Hepatology Commons^™

Serum Biomarkers Correlated With Liver Stiffness Assessed In A Multicenter Study Of Pediatric Cholestatic Liver Disease, Daniel H Leung, Sridevi Devaraj, Nathan P Goodrich, Xinpu Chen, Deepthi Rajapakshe, Wen Ye, Victor Andreev, Charles G Minard, Danielle Guffey, Jean P Molleston, Lee M Bass, Saul J Karpen, Binita M Kamath, Kasper S Wang, Shikha S Sundaram, Philip Rosenthal, Patrick Mckiernan, Kathleen M Loomes, M Kyle Jensen, Simon P Horslen, Jorge A Bezerra, John C Magee, Robert M Merion, Ronald J Sokol, Benjamin L Shneider, Estella Alonso, Lee Bass, Susan Kelly, Mary Riordan, Hector Melin-Aldana, Jorge Bezerra, Kevin Bove, James Heubi, Alexander Miethke, Greg Tiao, Julie Denlinger, Erin Chapman, Ronald Sokol, Amy Feldman, Cara Mack, Michael Narkewicz, Frederick Suchy, Shikha S Sundaram, Johan Van Hove, Benigno Garcia, Mikaela Kauma, Kendra Kocher, Matthew Steinbeiss, Mark Lovell, Kathleen M Loomes, David Piccoli, Elizabeth Rand, Pierre Russo, Nancy Spinner, Jessi Erlichman, Samantha Stalford, Dina Pakstis, Sakya King, Robert Squires, Rakesh Sindhi, Veena Venkat, Kathy Bukauskas, Patrick Mckiernan, Lori Haberstroh, James Squires, Philip Rosenthal, Laura Bull, Joanna Curry, Camille Langlois, Grace Kim, Jeffery Teckman, Vikki Kociela, Rosemary Nagy, Shraddha Patel, Jacqueline Cerkoski, Jean P Molleston, Molly Bozic, Girish Subbarao, Ann Klipsch, Cindy Sawyers, Oscar Cummings, Simon P Horslen, Karen Murray, Evelyn Hsu, Kara Cooper, Melissa Young, Laura Finn, Binita M Kamath, Vicky Ng, Claudia Quammie, Juan Putra, Deepika Sharma, Aishwarya Parmar, Stephen Guthery, Kyle Jensen, Ann Rutherford, Amy Lowichik, Linda Book, Rebecka Meyers, Tyler Hall, Kasper S Wang, Sonia Michail, Danny Thomas, Catherine Goodhue, Rohit Kohli, Larry Wang, Nisreen Soufi, Daniel Thomas, Saul Karpen, Nitika Gupta, Rene Romero, Miriam B Vos, Rita Tory, John-Paul Berauer, Carlos Abramowsky, Jeanette Mcfall, Benjamin L Shneider, Sanjiv Harpavat, Paula Hertel, Daniel Leung, Mary Tessier, Deborah Schady, Laurel Cavallo, Diego Olvera, Christina Banks, Cynthia Tsai, Richard Thompson, Edward Doo, Jay Hoofnagle, Averell Sherker, Rebecca Torrance, Sherry Hall, John Magee, Robert Merion, Cathie Spino, Wen Ye

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.

APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM …

Spatial Molecular And Cellular Determinants Of Stat3 Activation In Liver Fibrosis Progression In Non-Alcoholic Fatty Liver Disease, Jingjing Jiao, Jessica I Sanchez, Omar A Saldarriaga, Luisa M Solis, David J Tweardy, Dipen M Maru, Heather L Stevenson, Laura Beretta

Faculty, Staff and Student Publications

BACKGROUND & AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), is increasing. Individuals with NASH often develop liver fibrosis and advanced liver fibrosis is the main determinant of mortality in individuals with NASH. We and others have reported that STAT3 contributes to liver fibrosis and hepatocellular carcinoma in mice.

