Gastroenterology Commons^™

Limited Sampling Estimates Of Epigallocatechin Gallate Exposures In Cirrhotic And Noncirrhotic Patients With Hepatitis C After Single Oral Doses Of Green Tea Extract., Dina Halegoua-De Marzio, Walter K. Kraft, Constantine Daskalakis, Xie Ying, Roy L Hawke, Victor J. Navarro

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Epigallocatechin-3-gallate (EGCG) has antiangiogenic, antioxidant, and antifibrotic properties that may have therapeutic potential for the treatment of cirrhosis induced by hepatitis C virus (HCV). However, cirrhosis might affect EGCG disposition and augment its reported dose-dependent hepatotoxic potential.

OBJECTIVE: The safety, tolerability, and disposition of a single oral dose of EGCG in cirrhotic patients with HCV were examined in an exploratory fashion.

METHODS: Eleven patients with hepatitis C and detectable viremia were enrolled. Four had Child-Pugh (CP) class A cirrhosis, 4 had Child-Pugh class B cirrhosis, and 3 were noncirrhotic. After a single oral dose of green tea extract 400 …

The Association Between Acrochorda (Skin Tags), Metabolic Syndrome, And Adenomatous Polyps, Brendan O'Hare, Md, Anastasia Shnitser, Md, Jason Korenblit, Md, Mba, Ali Siddiqui, Md

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND

Acrochorda (skin tags) are benign skin tumors that form primarily at skin creases, generally on the neck, armpit, and groin areas. There have been a small number of published studies in 1980s in patients who were found to have increased number of skin tags and colonic polyps, with a direct correlation described between the two. In addition, metabolic syndrome has been linked to adenomatous polyps, but a link between skin tags and metabolic syndrome has not been established.

Development Of A Competency-Based Transplant Hepatology Fellowship, Steven K. Herrine, Andrew P. Keaveny, Ayman Abdel-Latif Koteish, Richard K. Sterling, John R. Lake

Division of Gastroenterology and Hepatology Faculty Papers

Presented at 63rd annual meeting AASLD, The Liver Meeting, Boston MA, November 9-13, 2012.

Purpose: The Accreditation Council for Graduate Medical Education (ACGME) next accreditation system (NAS) provides incentive for medical educators to understand and implement competency-based medical education (CBME) training and assessment in their programs. Noting decreasing enrollees for the American Board of Internal Medicine (ABIM) Transplant Hepatology (TH) exam, workforce concerns in TH, and questionnaire data from Gastroenterology (GI) fellows and Program Directors (PDs), we developed an ABIM-approved one-year competency-based TH pilot program.

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 …

Plasma Microrna Profiles Distinguish Lethal Injury In Acetaminophen Toxicity: A Research Study, Jeanine Ward, Shashi Bala, Jan Petrasek, Gyongyi Szabo

Gyongyi Szabo

AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed, we screened commercially available murine microRNA libraries (SABiosciences, Qiagen Sciences, MD) to evaluate for unique miRNA profiles between these two dosing parameters. RESULTS: We distinguished numerous, unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and downregulated miRNAs, namely 574-5 p, 466 g, 466 f-3p, 375, 29 c, and 148 a, have …

Sleep Disturbances And Hypnotic Medication Use In Relation To Risk Of Barrett’S Esophagus And Esophageal Adenocarcinoma, Anastasia Shnitser, Md, Abhik Roy, Md, Sidney Cohen, Md, Anthony J. Dimarino, Md

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND

The incidence of esophageal adenocarcinoma (EA) has increased more rapidly than any other cancer (with the exception of malignant melanoma) in the United States over the past 30 years. Gastroesophageal reflux disease (GERD) is the strongest risk factor for the development of Barrett’s esophagus, which in turn leads to the rise of most EA’s. In a large portion of persons with sleep disorders, perhaps as high as 30%, GERD is a major causal or contributing factor. It has been proposed that the use of hypnotics for the treatment of sleep disorders may exacerbate the damaging effects of refluxate on …

Predictive Value Of Alpha-Fetoprotein In The Long-Term Risk Of Developing Hepatocellular Carcinoma In Patients With Hepatitis B Virus Infection--Results From A Clinic-Based Longitudinal Cohort., Hie-Won Hann, Xiaoying Fu, Ronald E. Myers, Richard Hann, Shaogui Wan, Su Hee Kim, Natalie Au, Jinliang Xing, Hushan Yang

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Although serum level of alpha-fetoprotein (AFP) has long been used to complement imaging tests in the screening and diagnosis of hepatocellular carcinoma (HCC), whether it can be used as a predictive marker of long-term risk for developing HCC in patients with hepatitis B virus (HBV) has not been extensively evaluated and thus remains controversial.

