Hepatology Commons^™

Gene Content, Phage Cycle Regulation Model And Prophage Inactivation Disclosed By Prophage Genomics In The Helicobacter Pylori Genome Project, Filipa F Vale, Richard J Roberts, Ichizo Kobayashi, M Constanza Camargo, Charles S Rabkin, Hpgp Research Network

Faculty, Staff and Students Publications

Prophages can have major clinical implications through their ability to change pathogenic bacterial traits. There is limited understanding of the prophage role in ecological, evolutionary, adaptive processes and pathogenicity of Helicobacter pylori, a widespread bacterium causally associated with gastric cancer. Inferring the exact prophage genomic location and completeness requires complete genomes. The international Helicobacter pylori Genome Project (HpGP) dataset comprises 1011 H. pylori complete clinical genomes enriched with epigenetic data. We thoroughly evaluated the H. pylori prophage genomic content in the HpGP dataset. We investigated population evolutionary dynamics through phylogenetic and pangenome analyses. Additionally, we identified …

The Impact Of Obesity-Associated Glycine Deficiency On The Elimination Of Endogenous And Exogenous Metabolites Via The Glycine Conjugation Pathway, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

BACKGROUND: Glycine is an integral component of the human detoxification system as it reacts with potentially toxic exogenous and endogenously produced compounds and metabolites via the glycine conjugation pathway for urinary excretion. Because individuals with obesity have reduced glycine availability, this detoxification pathway may be compromised. However, it should be restored after bariatric surgery because of increased glycine production.

OBJECTIVE: To examine the impact of obesity-associated glycine deficiency on the glycine conjugation pathway. We hypothesize that the synthesis rates of acylglycines from endogenous and exogenous sources are significantly reduced in individuals with obesity but increase after bariatric surgery.

METHODS: We …

Protein Biomarkers Gdf15 And Fgf21 To Differentiate Mitochondrial Hepatopathies From Other Pediatric Liver Diseases, Johan L K Van Hove, Marisa W Friederich, Dana K Strode, Roxanne A Van Hove, Kristen R Miller, Rohit Sharma, Hardik Shah, Jane Estrella, Linda Gabel, Simon Horslen, Rohit Kohli, Mark A Lovell, Alexander G Miethke, Jean P Molleston, Rene Romero, James E Squires, Estella M Alonso, Stephen L Guthery, Binita M Kamath, Kathleen M Loomes, Philip Rosenthal, Krupa R Mysore, Laurel A Cavallo, Pamela L Valentino, John C Magee, Shikha S Sundaram, Ronald J Sokol, Childhood Liver Disease Research Network (Children)

Faculty, Staff and Students Publications

BACKGROUND: Mitochondrial hepatopathies (MHs) are primary mitochondrial genetic disorders that can present as childhood liver disease. No recognized biomarkers discriminate MH from other childhood liver diseases. The protein biomarkers growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) differentiate mitochondrial myopathies from other myopathies. We evaluated these biomarkers to determine if they discriminate MH from other liver diseases in children.

METHODS: Serum biomarkers were measured in 36 children with MH (17 had a genetic diagnosis); 38 each with biliary atresia, α1-antitrypsin deficiency, and Alagille syndrome; 20 with NASH; and 186 controls.

RESULTS: GDF15 levels compared to controls were …

Genetic Variation Between Small Bowel And Colon-Predominant Crohn's Disease, Halee Patel, R Alan Harris, Justin H Qian, Numan Oezguen, Ashleigh Watson, Reka G Szigeti, Stanley Cho, Wenly Ruan, Savini Britto, Antone Opekun, Geoffrey Preidis, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.

Frailty In End-Stage Liver Disease: Understanding Pathophysiology, Tools For Assessment, And Strategies For Management, Mazen Elsheikh, Ahmed El Sabagh, Islam B Mohamed, Megha Bhongade, Manal M Hassan, Prasun Kumar Jalal

Faculty, Staff and Students Publications

Frailty and sarcopenia are frequently observed in patients with end-stage liver disease. Frailty is a complex condition that arises from deteriorations across various physiological systems, including the musculoskeletal, cardiovascular, and immune systems, resulting in a reduced ability of the body to withstand stressors. This condition is associated with declined resilience and increased vulnerability to negative outcomes, including disability, hospitalization, and mortality. In cirrhotic patients, frailty is influenced by multiple factors, such as hyperammonemia, hormonal imbalance, malnutrition, ascites, hepatic encephalopathy, and alcohol intake. Assessing frailty is crucial in predicting morbidity and mortality in cirrhotic patients. It can aid in making critical …