METHODS: Here, we explored whether STAT3 activation in hepatocyte and non-hepatocyte areas, measured by phospho-STAT3 (pSTAT3), is associated with liver fibrosis progression in 133 patients with NAFLD. We further characterized the molecular and cellular determinants of STAT3 activation by integrating spatial distribution and …

Eosinophils Protect Against Acetaminophen-Induced Liver Injury Through Cyclooxygenase-Mediated Il-4/Il-13 Production, Long Xu, Yang Yang, Jiali Jiang, Yankai Wen, Jong-Min Jeong, Christoph Emontzpohl, Constance L Atkins, Kangho Kim, Elizabeth A Jacobsen, Hua Wang, Cynthia Ju

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: A better understanding of the underlying mechanism of acetaminophen (APAP)-induced liver injury (AILI) remains an important endeavor to develop therapeutic approaches. Eosinophils have been detected in liver biopsies of patients with APAP overdose. We recently demonstrated a profound protective role of eosinophils against AILI; however, the molecular mechanism had not been elucidated.

APPROACH AND RESULTS: In agreement with our previous data from experiments using genetic deletion of eosinophils, we found that depletion of eosinophils in wild-type (WT) mice by an anti-IL-15 antibody resulted in exacerbated AILI. Moreover, adoptive transfer of eosinophils significantly reduced liver injury and mortality …

Renal Cell Carcinoma Presenting With Upper Gastrointestinal Bleeding: A Case Report, James Mega, Rene Roberts, Mohamed M Shahin, Ahmed Kamel Abdel Aal

Faculty, Staff and Student Publications

Renal cell carcinoma (RCC) is increasing in incidence as more cross sectional imaging is performed with approximately 20%-30% of cases presenting with metastasis at the time of diagnosis. Small bowel metastatic disease is rare, with RCC to the small bowel being exceptionally rare. We present a case report of metastatic RCC that initially presented as upper gastrointestinal bleeding at time of diagnosis. We also provide a brief discussion of small bowel metastatic RCC disease and literature review.

A Method Using Longitudinal Laboratory Data To Predict Future Intestinal Complication In Patients With Crohn's Disease, James Irwin, Anton Lord, Emma Ferguson, Lisa A Simms, Katherine Hanigan, Carlos A Montoya, Graham Radford-Smith

Faculty, Staff and Student Publications

Background

Stenosis, fistulization, and perforation of the bowel are severe outcomes which can occur in patients with Crohn’s disease. Accurate prediction of these events may enable clinicians to alter treatment strategies and avoid these outcomes.

Aims

To study the correlation between longitudinal laboratory testing and subsequent intestinal complications in patients with Crohn’s disease.

Methods

An observational cohort of patients with Crohn’s disease at a single center were analyzed between 01/01/1994 and 06/30/2016. A complication was defined as the development of an intestinal fistula, stenosis, or perforation. Exploratory analysis using Cox regression was performed to select the best statistical method to …

Regulation Of Skeletal Muscle Protein Synthesis In The Preterm Pig By Intermittent Leucine Pulses During Continuous Parenteral Feeding, Marko Rudar, Agus Suryawan, Hanh V Nguyen, Shaji K Chacko, Caitlin Vonderohe, Barbara Stoll, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

BACKGROUND: Extrauterine growth restriction is a common complication of preterm birth. Leucine (Leu) is an agonist for the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling pathway that regulates translation initiation and protein synthesis in skeletal muscle. Previously, we showed that intermittent intravenous pulses of Leu to neonatal pigs born at term receiving continuous enteral nutrition increases muscle protein synthesis and lean mass accretion. Our objective was to determine the impact of intermittent intravenous pulses of Leu on muscle protein anabolism in preterm neonatal pigs administered continuous parenteral nutrition.

METHODS: Following preterm delivery (on day 105 of 115 gestation), …

Effect Of Liquid And Solid Test Meals On Symptoms And Gastric Myoelectrical Activity In Patients With Gastroparesis And Functional Dyspepsia, Kenneth L Koch, Mark Van Natta, Henry P Parkman, Madhusudan Grover, Thomas L Abell, Richard W Mccallum, Hossam A Shaltout, Irene Sarosiek, Gianrico Farrugia, Robert J Shulman, James Tonascia, Laura Miriel, Frank Hamilton, Pankaj J Pasricha, Gastroparesis Clinical Research Consortium

Faculty, Staff and Students Publications

BACKGROUND: Patients with gastroparesis (GP) and functional dyspepsia (FD) have similar symptoms, but the pathophysiology of postprandial symptoms remains uncertain.

