Gastroenterology Commons^™

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

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 …

Fmt Placed By Colonoscopy: Systematic Review And Meta-Analysis, Nadia Huq, Veena Kumaravel, Aboud Affi, Maharaj Singh

Aurora Gastroenterology Faculty

Background: Fecal transplants are successful in the treatment of recurrent or refractory Clostridium difficile infections (CDI), but there is no consensus on the best method of instillation. Studies have shown greater success with lower gastrointestinal tract placement, but technical aspects of placement are not validated.

Purpose: This review aims to identify common traits and procedural techniques of successful fecal microbiota transplant (FMT) therapy via colonoscopy.

Methods: An electronic search was conducted using OVID Medline and PubMed for articles published from January 2010 to January 2016. The primary outcome of interest was cure by FMT placed via colonoscopy.

Results: Of the …

The Clinical, Endoscopic And Histological Spectrum Of The Solitary Rectal Ulcer Syndrome: A Single-Center Experience Of 116 Cases, Shahab Abid, Ali Khawaja, Salima Ahmed Bhimani, Zubair Ahmad, Saeed Hamid, Wasim Jafri

Zubair Ahmad

Background Solitary rectal ulcer syndrome (SRUS) is an uncommon although benign defecation disorder. The aim of this study was to evaluate the variable endoscopic manifestations of SRUS and its association with other diseases. Methods All the patients diagnosed with SRUS histologically from January 1990 to February 2011 at The Aga Khan University, Karachi were included in the study. The medical records were reviewed retrospectively to evaluate the clinical spectrum of the patients along with the endoscopic and histological findings. Results A total of 116 patients were evaluated. The mean age was 37.4 ± 16.6 (range: 13–80) years, 61 (53%) of …

Gastric Juice For The Diagnosis Of H Pylori Infection In Patients On Proton Pump Inhibitors, Javed Yakoob, Shahid Rasool, Z Abbas, Wasim Jafri, Shahab Abid, Muhammad Islam, Zubair Ahmad

Zubair Ahmad

Aim:To determine the efficacy of gastric juice polymerase chain reaction (PCR) for the detection of H pylori infection in comparison with histology and gastric antral biopsy PCR in Patients on a proton pump inhibitor (PPI). Methods: Eighty-five consecutive Patients with dyspeptic symptoms were enrolled. Gastric biopsies for histology, PCR and gastric juice were collected at endoscopy for PCR of the H pylori urease C gene (ure C). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive and negative likelihood ratio for PCR of gastric juice for the H pylori ure C gene was compared to histology and …

Cytokine Changes In Colonic Mucosa Associated With Blastocystis Spp. Subtypes 1 And 3 In Diarrhoea-Predominant Irritable Bowel Syndrome, Javed Yakoob, Zaigham Abbas, Muhammad Waqas Usman, Aisha Sultana, Muhammad Islam, Safia Awan, Zubair Ahmad, Saeed Hamid, Wasim Jafri

Zubair Ahmad

We determined cytokines (e.g. interleukin-8, 10, 12 and TNF-α) expression by peripheral blood mononuclear cells (PBMCs) and in rectal mucosa in diarrhoea-predominant irritable bowel syndrome (D-IBS) with Blastocystis spp. Eighty patients with D-IBS and Blastocystis spp. infection were classified as 'cases' and 80 with D-IBS without Blastocystis spp. infection were classified as 'control'. Cases were subdivided into D-IBS and Blastocystis sp. defined type 1 (subtype-specific primer SB83) and type 3 (SB227). Stool microscopy and culture were performed. Rectal biopsies were obtained for histology and cytokines by real-time PCR for mRNA expression of cytokines. PBMCs IL-8 was similar in different groups …

Low Rate Of Recurrence Of Helicobacter Pylori Infection In Spite Of High Clarithromycin Resistance In Pakistan, Javed Yakoob, Shahab Abid, Wasim Jafri, Zaigham Abbas, Khalid Mumtaz, Saeed Hamid, Rashida Ahmed

