Ariel E. Feldstein, Hanna Sanger, Veronika Lukacs-Kornek, Gyongyi Szabo, Miroslaw Kornek

Gyongyi Szabo

Extracellular vesicles (EVs) are small and heterogeneous membrane-bound structures released by cells and found in all biological fluids. They are effective intercellular communicators, acting on a number of close and/or distant target cells. EV cargo may reflect the cell of origin as well as the specific stress that induces their formation and release. They transport a variety of bioactive molecules, including messenger RNA, noncoding RNAs, proteins, lipids, and metabolites, that can be transferred among cells, regulating various cell responses. Alteration in the concentration and composition of EVs in biological fluids is a typical hallmark of pathologies in different liver diseases. …


Inhibition Of Triggering Receptor Expressed On Myeloid Cells 1 Ameliorates Inflammation And Macrophage And Neutrophil Activation In Alcoholic Liver Disease In Mice, David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo Mar 2019

Inhibition Of Triggering Receptor Expressed On Myeloid Cells 1 Ameliorates Inflammation And Macrophage And Neutrophil Activation In Alcoholic Liver Disease In Mice, David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo

Gyongyi Szabo

Alcoholic liver disease (ALD) is characterized by macrophage and neutrophil leukocyte recruitment and activation in the liver. Damage- and pathogen-associated molecular patterns contribute to a self-perpetuating proinflammatory state in ALD. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a surface receptor that amplifies inflammation induced by toll-like receptors (TLRs) and is expressed on neutrophils and monocytes/macrophages. We hypothesized that TREM-1 signaling contributes to proinflammatory pathway activation in ALD. Using an in vivo ALD model in mice, we tested the effects of ligand-independent TREM-1 inhibitory peptides that were formulated into human high-density lipoprotein (HDL)-mimicking complexes GF9-HDL and GA/E31-HDL. As revealed …


Aortoduodenal Fistula Forms From Primary Aortic Stump Graft In A Two-Time Multi-Visceral Transplant Patient With Presentation Of Gastrointestinal Bleed And Bowel Perforation: A Case Report, Brielle Corrente Mar 2019

Aortoduodenal Fistula Forms From Primary Aortic Stump Graft In A Two-Time Multi-Visceral Transplant Patient With Presentation Of Gastrointestinal Bleed And Bowel Perforation: A Case Report, Brielle Corrente

Graduate Student Research Symposium

Usually not diagnosed until open laparotomy, aortoduodenalfistulas (ADF) are one of the rarest complications of intestinal transplant surgery. With an incidence rate of only 0.04% at autopsy and only 250 documented cases since the early 1800’s, aortoduodenal fistulas are the most deadly complications of intestinal transplantation with a mortality rate of 100% without surgical intervention. A 39 year old, two-time multi-visceral transplant African American female patient suffered from a primary aortoduodenal fistula formation in a primary modified multi-visceral transplant aortic stump graft site. With emergency open laparotomy repair, revascularization of the secondary multi-visceral transplant was performed, saving the life of …


Assessment Of The Visual Analogue Score In The Evaluation Of The Pruritus Of Cholestasis, Nora Bergasa, E Jones Sep 2017

Assessment Of The Visual Analogue Score In The Evaluation Of The Pruritus Of Cholestasis, Nora Bergasa, E Jones

NYMC Faculty Publications

Background and Aims: A visual analogue score (VAS), based on application of a visual analogue scale, has been widely used to assess pruritus in clinical studies of patients with cholestatic liver disease. A VAS is a numerical score of the severity of the perception of pruritus, and, hence, is inherently subjective. The objective of this study was to assess the reliability of a VAS as an index of pruritus in cholestatic patients. Methods: In 8 patients with chronic pruritus due to primary biliary cholangitis, values for a VAS of pruritus were compared with corresponding measurements of scratching activity, which were …


Evaluation Of Preoperative Anemia And Transfusion Requirements In Adult Liver Transplant Recipients, Parissa M.N. Moghimi, Erika A. Aldag, Rachel Pedersen, Ajay Sahajpal, Jacob N. Clendenon, Vikraman Gunabushanam, Mehraboon S. Irani, David J. Kramer Nov 2016