AIMS: To compare symptoms and gastric myoelectrical activity (GMA) after liquid and solid test meals in patients with GP and FD.

METHODS: Patients enrolled in the Gastroparesis Clinical Research Consortium Registry were studied. Clinical characteristics were measured with standard questionnaires. GP was determined by 4-h solid-phase gastric scintigraphy. GMA was measured using electrogastrography before and after ingestion of a water load or nutrient bar on separate days. Symptoms were measured on visual analog scales. GMA responses to the water load …

Lnc-Uc147 Is Associated With Disease Stage Of Liver, Gastric, And Renal Cancer, Ana Carolina Rodrigues, Erika Pereira Zambalde, Daniel De Lima Bellan, Edvaldo Da Silva Trindade, Enilze Maria De Souza Fonseca Ribeiro, George Calin, Daniela Fiori Gradia, Jaqueline Carvalho De Oliveira

Faculty, Staff and Student Publications

Lnc-uc.147, a long non-coding RNA derived from a transcribed ultraconserved region (T-UCR), was previously evidenced in breast cancer. However, the role of this region in other tumor types was not previously investigated. The present study aimed to investigate lnc-uc.147 in different types of cancer, as well as to suggest lnc-uc.147 functional and regulation aspects. From solid tumor datasets analysis of The Cancer Genome Atlas (TCGA), deregulated lnc-uc.147 expression was associated with the histologic grade of hepatocellular carcinoma, and with the tumor stage of clear cell renal and gastric adenocarcinoma. Considering the epidemiologic relevance of liver cancer, silencing lnc-uc.147 reduced the …

Is It Time To Re-Think Fast? A Systematic Review And Meta-Analysis Of Contrast-Enhanced Ultrasound (Ceus) And Conventional Ultrasound For Initial Assessment Of Abdominal Trauma, Bayu Sutarjono, Matthew Kessel, Dorian Alexander, Ekjot Grewal

Faculty, Staff and Student Publications

BACKGROUND: The Focused Assessment with Sonography for Trauma (FAST) examination using conventional ultrasound has limited utility for detecting solid organ injury. Therefore, this systematic review and meta-analysis compares the performance of contrast-enhanced ultrasound (CEUS) to conventional ultrasound when used as the initial assessment for abdominal trauma prior to computed tomography (CT) imaging.

METHODS: A systematic literature search of major databases was conducted of human studies investigating the diagnostic accuracy of conventional ultrasound and CEUS occurring prior to CT imaging for abdominal trauma. The study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. The quality of studies …

Supplementing Glycine And N-Acetylcysteine (Glynac) In Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, And Aging Hallmarks: A Randomized Clinical Trial, Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, Rajagopal V Sekhar

Faculty, Staff and Students Publications

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four …

The Axillary View Typically Does Not Contribute To Decision Making In Care For Proximal Humeral Fractures, Alfadl A Abdulfattah, Hanan A Jawkhab, Altaf A Alhazmi, Nada A Alfaifi, Maryam A Sultan, Rajaa A Alnami, Nada Y Kenani, Shorooq A Hamzi, Shahd M Abu Sharha, Ibrahim M Dighriri

Faculty, Staff and Student Publications

Background: Helicobacter pylori (H. pylori) is a severe infection responsible for upper gastrointestinal symptoms (UGISs). Several causes of H. pylori infection include food ingestion and person-to-person transmission. Many lifestyle variables can affect the occurrence of UGISs such as coffee consumption and smoking.

Objective: To assess the association between smoking and coffee consumption and the occurrence of UGISs in patients with active H. pylori infection in Jazan city in Saudi Arabia.

Methodology: A descriptive cross-sectional research design was used to conduct the study between July 2022 and August 2022 in Jazan, southern Saudi Arabia. Male and female Saudis or …

In Vitro And In Vivo Phototoxicity On Gastric Mucosa Induced By Methylene Blue, Hui Yeong Oh, Hyun Ho Choi, Eui Jin Kim, Ji Hye Choi, Sung Sook Choi, Hae Kyung Lee, Hyung-Keun Kim, Sang Woo Kim, Won Sang H Park, Hiun Suk Chae

Faculty, Staff and Student Publications

BACKGROUND: Methylene blue (MB) is used endoscopically to demarcate tumors and as a photosensitizer in photodynamic therapy (PDT). However, there are few in vivo studies about its toxicity in healthy stomach tissue. We performed sequential in vitro and in vivo analyses of MB-induced phototoxicity.