Effectiveness Of Conservative Management Versus Laparoscopic Cholecystectomy In The Prevention Of Recurrent Symptoms And Complications In Adults With Uncomplicated Symptomatic Gallstone Disease (C-Gall Trial): Pragmatic, Multicentre Randomised Controlled Trial, Irfan Ahmed, Jemma Hudson, Karen Innes, Rodolfo Hernández, Katie Gillies, Rebecca Bruce, Victoria Bell, Alison Avenell, Jane Blazeby, Miriam Brazzelli, Seonaidh Cotton, Bernard Croal, Mark Forrest, Graeme Maclennan, Peter Murchie, Samantha Wileman, Craig Ramsay, C-Gall Study Group

Faculty, Staff and Student Publications

OBJECTIVE: To assess the clinical and cost effectiveness of conservative management compared with laparoscopic cholecystectomy for the prevention of symptoms and complications in adults with uncomplicated symptomatic gallstone disease.

DESIGN: Parallel group, pragmatic randomised, superiority trial.

SETTING: 20 secondary care centres in the UK.

PARTICIPANTS: 434 adults (>18 years) with uncomplicated symptomatic gallstone disease referred to secondary care, assessed for eligibility between August 2016 and November 2019, and randomly assigned (1:1) to receive conservative management or laparoscopic cholecystectomy.

INTERVENTIONS: Conservative management or surgical removal of the gallbladder.

MAIN OUTCOME MEASURES: The primary patient outcome was quality of life, measured …