Evaluation Of Preoperative Anemia And Transfusion Requirements In Adult Liver Transplant Recipients, Parissa M.N. Moghimi, Erika A. Aldag, Rachel Pedersen, Ajay Sahajpal, Jacob N. Clendenon, Vikraman Gunabushanam, Mehraboon S. Irani, David J. Kramer

Journal of Patient-Centered Research and Reviews

Background: Liver transplantation is often associated with massive blood loss due to surgical complexity and the hemostatic abnormalities of end-stage liver disease. Blood transfusions have been associated with increased risk of infection, multiorgan dysfunction, graft loss and mortality.

Purpose: To determine for liver transplantation whether correlation exists between preoperative anemia and transfusion requirements, length of stay or incidence of postoperative infection.

Methods: A retrospective review of liver transplantations from Jan. 1, 2012, to June 30, 2015, was conducted. Packed red blood cell (PRBC), fresh frozen plasma (FFP), platelet and cryoprecipitate units were collected preoperatively, intraoperatively and within the first 48 …


Alcoholic Hepatitis Accelerates Early Hepatobiliary Cancer By Increasing Stemness And Mir-122-Mediated Hif-1alpha Activation, Aditya Ambade, Abhishek Satishchandran, Gyongyi Szabo Aug 2016

Alcoholic Hepatitis Accelerates Early Hepatobiliary Cancer By Increasing Stemness And Mir-122-Mediated Hif-1alpha Activation, Aditya Ambade, Abhishek Satishchandran, Gyongyi Szabo

Gyongyi Szabo

Alcohol-related hepatocellular carcinoma (HCC) develops with advanced alcoholic liver disease and liver fibrosis. Using adult mice, we evaluate the effect of alcoholic steatohepatitis on early hepatobiliary carcinoma after initiation by diethyl-nitrosamine (DEN). Here we show that alcohol-fed DEN-injected mice have higher ALT and liver-to-body weight ratio compared to pair-fed DEN-injected mice. Alcohol feeding results in steatohepatitis indicated by increased pro-inflammatory cytokines and fibrotic genes. MRI and liver histology of alcohol+DEN mice shows hepatobiliary cysts, early hepatic neoplasia and increase in serum alpha-fetoprotein. Proliferation makers (BrdU, cyclin D1, p53) and cancer stem cell markers (CD133 and nanog) are significantly up-regulated in …


Salvage Therapy For Non-Acetaminophen-Induced Acute Liver Failure Includes N-Acetylcysteine, David Robinson Jul 2016

Salvage Therapy For Non-Acetaminophen-Induced Acute Liver Failure Includes N-Acetylcysteine, David Robinson

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009;137(3):856-864. doi: 10.1053/j.gastro.2009.06.006


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 Sep 2015

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 hepatitis …


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 Sep 2015

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 danger …


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 Aug 2015

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, …


Microrna-155 Deficiency Attenuates Liver Steatosis And Fibrosis Without Reducing Inflammation In A Mouse Model Of Steatohepatitis, Timea Csak, Shashi Bala, Dora Lippai, Karen Kodys, Donna Catalano, Arvin Iracheta-Vellve, Gyongyi Szabo Aug 2015

Microrna-155 Deficiency Attenuates Liver Steatosis And Fibrosis Without Reducing Inflammation In A Mouse Model Of Steatohepatitis, Timea Csak, Shashi Bala, Dora Lippai, Karen Kodys, Donna Catalano, Arvin Iracheta-Vellve, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND and AIM: MicroRNAs (miRs) regulate hepatic steatosis, inflammation and fibrosis. Fibrosis is the consequence of chronic tissue damage and inflammation. We hypothesized that deficiency of miR-155, a master regulator of inflammation, attenuates steatohepatitis and fibrosis.

METHODS: Wild type (WT) and miR-155-deficient (KO) mice were fed methionine-choline-deficient (MCD) or -supplemented (MCS) control diet for 5 weeks. Liver injury, inflammation, steatosis and fibrosis were assessed.