METHODS: We performed in vitro experiments using the AGS human gastric cancer cell line treated with light-emitting diode (LED) irradiation (3.6 J/cm

RESULTS: In vitro, increased concentrations of MB led to higher TUNEL scores. However, cell viability was significantly lower after MB plus LED irradiation than after treatment with MB alone (P < 0.001). In vivo, the TUNEL score was highest immediately after treatment with 0.1% or 0.5% MB plus light irradiation, and the score was significantly higher in the LED illumination plus MB group than in the control group (P < 0.05). The elevated TUNEL score was maintained for 3 days in the MB plus light irradiation group but returned to normal levels on day 10.

CONCLUSIONS: : Endoscopic light …

Comparison Of Two Lipid Emulsions On The Incidence Of Parenteral Nutrition Associated Cholestasis In Neonates, Joy Greenberg, Mamta Naik, John Chapman, Allison Davidson, Essam Imseis

Faculty, Staff and Student Publications

OBJECTIVE: Lipid emulsion contributes to parenteral nutrition associated cholestasis (PNAC). For decades, soybean oil-based intravenous lipid emulsion (SO-ILE) was the predominant product. Recently, a multicomponent lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil and fish oil (SMOF-ILE) has been used off-label in neonatal care. This study evaluates the incidence of PNAC in neonates who received SMOF-ILE or SO-ILE.

METHODS: This was a retrospective review of neonates who received SMOF-ILE or SO-ILE for at least 14 days. Patients receiving SMOF-ILE were matched based on gestational age (GA) and birth weight to a historical cohort receiving SO-ILE. The primary outcomes were …

Multi-Task Learning For Post-Transplant Cause Of Death Analysis: A Case Study On Liver Transplant, Sirui Ding, Qiaoyu Tan, Chia-Yuan Chang, Na Zou, Kai Zhang, Nathan R Hoot, Xiaoqian Jiang, Xia Hu

Faculty, Staff and Student Publications

Organ transplant is the essential treatment method for some end-stage diseases, such as liver failure. Analyzing the post-transplant cause of death (CoD) after organ transplant provides a powerful tool for clinical decision making, including personalized treatment and organ allocation. However, traditional methods like Model for End-stage Liver Disease (MELD) score and conventional machine learning (ML) methods are limited in CoD analysis due to two major data and model-related challenges. To address this, we propose a novel framework called CoD-MTL leveraging multi-task learning to model the semantic relationships between various CoD prediction tasks jointly. Specifically, we develop a novel tree distillation …

Interlink Between The Gut Microbiota And Inflammation In The Context Of Oxidative Stress In Alzheimer’S Disease Progression, Tushar K Das, Bhanu P Ganesh

Faculty, Staff and Student Publications

The microbiota-gut-brain axis is an important pathway of communication and may dynamically contribute to Alzheimer's disease (AD) pathogenesis. Pathological commensal gut microbiota alterations, termed as dysbiosis, can influence intestinal permeability and break the blood-brain barrier which may trigger AD pathogenesis via redox signaling, neuronal, immune, and metabolic pathways. Dysbiosis increases the oxidative stress. Oxidants affect the innate immune system through recognizing microbial-derived pathogens by Toll-like receptors and initiating the inflammatory process. Most of the gut microbiome research work highlights the relationship between the gut microbiota and AD, but the contributory connection between precise bacteria and brain dysfunction in AD pathology …

Impact Of The Covid Pandemic On Mental Health And Training Opportunities Of Public Health Residents From 4 European Countries: A Cross-Sectional Study, Giovanna Failla, Marta Caminiti, José Chen-Xu, Giuseppina Lo Moro, Nausicaa Berselli, Madalena Cabral Ferreira, Filipa Malcata, David Peyre-Costa, Roberto Croci, Giorgia Soldà, Angelo Capodici, Caterina Morcavallo, Francesco Traglia, Fabrizio Cedrone, Ilaria Storti, Alfonso Alonso Jaquete, Martina Antinozzi, Anca Vasiliu

Faculty, Staff and Students Publications

OBJECTIVES: There is little evidence on the impact of the COVID-19 pandemic on Public Health Residents' (PHR) mental health (MH). This study aims at assessing prevalence and risk factors for depression, anxiety and stress in European PHR during the COVID-19 pandemic.