Characterizing Prostate Cancer Risk Through Multi-Ancestry Genome-Wide Discovery Of 187 Novel Risk Variants, Anqi Wang, Jiayi Shen, Alex A Rodriguez, Edward J Saunders, Fei Chen, Rohini Janivara, Burcu F Darst, Xin Sheng, Yili Xu, Alisha J Chou, Sara Benlloch, Tokhir Dadaev, Mark N Brook, Anna Plym, Ali Sahimi, Thomas J Hoffman, Atushi Takahashi, Koichi Matsuda, Yukihide Momozawa, Masashi Fujita, Triin Laisk, Jéssica Figuerêdo, Kenneth Muir, Shuji Ito, Xiaoxi Liu, Yuji Uchio, Michiaki Kubo, Yoichiro Kamatani, Artitaya Lophatananon, Peggy Wan, Caroline Andrews, Adriana Lori, Parichoy P Choudhury, Johanna Schleutker, Teuvo L J Tammela, Csilla Sipeky, Anssi Auvinen, Graham G Giles, Melissa C Southey, Robert J Macinnis, Cezary Cybulski, Dominika Wokolorczyk, Jan Lubinski, Christopher T Rentsch, Kelly Cho, Benjamin H Mcmahon, David E Neal, Jenny L Donovan, Freddie C Hamdy, Richard M Martin, Borge G Nordestgaard, Sune F Nielsen, Maren Weischer, Stig E Bojesen, Andreas Røder, Hein V Stroomberg, Jyotsna Batra, Suzanne Chambers, Lisa Horvath, Judith A Clements, Wayne Tilly, Gail P Risbridger, Henrik Gronberg, Markus Aly, Robert Szulkin, Martin Eklund, Tobias Nordstrom, Nora Pashayan, Alison M Dunning, Maya Ghoussaini, Ruth C Travis, Tim J Key, Elio Riboli, Jong Y Park, Thomas A Sellers, Hui-Yi Lin, Demetrius Albanes, Stephanie Weinstein, Michael B Cook, Lorelei A Mucci, Edward Giovannucci, Sara Lindstrom, Peter Kraft, David J Hunter, Kathryn L Penney, Constance Turman, Catherine M Tangen, Phyllis J Goodman, Ian M Thompson, Robert J Hamilton, Neil E Fleshner, Antonio Finelli, Marie-Élise Parent, Janet L Stanford, Elaine A Ostrander, Stella Koutros, Laura E Beane Freeman, Meir Stampfer, Alicja Wolk, Niclas Håkansson, Gerald L Andriole, Robert N Hoover, Mitchell J Machiela, Karina Dalsgaard Sørensen, Michael Borre, William J Blot, Wei Zheng, Edward D Yeboah, James E Mensah, Yong-Jie Lu, Hong-Wei Zhang, Ninghan Feng, Xueying Mao, Yudong Wu, Shan-Chao Zhao, Zan Sun, Stephen N Thibodeau, Shannon K Mcdonnell, Daniel J Schaid, Catharine M L West, Gill Barnett, Christiane Maier, Thomas Schnoeller, Manuel Luedeke, Adam S Kibel, Bettina F Drake, Olivier Cussenot, Geraldine Cancel-Tassin, Florence Menegaux, Thérèse Truong, Yves Akoli Koudou, Esther M John, Eli Marie Grindedal, Lovise Maehle, Kay-Tee Khaw, Sue A Ingles, Mariana C Stern, Ana Vega, Antonio Gómez-Caamaño, Laura Fachal, Barry S Rosenstein, Sarah L Kerns, Harry Ostrer, Manuel R Teixeira, Paula Paulo, Andreia Brandão, Stephen Watya, Alexander Lubwama, Jeannette T Bensen, Ebonee N Butler, James L Mohler, Jack A Taylor, Manolis Kogevinas, Trinidad Dierssen-Sotos, Gemma Castaño-Vinyals, Lisa Cannon-Albright, Craig C Teerlink, Chad D Huff, Patrick Pilie, Yao Yu, Ryan J Bohlender, Jian Gu, Sara S Strom, Luc Multigner, Pascal Blanchet, Laurent Brureau, Radka Kaneva, Chavdar Slavov, Vanio Mitev, Robin J Leach, Hermann Brenner, Xuechen Chen, Bernd Holleczek, Ben Schöttker, Eric A Klein, Ann W Hsing, Rick A Kittles, Adam B Murphy, Christopher J Logothetis, Jeri Kim, Susan L Neuhausen, Linda Steele, Yuan Chun Ding, William B Isaacs, Barbara Nemesure, Anselm J M Hennis, John Carpten, Hardev Pandha, Agnieszka Michael, Kim De Ruyck, Gert De Meerleer, Piet Ost, Jianfeng Xu, Azad Razack, Jasmine Lim, Soo-Hwang Teo, Lisa F Newcomb, Daniel W Lin, Jay H Fowke, Christine M Neslund-Dudas, Benjamin A Rybicki, Marija Gamulin, Davor Lessel, Tomislav Kulis, Nawaid Usmani, Aswin Abraham, Sandeep Singhal, Matthew Parliament, Frank Claessens, Steven Joniau, Thomas Van Den Broeck, Manuela Gago-Dominguez, Jose Esteban Castelao, Maria Elena Martinez, Samantha Larkin, Paul A Townsend, Claire Aukim-Hastie, William S Bush, Melinda C Aldrich, Dana C Crawford, Shiv Srivastava, Jennifer Cullen, Gyorgy Petrovics, Graham Casey, Ying Wang, Yao Tettey, Joseph Lachance, Wei Tang, Richard B Biritwum, Andrew A Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Kosj Yamoah, Koveela Govindasami, Anand P Chokkalingam, Jacob M Keaton, Jacklyn N Hellwege, Peter E Clark, Mohamed Jalloh, Serigne M Gueye, Lamine Niang, Olufemi Ogunbiyi, Olayiwola Shittu, Olukemi Amodu, Akindele O Adebiyi, Oseremen I Aisuodionoe-Shadrach, Hafees O Ajibola, Mustapha A Jamda, Olabode P Oluwole, Maxwell Nwegbu, Ben Adusei, Sunny Mante, Afua Darkwa-Abrahams, Halimatou Diop, Susan M Gundell, Monique J Roobol, Guido Jenster, Ron H N Van Schaik, Jennifer J Hu, Maureen Sanderson, Linda Kachuri, Rohit Varma, Roberta Mckean-Cowdin, Mina Torres, Michael H Preuss, Ruth J F Loos, Matthew Zawistowski, Sebastian Zöllner, Zeyun Lu, Stephen K Van Den Eeden, Douglas F Easton, Stefan Ambs, Todd L Edwards, Reedik Mägi, Timothy R Rebbeck, Lars Fritsche, Stephen J Chanock, Sonja I Berndt, Fredrik Wiklund, Hidewaki Nakagawa, John S Witte, J Michael Gaziano, Amy C Justice, Nick Mancuso, Chikashi Terao, Rosalind A Eeles, Zsofia Kote-Jarai, Ravi K Madduri, David V Conti, Christopher A Haiman

Faculty, Staff and Student Publications

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in …

Predictive Algorithm For Hepatic Steatosis Detection Using Elastography Data In The Veterans Affairs Electronic Health Records, Saroja Bangaru, Ram Sundaresh, Anna Lee, Nicole Prause, Frank Hao, Tien S Dong, Monica Tincopa, George Cholankeril, Nicole E Rich, Jenna Kawamoto, Debika Bhattacharya, Steven B Han, Arpan A Patel, Magda Shaheen, Jihane N Benhammou

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) has reached pandemic proportions. Early detection can identify at-risk patients who can be linked to hepatology care. The vibration-controlled transient elastography (VCTE) controlled attenuation parameter (CAP) is biopsy validated to diagnose hepatic steatosis (HS). We aimed to develop a novel clinical predictive algorithm for HS using the CAP score at a Veterans' Affairs hospital.