RESULTS: MCD diet resulted in steatohepatitis and increased miR-155 expression in total liver, hepatocytes and Kupffer cells. Steatosis and expression of genes involved in fatty acid metabolism were attenuated in miR-155 KO mice after MCD feeding. …


Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo Sep 2014

Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo

Katherine A. Fitzgerald

Emerging evidence suggests that innate immunity drives alcoholic liver disease (ALD) and that the interferon regulatory factor 3 (IRF3),a transcription factor regulating innate immune responses, is indispensable for the development of ALD. Here we report that IRF3 mediates ALD via linking endoplasmic reticulum (ER) stress with apoptotic signaling in hepatocytes. We found that ethanol induced ER stress and triggered the association of IRF3 with the ER adaptor, stimulator of interferon genes (STING), as well as subsequent phosphorylation of IRF3. Activated IRF3 associated with the proapoptotic molecule Bax [B-cell lymphoma 2 (Bcl2)-associated X protein] and contributed to hepatocyte apoptosis. Deficiency of …


Acute Binge Drinking Increases Serum Endotoxin And Bacterial Dna Levels In Healthy Individuals, Shashi Bala, Miguel Marcos, Arijeet Gattu, Donna Catalano, Gyongyi Szabo Sep 2014

Acute Binge Drinking Increases Serum Endotoxin And Bacterial Dna Levels In Healthy Individuals, Shashi Bala, Miguel Marcos, Arijeet Gattu, Donna Catalano, Gyongyi Szabo

Gyongyi Szabo

Binge drinking, the most common form of alcohol consumption, is associated with increased mortality and morbidity; yet, its biological consequences are poorly defined. Previous studies demonstrated that chronic alcohol use results in increased gut permeability and increased serum endotoxin levels that contribute to many of the biological effects of chronic alcohol, including alcoholic liver disease. In this study, we evaluated the effects of acute binge drinking in healthy adults on serum endotoxin levels. We found that acute alcohol binge resulted in a rapid increase in serum endotoxin and 16S rDNA, a marker of bacterial translocation from the gut. Compared to …


Chronic Alcohol-Induced Microrna-155 Contributes To Neuroinflammation In A Tlr4-Dependent Manner In Mice, Dora Lippai, Shashi Bala, Timea Csak, Evelyn A. Kurt-Jones, Gyongyi Szabo Sep 2014

Chronic Alcohol-Induced Microrna-155 Contributes To Neuroinflammation In A Tlr4-Dependent Manner In Mice, Dora Lippai, Shashi Bala, Timea Csak, Evelyn A. Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

INTRODUCTION: Alcohol-induced neuroinflammation is mediated by pro-inflammatory cytokines and chemokines including tumor necrosis factor-alpha (TNFalpha), monocyte chemotactic protein-1 (MCP1) and interleukin-1-beta (IL-1beta). Toll-like receptor-4 (TLR4) pathway induced nuclear factor-kappaB (NF-kappaB) activation is involved in the pathogenesis of alcohol-induced neuroinflammation. Inflammation is a highly regulated process. Recent studies suggest that microRNAs (miRNAs) play crucial role in fine tuning gene expression and miR-155 is a major regulator of inflammation in immune cells after TLR stimulation. AIM: To evaluate the role of miR-155 in the pathogenesis of alcohol-induced neuroinflammation. METHODS: Wild type (WT), miR-155- and TLR4-knockout (KO) mice received 5% ethanol-containing or isocaloric …


High Fat Diet Feeding Results In Gender Specific Steatohepatitis And Inflammasome Activation, Michal Ganz, Timea Csak, Gyongyi Szabo Sep 2014

High Fat Diet Feeding Results In Gender Specific Steatohepatitis And Inflammasome Activation, Michal Ganz, Timea Csak, Gyongyi Szabo