METHODS: We retrospectively conducted a clinic-based longitudinal cohort study including 617 Korean American patients with HBV who had been followed for up to 22 years (median follow-up time, 6.2 years) to evaluate the association between baseline serum AFP level and the long-term risk of HCC. …

Frequency Of Poor Quality Of Life And Predictors Of Health Related Quality Of Life In Cirrhosis At A Tertiary Care Hospital Pakistan, Om Parkash, Romaina Iqbal, Fatima Jafri, Iqbal Azam, Wasim Jafri

Section of Gastroenterology

Background

Cirrhosis produces variety of symptoms which eventually lead to a negative impact on Health Related Quality of Life (HRQOL). The general aim of this study was to evaluate the magnitude of poor HRQOL and to assess factors related with HRQOL in patients with CLD in Pakistan.

Findings

This was a cross sectional study conducted in gastroenterology outpatient clinics of Aga Khan University Hospital, Karachi on adult patients with cirrhosis. In this study chronic liver disease questionnaire (CLDQ) was used to assess HRQOL of these patients and CLDQ score was used as an outcome measure to determine factors related with …

Rhoa/Rock Pathway Is The Major Molecular Determinant Of Basal Tone In Intact Human Internal Anal Sphincter, Satish Rattan, Jagmohan Singh

Division of Gastroenterology and Hepatology Faculty Papers

Poster presented at: Digestive Disease Week (DDW) International meeting in San Diego, California.

Background and Aims

Knowledge of molecular control mechanisms underlying the basal tone in the intact human IAS is critical for the pathophysiology and rational therapy for debilitating rectoanal motility disorders.

Effect Of Pooled Human Intravenous Globulin (Ivig) On The Reversal Of Cholinergic Inhibition Of Smooth Muscle By Immunoglobulins (Iggs) From Patients With Scleroderma (Ssc), Jagmohan Singh, Vaibhav Mehendiratta, Sergio A. Jimenez, Sidney Cohen, Anthony J. Dimarino, Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

Poster presented at: Digestive Disease Week (DDW) International meeting in San Diego, California.

Backgrounds and Aims:

The gastrointestinal (GI) tract is the most common internal organ system affected in SSc. We and others have shown before that the SSc immunoglobulins (IgGs) cause selective blockade of muscarinic type-3 cholinergic (M3-R) in the GI tract. Presently, there is no effective treatment for SSc although numerous cytotoxic and immunomodulatory agents have been employed with limited success and are marred with serious side effects. Present studies investigated the reversibility of SScIgGs-caused M3-R blockade by the pooled Intravenous immunoglobulins (IVIG).

Development Of Myogenic Ias Reconstructs From Human Internal Anal Sphincter (Ias) Smooth Muscle Cells (Smcs) With Functional And Molecular Properties Similar To Intact Human Ias, Jagmohan Singh, Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

Poster presented at: Digestive Disease Week (DDW) International meeting in San Diego, California.

Background and Aims:

Rectoanal incontinence is associated with defective Internal Anal Sphincter (IAS). Current therapies are not satisfactory, raising a potential for the replacement of the dysfunctional IAS with the reconstructs. Present studies were performed to develop human IAS smooth muscle reconstructs with functional and molecular attributes similar to the intact human IAS Smooth muscle (SM).

Relative Telomere Length: A Novel Non-Invasive Biomarker For The Risk Of Non-Cirrhotic Hepatocellular Carcinoma In Patients With Chronic Hepatitis B Infection., Xiaoying Fu, Shaogui Wan, Hie-Won Hann, Md, Ronald E Myers, Phd, Richard S Hann, Jennifer Au, Bicui Chen, Jinliang Xing, Hushan Yang

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND AND AIMS: Telomere length has emerged as a promising risk predictor of various cancers including hepatocellular carcinoma (HCC). However, the majority of studies in this area measured telomere length in hepatocytes and one in lymphocytes with conflicting results. Moreover, no studies have been reported on using circulating DNA telomere length as a non-invasive HCC biomarker.

METHODS: We conducted a nested case-control study to determine the relative telomere length (RTL) in serum DNA from 140 hepatitis B virus (HBV)-related HCC cases and 280 frequency-matched cancer-free HBV controls.

RESULTS: Cases had a significantly longer RTL (median, 0.31; range, 0.02-2.31) than controls …

The Use Of Infliximab In Older Inflammatory Bowel Disease Patients, Stephanie M. Moleski, Christina C. Lindenmeyer, Patricia L. Kozuch

Department of Medicine Faculty Papers

Limited data suggest anti-tumor necrosis factor (TNF) antibodies have equal efficacy but higher morbidity and mortality in older compared to younger inflammatory bowel disease (IBD) patients(1).