METHODS: Between March and April 2021, an online survey was administered to PHR from France, Italy, Portugal and Spain. The survey assessed COVID-19 related changes in working conditions, training opportunities and evaluated MH outcomes using the Depression Anxiety Stress Scales-21. Multivariable logistic regressions were applied to identify risk factors.

RESULTS: Among the 443 respondents, many showed symptoms of depression …

Long-Term Outcomes And Trends In Liver Transplantation For Hereditary Hemochromatosis In The United States, Peter Lymberopoulos, Sameer Prakash, Anjiya Shaikh, Anshul Bhatnagar, Anthony K Allam, Karthik Goli, John A Goss, Fasiha Kanwal, Abbas Rana, Kris V Kowdley, Prasun Jalal, George Cholankeril

Faculty, Staff and Students Publications

There have been conflicting data regarding liver transplantation (LT) outcomes for hereditary hemochromatosis (HH), with no recent data on LT outcomes in patients with HH in the past decade. Using the United Network for Organ Sharing registry, we evaluated waitlist and post-LT survival in all adult patients listed for HH without concomitant liver disease from 2003 to 2019. Post-LT survival for HH was compared with a propensity-matched (recipient and donor factors) cohort of recipients with chronic liver disease (CLD). From 2003 to 2019, 862 patients with HH were listed for LT, of which 55.6% ( n = 479) patients underwent …

Chronic Liver Disease-Related Mortality In Diabetes Before And During The Covid-19 In The United States, Donghee Kim, Omar Alshuwaykh, Brittany B Dennis, George Cholankeril, Joshua W Knowles, Aijaz Ahmed

Faculty, Staff and Students Publications

BACKGROUND: Global pandemic of COVID-19 represents an unprecedented challenge. COVID-19 has predominantly targeted vulnerable populations with pre-existing chronic medical diseases, such as diabetes and chronic liver disease.

AIMS: We estimated chronic liver disease-related mortality trends among individuals with diabetes before and during the COVID-19 pandemic.

METHODS: Utilizing the US national mortality database and Census, we determined the quarterly age-standardized chronic liver disease-related mortality and quarterly percentage change (QPC) among individuals with diabetes.

RESULTS: The quarterly age-standardized mortality for chronic liver disease and/or cirrhosis among individuals with diabetes remained stable before the COVID-19 pandemic and sharply increased during the COIVD-19 pandemic …

How Widespread And Convenient H Pylori Susceptibility Testing Will Result In Pharmacological Opportunities, Theodore Rokkas, David Y Graham

Faculty, Staff and Students Publications

Introduction:

Until recently antimicrobial therapy for Helicobacter pylori infections was almost universally empirical and based on a combination of expert opinion and local effectiveness. However, the average cure rates rarely achieved more than 80%. The new requirement that all therapeutic regimens reliably achieve high cure rates, the introduction of potassium competitive acid blockers and the availability of susceptibility testing many pharmacological opportunities particularly since all current therapies will require optimization. The ability to rapidly and inexpensively obtain H. pylori susceptibility data using stool samples makes obtaining susceptibility data practical and allows using susceptibility-based therapy routinely for both treatment naïve patient …

Patient Characteristics And Telehealth Visits In A Hepatology Clinic, Maria E. Walters

DNP Projects

BACKGROUND: In an attempt to decrease significant no-show rates amongst telehealth patients in a Hepatology outpatient clinic, a clinic-specific intervention was executed, which was efficient in decreasing no-show rates, however could not continue to be financially supported.

PURPOSE: The purpose of this study was to evaluate correlations between demographic data and social determinants of health with patients who showed and did not show for their telehealth appointments, with an overall goal of determining if there is a need for targeted support for telehealth appointments to decrease no-show rates.

METHODS: Electronic health records of telehealth patients were reviewed in an …