Gyongyi Szabo

AIM: To develop an animal model that encompasses the different facets of non-alcoholic steatohepatitis (NASH), which has been a challenge. METHODS: In this study, we used a high fat diet (HFD) feeding supplemented with fructose and sucrose in the water mimicking the high-fructose corn syrup that is abundant in the diet in the United States. We used C57Bl/6 wild-type mice for short and long-term feedings of 6 and 16 wk respectively, and evaluated the extent of liver damage, steatosis, and inflammasome activation. Our methods included histopathological analysis to assess liver damage and steatosis, which involved H and E and oil-red-o …


Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo Sep 2014

Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo

Gyongyi Szabo

Emerging evidence suggests that innate immunity drives alcoholic liver disease (ALD) and that the interferon regulatory factor 3 (IRF3),a transcription factor regulating innate immune responses, is indispensable for the development of ALD. Here we report that IRF3 mediates ALD via linking endoplasmic reticulum (ER) stress with apoptotic signaling in hepatocytes. We found that ethanol induced ER stress and triggered the association of IRF3 with the ER adaptor, stimulator of interferon genes (STING), as well as subsequent phosphorylation of IRF3. Activated IRF3 associated with the proapoptotic molecule Bax [B-cell lymphoma 2 (Bcl2)-associated X protein] and contributed to hepatocyte apoptosis. Deficiency of …


Circulating Microrna Profiles In Human Patients With Acetaminophen Hepatotoxicity Or Ischemic Hepatitis, Jeanine Ward, Chitra Kanchagar, Isana Veksler-Lublinsky, Rosalind C. Lee, Mitchell R. Mcgill, Hartmut Jaeschke, Steven C. Curry, Victor R. Ambros Aug 2014

Circulating Microrna Profiles In Human Patients With Acetaminophen Hepatotoxicity Or Ischemic Hepatitis, Jeanine Ward, Chitra Kanchagar, Isana Veksler-Lublinsky, Rosalind C. Lee, Mitchell R. Mcgill, Hartmut Jaeschke, Steven C. Curry, Victor R. Ambros

Victor R. Ambros

We have identified, by quantitative real-time PCR, hundreds of miRNAs that are dramatically elevated in the plasma or serum of acetaminophen (APAP) overdose patients. Most of these circulating microRNAs decrease toward normal levels during treatment with N-acetyl cysteine (NAC). We identified a set of 11 miRNAs whose profiles and dynamics in the circulation during NAC treatment can discriminate APAP hepatotoxicity from ischemic hepatitis. The elevation of certain miRNAs can precede the dramatic rise in the standard biomarker, alanine aminotransferase (ALT), and these miRNAs also respond more rapidly than ALT to successful treatment. Our results suggest that miRNAs can serve as …


Hepatocellular Carcinoma In Native South Asian Pakistani Population; Trends, Clinico-Pathological Characteristics & Differences In Viral Marker Negative & Viral-Hepatocellular Carcinoma, Amna Subhan Butt1, Saeed Hamid, Ashfaq Ahmad Wadalawala, Mariam Ghufran, Ammar Asrar Javed, Omer Farooq, Bilal Ahmed, Tanveer Ul Haq, Wasim Jafri Apr 2013

Hepatocellular Carcinoma In Native South Asian Pakistani Population; Trends, Clinico-Pathological Characteristics & Differences In Viral Marker Negative & Viral-Hepatocellular Carcinoma, Amna Subhan Butt1, Saeed Hamid, Ashfaq Ahmad Wadalawala, Mariam Ghufran, Ammar Asrar Javed, Omer Farooq, Bilal Ahmed, Tanveer Ul Haq, Wasim Jafri

Section of Gastroenterology

Background

HCC is the fifth most common cancer globally. Our study was conducted to (1)investigate the trends and clinico-pathological characteristics of Hepatocellular carcinoma among native South Asian patients in Pakistan, (2)to estimate the prevalence as well as the trends of viral marker negative HCC and (3) to compare the clinico-pathological, radiological characteristics, applicability of treatment at diagnosis and prognostic factors among patients with both viral marker negative and viral marker positive-HCC being consulted at Aga Khan University Hospital(AKUH), Karachi, Pakistan.

Method

Patients ≥18 years, already diagnosed to have HCC and visiting AKUH during 1999–2009 were identified using ICD code 1550. …