Rashida Ahmed

Background The aim was to investigate the reinfection rate of H. pylori during a follow-up period of 12 months in adults who had undergone eradication therapy. Methods One hundred-twenty patients; 116 with gastritis, 3 with duodenal ulcer and 1 gastric ulcer, were studied. Their mean age was 41 ± 13 years (range 18–77) and male: female ratio of 2:1. H. pylori were cultured and antibiotic sensitivity was determined by Epsilometer test (E-test) for clarithromycin (CLR) and amoxicillin (AMX). Primers of urease C gene of H. pylori and Sau-3 and Hha I restriction enzymes were used for polymerase chain reaction-restriction fragment …

Vitamin D Status In Pediatric Irritable Bowel Syndrome, Benjamin U. Nwosu, Louise Maranda, Ninfa Candela

Benjamin U. Nwosu

IMPORTANCE: Irritable bowel syndrome (IBS) is associated with significant morbidity in children and adolescents, and the therapeutic efficacy of available treatment options is limited. The role of vitamin D supplementation in pediatric IBS is unclear as the vitamin D status of pediatric patients with IBS is unknown. Equally, the relationship of vitamin D status with psychosomatic symptoms in children and adolescents is unclear. AIM: To characterize the vitamin D status of pediatric patients with IBS using a case-control study design. HYPOTHESIS: Serum 25-hydroxyvitamin D [25(OH)D] concentration will be similar between patients with IBS and controls. SUBJECTS AND METHODS: A retrospective …

Trefoil Factor 2 (Tff2) Deficiency In Murine Digestive Tract Influences The Immune System, M. Baus- Loncar, J. Schmid, El-Nasir Lalani, I. Rosewell, R. A. Goodlad, H. G.W. Stamp, N. Blin, T. Kayademir

El Nasir Lalani

Background & Aims:

The gastrointestinal trefoil factor family (TFF1, TFF2, TFF3) peptides are considered to play an important role in maintaining the integrity of the mucosa. The physiological role of TFF2 in the protection of the GI tract was investigated in TFF2 deficiency.

Methods:

TFF2-/- mice were generated and differential expression of various genes was assessed by using a mouse expression microarray, quantitative real time PCR, Northern blots or immunohistochemistry.

Results:

On an mRNA level we found 128 differentially expressed genes. We observed modulation of a number of crucial genes involved in innate and adaptive immunity in the TFF2-/- mice. …

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 …

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 …

Increased Risk For Vitamin D Deficiency In Obese Children With Both Celiac Disease And Type 1 Diabetes, Nithya Setty-Shah, Louise S. Maranda, Benjamin U. Nwosu

Benjamin U. Nwosu

Background. It is unknown whether the coexistence of type 1 diabetes (T1D) and celiac disease (CD) increases the risk for vitamin D deficiency.

Aims. To determine the vitamin D status and the risk for vitamin D deficiency in prepubertal children with both T1D and CD compared to controls, TID, and CD.

Subjects and Methods. Characteristics of 62 prepubertal children of age 2–13 y with either CD + T1D (� = 22, 9.9 ± 3.1 y), CD only (� = 18, 8.9 ± 3.3 y), or T1D only (� = 22, 10.1 ± 2.8 y) were compared to 49 controls of …

Does Helicobacter Pylori Protect Against Eosinophilic Esophagitis In Children?, Yoram Elitsur Md, Baraa Alabd Alrazzak, Deborah L. Preston, Yulia Demetieva

Deborah L Preston

Does Helicobacter Pylori Protect Against Eosinophilic Esophagitis In Children?, Yoram Elitsur Md, Baraa Alabd Alrazzak, Deborah L. Preston, Yulia Demetieva

Yoram Elitsur

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

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

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

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

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 …

Upper Endoscopy In Children: Do Symptoms Predict Positive Findings?

Deborah L Preston

No abstract provided.

Outcomes Of Peginterferon Alfa-2a And Ribavirin Combination Therapy In A Resident-Initiated, Multidisciplinary, Hepatitis C Clinic, Nicole M. Agostino Do, Erini Vasiliadis Do, K Nadeem Ahmed Md, Suzanne J. Templer Do, Edward R. Norris Md, Fapa, Fapm, Charles M. Brooks Md, Eric J. Gertner Md, Mph, Joseph L. Yozviak Do, Facp

Edward R Norris MD, FAPA, FAPM

No abstract provided.