Balloon-Occluded Retrograde Transvenous Obliteration For The Treatment Of Gastric Varices., Alia S Dadabhai, Jonathan M Fenkel, Daniel B Brown, Loren Laine

Division of Gastroenterology and Hepatology Faculty Papers

Clinical Perspectives in Hepatology aims to engage two experts with opinions supporting differing perspectives on the management of a case. Typically, the case represents an area of debate or evolving practice in clinical hepatology.

The patient presented below gives us the opportunity to discuss balloon-occluded retrograde transvenous obliteration (BRTO) for treatment of gastric varices. Although described since the mid-1990s and accepted as effective therapy, particularly in Japan, BRTO is used sporadically in the United States and Europe. In fact, it is not mentioned in the U.S. (AASLD) or European (EASL/Baveno V) guidelines. Hopefully, increased awareness of and expertise in this …

Patterns Of Acetaminophen Use At A Tertiary Care Center: Exposures Exceeding 4 Grams Daily, Jesse Civan, Victor Navarro, Jeffrey Riggio, Paul Adams, Steven Herrine, Simona Rossi

Jefferson Hospital Staff Papers and Presentations

Unintentional hepatotoxicity due to acetaminophen use at the recommended daily dose of up to four grams daily has increasingly been recognized as a significant problem. The phrase "therapeutic misadventure" has been coined in the literature, in reference to biochemical evidence of hepatocellular injury associated with acetaminophen use at recommended doses. Previous studies have documented a 25% to 40% incidence of two- to three-fold alanie aminotransferase (ALT) elevation, in healty volunteers administered one gram of acetaminophen every six hours.

The recognition of this problem is reflected in part by recent changes in FDA recommendations, including more stringent controls on the amount …

Boerhaave's Syndrome As A First Presentation Of Eosinophilic Esophagitis, Whitney E. Jackson, Vaibhav Mehendiratta, Juan P. Palazzo, Anthony J. Dimarino, Sidney Cohen

Division of Internal Medicine Faculty Papers & Presentations

Purpose: Prior studies have reported esophageal rupture following endoscopy or bolus impaction in eosinophilic esophagitis. The purpose of this study is to examine the frequency and characteristics of spontaneous rupture (Boerhaave's Syndrome) associated with vomiting S-435 AGA Abstracts in eosinophilic esophagitis.

Methods: A retrospective search of inpatient and outpatient records was conducted for the diagnoses "Boerhaave's", "eosinophilic esophagitis", and "esophageal rupture" from January 2001 to January 2011 within the gastroenterology division at an urban tertiary care hospital. For each subject identified, medical records, endoscopy reports, biopsy reports and radiographic studies were reviewed. A faculty member of the Department of Pathology …

Self Expanding Metal Stents (Sems) For Management Of Peri-Pancreatic Fluid Collections (Pfc): A Single Center Experience, Whitney E. Jackson, Jason Korenblit, Vaibhav Mehendiratta, Jason Lewis, Ali A. Siddiqui, Thomas E. Kowalski, David E. Loren

Division of Internal Medicine Faculty Papers & Presentations

Background

Endoscopic management of peri-pancreatic fluid collections (PFC) with or without organizing necrosis has been shown to decrease morbidity and mortality compared to early surgical management. Plastic stents are often used for transmural drainage, although the use of self-expanding metal stents (SEMS) has been reported. Theoretical benefits of SEMS include a large diameter for drainage and facilitation of endoscopic necrosectomy. We report a single-center experience to evaluate the efficacy and safety of SEMS for management of PFC.

Methods

A single-center retrospective review was performed of patients undergoing endoscopic management of PFC using SEMS from January through November 2011. Electronic database …

The Effect On Colon Visualization During Colonoscopy Of The Addition Of Simethicone To Polyethylene Glycol-Electrolyte Solution: A Randomized Single-Blind Study., Rebecca Matro, Keegan Tupchong, Constantine Daskalakis, Victoria Gordon, Leo Katz, David Kastenberg

Division of Gastroenterology and Hepatology Faculty Papers

OBJECTIVES: Colonic bubbles associated with polyethylene glycol-electrolyte solution (PEG-ELS) are common and obscure mucosal visualization. This study aimed to determine whether adding simethicone decreases the incidence of bubbles.

METHODS: Prospective, single-blind, randomized comparison of split dose PEG-ELS vs. PEG-ELS+simethicone (PEG-S) for outpatient colonoscopy. Bubble severity for colonic segments was assessed on withdrawal as A=no/minimal bubbles, B=moderate bubbles/interfere with detecting 5 mm polyp, C=severe bubbles/interfere with detecting 10 mm polyp. Primary end point was Grade B or C bubbles in any colon segment. Secondary end points were cleansing quality, incidence and severity of side effects, and polyp detection.

RESULTS: One hundred …