METHODS: We identified 403 patients in the Greater Los Angeles VA Healthcare System with valid VCTEs during 1/2018-6/2020. Patients with alcohol-associated liver disease, genotype 3 hepatitis C, any malignancies, or liver transplantation were excluded. Linear regression was used …

Incidence And Outcomes Of Acute Kidney Injury Including Hepatorenal Syndrome In Hospitalized Patients With Cirrhosis In The Us, Kavish R Patidar, Justin M Belcher, Kevin R Regner, Shelsea A St Hillien, Douglas A Simonetto, Sumeet K Asrani, Javier A Neyra, Pratima Sharma, Juan Carlos Q Velez, Hani Wadei, Mitra K Nadim, Raymond T Chung, Ritu Seethapathy, Xavier Vela Parada, Tianqi Ouyang, Nneka N Ufere, Jevon E Robinson, Paige Mclean Diaz, Robert M Wilechansky, Eric M Przybyszewski, Thomas N Smith, Arzina Aziz Ali, Eric S Orman, Philipp Schulz, Salaah M Siddiqui, Rehma Shabbir, Lucas J Liu, Augusto Cama-Olivares, Alexander H Flannery, Megan L Baker, Deepthi Gunasekaran, Adeline Aswine, Rafik Issa, Jay Li, Shreya Verma, Dustin Chalmers, Vipin Varghese, Walter Lam, Muner Mohamed, Rosemary Kovacic, Anna Gaddy, Rose Mary Attieh, Pedro Cortes, Sahar Semnani, Lin Wang, Saro Khemichian, Andrew S Allegretti

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis.

METHODS: We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other).

RESULTS: A total of 2,063 patients were included (median age 62 …

A Multisociety Delphi Consensus Statement On New Fatty Liver Disease Nomenclature, Mary E Rinella, Jeffrey V Lazarus, Vlad Ratziu, Sven M Francque, Arun J Sanyal, Fasiha Kanwal, Diana Romero, Manal F Abdelmalek, Quentin M Anstee, Juan Pablo Arab, Marco Arrese, Ramon Bataller, Ulrich Beuers, Jerome Boursier, Elisabetta Bugianesi, Christopher D Byrne, Graciela E Castro Narro, Abhijit Chowdhury, Helena Cortez-Pinto, Donna R Cryer, Kenneth Cusi, Mohamed El-Kassas, Samuel Klein, Wayne Eskridge, Jiangao Fan, Samer Gawrieh, Cynthia D Guy, Stephen A Harrison, Seung Up Kim, Bart G Koot, Marko Korenjak, Kris V Kowdley, Florence Lacaille, Rohit Loomba, Robert Mitchell-Thain, Timothy R Morgan, Elisabeth E Powell, Michael Roden, Manuel Romero-Gómez, Marcelo Silva, Shivaram Prasad Singh, Silvia C Sookoian, C Wendy Spearman, Dina Tiniakos, Luca Valenti, Miriam B Vos, Vincent Wai-Sun Wong, Stavra Xanthakos, Yusuf Yilmaz, Zobair Younossi, Ansley Hobbs, Marcela Villota-Rivas, Philip N Newsome, Nafld Nomenclature Consensus Group

Faculty, Staff and Students Publications

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 …

Therapeutic Implications Of Impaired Nuclear Receptor Function And Dysregulated Metabolism In Wilson’S Disease, Clavia Ruth Wooton-Kee

Faculty, Staff and Students Publications

Copper is an essential trace element that is required for the activity of many enzymes and cellular processes, including energy homeostasis and neurotransmitter biosynthesis; however, excess copper accumulation results in significant cellular toxicity. The liver is the major organ for maintaining copper homeostasis. Inactivating mutations of the copper-transporting P-type ATPase, ATP7B, result in Wilson’s disease, an autosomal recessive disorder that requires life-long medicinal therapy or liver transplantation. Current treatment protocols are limited to either sequestration of copper via chelation or reduction of copper absorption in the gut (zinc therapy). The goal of these strategies is to reduce free copper, redox …