Outcomes Of Peginterferon Alfa-2a And Ribavirin Combination Therapy In A Resident-Initiated, Multidisciplinary, Hepatitis C Clinic, Nicole M. Agostino Do, Erini Vasiliadis Do, K Nadeem Ahmed Md, Suzanne J. Templer Do, Edward R. Norris Md, Fapa, Fapm, Charles M. Brooks Md, Eric J. Gertner Md, Mph, Joseph L. Yozviak Do, Facp

Joseph L Yozviak DO, FACP

No abstract provided.

Microrna Signature In Alcoholic Liver Disease, Shashi Bala, Gyongyi Szabo

Gyongyi Szabo

Alcoholic liver disease (ALD) is a major global health problem. Chronic alcohol use results in inflammation and fatty liver, and in some cases, it leads to fibrosis and cirrhosis or hepatocellular carcinoma. Increased proinflammatory cytokines, particularly TNF alpha, play a central role in the pathogenesis of ALD. TNF alpha is tightly regulated at transcriptional and posttranscriptional levels. Recently, microRNAs (miRNAs) have been shown to modulate gene functions. The role of miRNAs in ALD is getting attention, and recent studies suggest that alcohol modulates miRNAs. Recently, we showed that alcohol induces miR-155 expression both in vitro (RAW 264.7 macrophage) and in …

Human Monoclonal Antibody Hcv1 Effectively Prevents And Treats Hcv Infection In Chimpanzees, Trevor J. Morin, Teresa J. Broering, Brett A. Leav, Barbara M. Blair, Kirk J. Rowley, Elisabeth N. Boucher, Yang Wang, Peter S. Cheslock, Michael Knauber, David B. Olsen, Steve W. Ludmerer, Gyongyi Szabo, Robert W. Finberg, Robert H. Purcell, Robert E. Lanford, Donna M. Ambrosino, Deborah C. Molrine, Gregory J. Babcock

Gyongyi Szabo

Hepatitis C virus (HCV) infection is a leading cause of liver transplantation and there is an urgent need to develop therapies to reduce rates of HCV infection of transplanted livers. Approved therapeutics for HCV are poorly tolerated and are of limited efficacy in this patient population. Human monoclonal antibody HCV1 recognizes a highly-conserved linear epitope of the HCV E2 envelope glycoprotein (amino acids 412-423) and neutralizes a broad range of HCV genotypes. In a chimpanzee model, a single dose of 250 mg/kg HCV1 delivered 30 minutes prior to infusion with genotype 1a H77 HCV provided complete protection from HCV infection, …

Il-1 Receptor Antagonist Ameliorates Inflammasome-Dependent Alcoholic Steatohepatitis In Mice, Jan Petrasek, Shashi Bala, Timea Csak, Dora Lippai, Karen Kodys, Victoria Menashy, Matthew Barrieau, So-Yun Min, Evelyn A. Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

Alcoholic liver disease (ALD) is characterized by steatosis and upregulation of proinflammatory cytokines, including IL-1beta. IL-1beta, type I IL-1 receptor (IL-1R1), and IL-1 receptor antagonist (IL-1Ra) are all important regulators of the IL-1 signaling complex, which plays a role in inflammation. Furthermore, IL-1beta maturation is dependent on caspase-1 (Casp-1). Using IL-1Ra-treated mice as well as 3 mouse models deficient in regulators of IL-1beta activation (Casp-1 and ASC) or signaling (IL-1R1), we found that IL-1beta signaling is required for the development of alcohol-induced liver steatosis, inflammation, and injury. Increased IL-1beta was due to upregulation of Casp-1 activity and inflammasome activation. The …

Lipopolysaccharide Induces And Activates The Nalp3 Inflammasome In The Liver, Michal Ganz, Timea Csak, Bharath D. Nath, Gyongyi Szabo

Gyongyi Szabo

AIM: To examine the activation of the Nalp3 inflammasome and its downstream targets following lipopolysaccharide (LPS)-induced stimulation in the liver. METHODS: Six-to-eight-week-old C57BL/6 chow fed mice were injected intraperitoneally with 0.5 mug/g bodyweight LPS and sacrificed 2, 4, 6, 18 or 24 h later. LPS-induced liver damage was confirmed by a biochemical assay to detect alanine aminotransferase (ALT) levels. To determine if LPS stimulation in the liver led to activation of the inflammasome, real-time quantitative polymerase chain reaction was used to evaluate the mRNA expression of components of the Nalp3 inflammasome. Enzyme-linked immunosorbent assays were used to determine the protein …