Relationships Among Intragastric Meal Distribution During Gastric Emptying Scintigraphy, Water Consumption During Water Load Satiety Testing, And Symptoms Of Gastroparesis, Henry P Parkman, Laura A Wilson, Paul Silver, Alan H Maurer, Irene Sarosiek, Robert S Bulat, Braden Kuo, Madhusudan Grover, Gianrico Farrugia, Bruno P Chumpitazi, Robert J Shulman, Zubair Malik, Laura A Miriel, James Tonascia, Frank Hamilton, Thomas L Abell, Pankaj J Pasricha, Richard W Mccallum, Kenneth L Koch, Niddk Gastroparesis Clinical Research Consortium

Faculty, Staff and Students Publications

Gastric emptying scintigraphy (GES) measures total gastric retention after a solid meal and can assess intragastric meal distribution (IMD). Water load satiety test (WLST) measures gastric capacity. Both IMD immediately after meal ingestion [ratio of proximal gastric counts after meal ingestion to total gastric counts at time 0 (IMD⁰)] and WLST (volume of water ingested over 5 min) are indirect measures of gastric accommodation. In this study, IMD⁰ and WLST were compared with each other and to symptoms of gastroparesis to gauge their clinical utility for assessing patients with symptoms of gastroparesis. Patients with symptoms of gastroparesis …

Preterm Pigs Fed Donor Human Milk Have Greater Liver Β-Carotene Concentrations Than Pigs Fed Infant Formula, Nancy E Moran, Joshua Wade, Rachel Stroh, Barbara Stoll, Gregory Guthrie, Amy B Hair, Douglas G Burrin

Faculty, Staff and Students Publications

BACKGROUND: Milk carotenoids may support preterm infant health and neurodevelopment. Infants fed human milk often have higher blood and tissue carotenoid concentrations than infants fed carotenoid-containing infant formula (IF). Donor human milk (DHM) is a supplement to mother's own milk, used to support preterm infant nutrition.

OBJECTIVES: We tested whether tissue and plasma β-carotene concentrations would be higher in preterm pigs fed pasteurized DHM versus premature IF.

METHODS: This is a secondary analysis of samples collected from a study of the effects of enteral diet composition on necrotizing enterocolitis incidence. Preterm pigs received partial enteral feeding of either DHM (n …

Sarcopenia Is Associated With Osteopenia And Impaired Quality Of Life In Children With Genetic Intrahepatic Cholestatic Liver Disease, Julia M Boster, Nathan P Goodrich, Cathie Spino, Kathleen M Loomes, Estella M Alonso, Binita M Kamath, Ronald J Sokol, Saul Karpen, Alexander Miethke, Benjamin L Shneider, Jean P Molleston, Rohit Kohli, Simon P Horslen, Philip Rosenthal, Pamela L Valentino, Jeffrey H Teckman, Thomas N Hangartner, Shikha S Sundaram

Faculty, Staff and Students Publications

BACKGROUND: Sarcopenia occurs in pediatric chronic liver disease, although the prevalence and contributing factors in genetic intrahepatic cholestasis are not well-described. The objective of this study was to measure muscle mass in school-aged children with genetic intrahepatic cholestasis and assess relationships between sarcopenia, clinical variables, and outcomes.

METHODS: Estimated skeletal muscle mass (eSMM) was calculated on dual-energy x-ray absorptiometry obtained in a Childhood Liver Disease Research Network study of children with bile acid synthesis disorders(BASD) alpha-1 antitrypsin deficiency (a1ATd), chronic intrahepatic cholestasis (CIC), and Alagille syndrome (ALGS). Relationships between eSMM, liver disease, and transplant-free survival were assessed.

RESULTS: eSMM was …

Paired Liver:Plasma Pfas Concentration Ratios From Adolescents In The Teen-Labs Study And Derivation Of Empirical And Mass Balance Models To Predict And Explain Liver Pfas Accumulationn, Brittney O Baumert, Fabian C Fischer, Flemming Nielsen, Philippe Grandjean, Scott Bartell, Nikos Stratakis, Douglas I Walker, Damaskini Valvi, Rohit Kohli, Thomas Inge, Justin Ryder, Todd Jenkins, Stephanie Sisley, Stavra Xanthakos, Sarah Rock, Michele A La Merrill, David Conti, Rob Mcconnell, Lida Chatzi

Faculty, Staff and Students Publications

Animal studies have pointed at the liver as a hotspot for per- and polyfluoroalkyl substances (PFAS) accumulation and toxicity, however, these findings have not been replicated in human populations. We measured concentrations of seven PFAS in matched liver and plasma samples collected at the time of bariatric surgery from 64 adolescents in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study. Liver:plasma concentrations ratios were perfectly explained (r2 > 0.99) in a multi-linear regression (MLR) model based on toxicokinetic (TK) descriptors consisting of binding to tissue constituents and membrane permeabilities. Of the seven matched plasma and liver PFAS concentrations compared in this …

An Efficient Strategy For Evaluating New Non-Invasive Screening Tests For Colorectal Cancer: The Guiding Principles, Robert S Bresalier, Carlo Senore, Graeme P Young, James Allison, Robert Benamouzig, Sally Benton, Patrick M M Bossuyt, Luis Caro, Beatriz Carvalho, Han-Mo Chiu, Veerle M H Coupé, Willemijn De Klaver, Clasine Maria De Klerk, Evelien Dekker, Sunil Dolwani, Callum G Fraser, William Grady, Lydia Guittet, Samir Gupta, Stephen P Halloran, Ulrike Haug, Geir Hoff, Steven Itzkowitz, Tim Kortlever, Anastasios Koulaouzidis, Uri Ladabaum, Beatrice Lauby-Secretan, Mārcis Leja, Bernard Levin, Theodore Robert Levin, Finlay Macrae, Gerrit A Meijer, Joshua Melson, Colm O'Morain, Susan Parry, Linda Rabeneck, David F Ransohoff, Roque Sáenz, Hiroshi Saito, Silvia Sanduleanu-Dascalescu, Robert E Schoen, Kevin Selby, Harminder Singh, Robert J C Steele, Joseph J Y Sung, Erin Leigh Symonds, Sidney J Winawer, Members Of The World Endoscopy Colorectal Cancer Screening New Test Evaluation Expert Working Group

Faculty, Staff and Student Publications

OBJECTIVE: New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers.

DESIGN: A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles.

RESULTS: Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a …

Guidelines On Cholangioscopy For Indeterminate Biliary Strictures: One Step Closer To Consensus, Fares Ayoub, Mohamed O Othman

Faculty, Staff and Students Publications

No abstract provided.

The Improving Medication Adherence In Adolescents And Young Adults Following Liver Transplantation (Imalt) Multisite Trial: Design And Trial Implementation Considerations, Eyal Shemesh, Sarah Duncan-Park, George Mazariegos, Rachel Annunziato, Ravinder Anand, Miguel Reyes-Mugica, Jeff Mitchell, Benjamin L Shneider

Faculty, Staff and Students Publications

BACKGROUND/AIMS: Medication non-adherence is a leading cause of transplant rejection, organ loss, and death; yet no rigorous controlled study to date has shown compelling clinical benefits from an adherence-improving intervention. Non-adherent patients are less likely to participate in trials, and therefore, most studies enroll a majority of adherent patients who do not stand to benefit from the intervention, as they do not have the condition (non-adherence) under investigation. The improving Medication Adherence in adolescent Liver Transplant recipients trial specifically targets non-adherent patients to investigate whether a remote intervention to improve adherence results in reduced incidence of biopsy-confirmed rejection.

METHODS: Improving …

A Pilot Genome-Wide Association Study Meta-Analysis Of Gastroparesis, Leticia Camargo Tavares, Tenghao Zheng, Madeline Kwicklis, Emily Mitchell, Anita Pandit, Suraj Pullapantula, Cheryl Bernard, Maris Teder-Laving, Francine Z Marques, Tonu Esko, Braden Kuo, Robert J Shulman, Bruno P Chumpitazi, Kenneth L Koch, Irene Sarosiek, Thomas L Abell, Richard W Mccallum, Henry P Parkman, Pankaj J Pasricha, Frank A Hamilton, James Tonascia, Matthew Zawistowski, Gianrico Farrugia, Madhusudan Grover, Mauro D'Amato

Faculty, Staff and Students Publications

BACKGROUND: Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction.

OBJECTIVE: Genetic predisposition may play a role; however, investigation at the genome-wide level has not been performed.