Increased Microrna-155 Expression In The Serum And Peripheral Monocytes In Chronic Hcv Infection, Shashi Bala, Yaphet Tilahun, Odette Taha, Hawau Alao, Karen Kodys, Donna Catalano, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Hepatitis C Virus (HCV), a single stranded RNA virus, affects millions of people worldwide and leads to chronic infection characterized by chronic inflammation in the liver and in peripheral immune cells. Chronic liver inflammation leads to progressive liver damage. MicroRNAs (miRNA) regulate inflammation (miR-155, -146a and -125b) as well as hepatocyte function (miR-122). METHODS: Here we hypothesized that microRNAs are dysregulated in chronic HCV infection. We examined miRNAs in the circulation and in peripheral monocytes of patients with chronic HCV infection to evaluate if specific miRNA expression correlated with HCV infection. RESULTS: We found that monocytes from chronic HCV …

Serum Microrna-122 And Mir-155 As Biomarkers Of Liver Injury And Inflammation In Models Of Acute And Chronic Liver Disease, Shashi Bala, Jan Petrasek, Shiv Mundkur, Donna Catalano, Jeanine Ward, Ivan Levin, Hawau Alao, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Background: MicroRNAs (miRs) are small non-coding molecules that regulate gene expression. MiRs expression levels change not only in diseased tissues but also in circulation. Further, miRs are stable in frozen samples that make them attractive for biomarker discovery. Recent reports suggest altered expression of circulating miRNAs in various diseases. MiR-122 is highly abundant in hepatocytes where it regulates different metabolic pathways while miR-155 is a central regulator of inflammation. The aim of this study was to evaluate circulating miRNAs as potential markers of hepatocyte damage and inflammation in liver diseases. Methods: Serum/plasma and liver samples were collected from C57/BL6 mice …

Increased Oxidative Capacity Of Circulating Polymorphonuclear Neutrophils (Pmns) In Non-Diabetic Nash Patients, Timea Csak, Karen Kodys, Angela Dolganiuc, Dora Lippai, Michal Ganz, Christopher Marshall, Gyongyi Szabo

Gyongyi Szabo

Background: Inflammation and oxidative stress are key factors in the pathogenesis of non-alcoholic steatohepatitis (NASH). Polymorphonuclear neutrophils are capable to produce significant amounts of reactive oxygen species (ROS) via the NADPH oxidase complex. Increased hepatic neutrophil infiltration has been described in steatohepatitis. We aimed to investigate the in vitro ROS generation by neutrophils of NASH patients and the hepatic NADPH oxidase activity in murine steatohepatitis. Material and methods: PMNs were isolated from peripheral blood of NASH patients (n=16) and healthy controls (n=16). In vitro ROS production was measured by luminol chemiluminescence after phorbol myristate acetate (PMA) or opsonized zymosan stimulation. …

Caspase-1-Dependent, Il-1ss-Mediated Alcoholic Steatohepatitis Is Ameliorated By Il-1 Receptor Antagonist Treatment In Mice, Jan Petrasek, Shashi Bala, Dora Lippai, Karen Kodys, Victoria Menashy, Matthew Barrieau, Evelyn A. Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

Alcoholic liver disease (ALD) is characterized by steatosis and upregulation of pro-inflammatory cytokines, including interleukin (IL)-1β. IL-1β, Type-I IL-1 receptor (IL1R1) and IL-1 receptor antagonist (IL-1Ra) are all part of the IL-1 superfamily that play a role in inflammation. IL-1β maturation is dependent on Caspase-1. Using wild-type (WT), Caspase-1-, IL-1R1- and IL-1Ra deficient mice fed with Lieber-DeCarli alcohol or control diet, we have identified that signaling mediated by the active IL-1β was required for development of alcohol-induced steatosis, inflammation and injury. Increased IL-1β was due to upregulation of Caspase-1 activity and inflammatory activation. The pathogenic role of IL-1 signaling in …