METHODS: We carried out a genome-wide association study (GWAS) meta-analysis on (i) 478 GP patients from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) compared to 9931 population-based controls from the University of Michigan Health and Retirement Study; and (ii) 402 GP cases compared to 48,340 non-gastroparesis controls from the Michigan Genomics Initiative. Associations for 5,811,784 high-quality SNPs were tested on …

Tuberculosis Incidence In Foreign-Born People Residing In European Countries In 2020, Anca Vasiliu, Niklas Köhler, Ekkehardt Altpeter, Tinna Rán Ægisdóttir, Marina Amerali, Wouter Arrazola De Oñate, Ágnes Bakos, Stefania D'Amato, Daniela Maria Cirillo, Reinout Van Crevel, Edita Davidaviciene, Irène Demuth, Jose Domínguez, Raquel Duarte, Gunar Günther, Jean-Paul Guthmann, Sophia Hatzianastasiou, Louise Hedevang Holm, Zaida Herrador, Urška Hribar, Conny Huberty, Elmira Ibraim, Sarah Jackson, Mogens Jensenius, Kamilla Sigridur Josefsdottir, Anders Koch, Maria Korzeniewska-Kosela, Liga Kuksa, Heinke Kunst, Christian Lienhardt, Beatrice Mahler, Mateja Janković Makek, Inge Muylle, Johan Normark, Analita Pace-Asciak, Goranka Petrović, Despo Pieridou, Giulia Russo, Olena Rzhepishevska, Helmut J F Salzer, Marta Sá Marques, Daniela Schmid, Ivan Solovic, Mariya Sukholytka, Petra Svetina, Mariya Tyufekchieva, Tuula Vasankari, Piret Viiklepp, Kersti Villand, Jiri Wallenfels, Stefan Wesolowski, Anna-Maria Mandalakas, Leonardo Martinez, Dominik Zenner, Christoph Lange, Tbnet

Faculty, Staff and Students Publications

Background

European-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.

Aim

We aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening.

Methods

The Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries …

Pediatric Drug-Associated Pancreatitis Reveals Concomitant Risk Factors And Poor Reliability Of Causality Scoring: Report From Insppire, Veronique D Morinville, Sohail Z Husain, Fuchenchu Wang, Gretchen A Cress, Maisam Abu-El-Haija, Ankur Chugh, Elissa Downs, Kate Ellery, Douglas S Fishman, Alvin Jay Freeman, Cheryl E Gariepy, Matthew Giefer, Tanja Gonska, Quin Liu, Asim Maqbool, Jacob Mark, Brian Arthur Mcferron, Megha Mehta, Jaimie D Nathan, Ken Ng, Chee Y Ooi, Emily Perito, Wenly Ruan, Sarah Jane Schwarzenberg, Zachary M Sellers, Jose Serrano, David M Troendle, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark Lowe, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

OBJECTIVES: Drug-associated acute pancreatitis (DAP) studies typically focus on single acute pancreatitis (AP) cases. We aimed to analyze the (1) characteristics, (2) co-risk factors, and (3) reliability of the Naranjo scoring system for DAP using INSPPIRE-2 (the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2) cohort study of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children.

METHODS: Data were obtained from ARP group with ≥1 episode of DAP and CP group with medication exposure ± DAP. Physicians could report multiple risk factors. Pancreatitis associated with Medication (Med) (ARP+CP) was compared to Non-Medication cases, and ARP-Med …

Updates On The Immune Cell Basis Of Hepatic Ischemia-Reperfusion Injury, Mi Jeong Heo, Ji Ho Suh, Kyle L Poulsen, Cynthia Ju, Kang Ho Kim

Faculty, Staff and Student Publications

Liver ischemia-reperfusion injury (IRI) is the main cause of organ dysfunction and failure after liver surgeries including organ transplantation. The mechanism of liver IRI is complex and numerous signals are involved but cellular metabolic disturbances, oxidative stress, and inflammation are considered the major contributors to liver IRI. In addition, the activation of inflammatory signals exacerbates liver IRI by recruiting macrophages, dendritic cells, and neutrophils, and activating NK cells, NKT cells, and cytotoxic T cells. Technological advances enable us to understand the role of specific immune cells during liver IRI. Accordingly, therapeutic strategies to prevent or treat liver IRI have been …

Age Differences In Core Symptoms And Symptom Relationships In Patients With Irritable Bowel Syndrome: A Network Analysis, Pei-Lin Yang, Kendra J Kamp, Robert L Burr, Hsin-Yi Jean Tang, Adrian Dobra, Robert J Shulman, Margaret M Heitkemper

Faculty, Staff and Students Publications

INTRODUCTION: Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, characterized by symptoms of abdominal pain and changes in bowel habits. It often co-occurs with extraintestinal somatic and psychological symptoms. However, the nature of the interrelationships among these symptoms is unclear. Although previous studies have noted age differences in IBS prevalence and specific symptom severity, it remains unknown whether specific symptoms and symptom relationships may differ by age.

METHODS: Symptom data were collected in 355 adults with IBS (mean age 41.4 years, 86.2% female). Network analysis was used to examine the interrelationships among 28 symptoms and to identify …

Safety And Efficacy Of Immune Checkpoint Inhibitors In Patients With Cancer And Viral Hepatitis: The Md Anderson Cancer Center Experience, Mirella Nardo, Bulent Yilmaz, Blessie Elizabeth Nelson, Harrys A Torres, Lan Sun Wang, Bruno Palma Granwehr, Juhee Song, Hanna R F Dalla Pria, Van A Trinh, Isabella C Glitza Oliva, Sapna P Patel, Nizar M Tannir, Ahmed Omar Kaseb, Mehmet Altan, Sunyoung S Lee, Ethan Miller, Hao Zhang, Bettzy A Stephen, Aung Naing

Faculty, Staff and Student Publications

Background: Despite the clinical benefit of immune checkpoint inhibitors (ICIs), patients with a viral hepatitis have been excluded from clinical trials because of safety concerns. The purpose of this study was to determine the incidence rate of adverse events (AEs) in patients with viral hepatitis who received ICIs for cancer treatment.

Materials and methods: We conducted a retrospective study in patients with cancer and concurrent hepatitis B or C, who had undergone treatment with ICI at MD Anderson Cancer Center from January 1, 2010 to December 31, 2019.

Results: Of the 1076 patients screened, we identified 33 with concurrent hepatitis. …

Nonalcoholic Steatohepatitis-Related Hepatocellular Carcinoma: Pathogenesis And Treatment, Josep M Llovet, Catherine E Willoughby, Amit G Singal, Tim F Greten, Mathias Heikenwälder, Hashem B El-Serag, Richard S Finn, Scott L Friedman

Faculty, Staff and Students Publications

Nonalcoholic fatty liver disease (NAFLD), including its more severe manifestation, nonalcoholic steatohepatitis (NASH), has a global prevalence of 20-25% and is a major public health problem. Its incidence is increasing in parallel to the rise in obesity, diabetes and metabolic syndrome. Progression from NASH to NASH-related hepatocellular carcinoma (HCC) (~2% of cases per year) is influenced by many factors, including the tissue and immune microenvironment, germline mutations in PNPLA3, and the microbiome. NASH-HCC has unique molecular and immune traits compared with other aetiologies of HCC and is equally prevalent in men and women. Comorbidities associated with NASH, such as obesity …

Monocyte-Derived Macrophages Orchestrate Multiple Cell-Type Interactions To Repair Necrotic Liver Lesions In Disease Models, Dechun Feng, Xiaogang Xiang, Yukun Guan, Adrien Guillot, Hongkun Lu, Chingwen Chang, Yong He, Hua Wang, Hongna Pan, Cynthia Ju, Sean P Colgan, Frank Tacke, Xin Wei Wang, George Kunos, Bin Gao

Faculty, Staff and Student Publications

The liver can fully regenerate after partial resection, and its underlying mechanisms have been extensively studied. The liver can also rapidly regenerate after injury, with most studies focusing on hepatocyte proliferation; however, how hepatic necrotic lesions during acute or chronic liver diseases are eliminated and repaired remains obscure. Here, we demonstrate that monocyte-derived macrophages (MoMFs) were rapidly recruited to and encapsulated necrotic areas during immune-mediated liver injury and that this feature was essential in repairing necrotic lesions. At the early stage of injury, infiltrating MoMFs activated the Jagged1/notch homolog protein 2 (JAG1/NOTCH2) axis to induce cell death-resistant SRY-box transcription factor …

Reduction In Racial And Ethnic Disparity In Survival Following Liver Transplant For Hepatocellular Carcinoma In The Direct-Acting Antiviral Era, Anjiya Shaikh, Karthik Goli, Tzu-Hao Lee, Nicole E Rich, Jihane N Benhammou, Stephanie Keeling, Donghee Kim, Aijaz Ahmed, John Goss, Abbas Rana, Amit G Singal, Fasiha Kanwal, George Cholankeril

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Black patients with hepatocellular cancer (HCC), often attributed to hepatitis C virus (HCV) infection, have suboptimal survival following liver transplant (LT). We evaluated the impact of direct-acting antiviral (DAA) availability on racial and ethnic disparities in wait list burden post-LT survival for candidates with HCC.

METHODS: Using the United Network for Organ Sharing registry, we identified patients with HCC who were listed and/or underwent LT from 2009 to 2020. Based on date of LT, patients were categorized into 2 era-based cohorts: the pre-DAA era (LT between 2009 and 2011) and DAA era (LT between 2015 and 2017, …

Seladelpar Efficacy And Safety At 3 Months In Patients With Primary Biliary Cholangitis: Enhance, A Phase 3, Randomized, Placebo-Controlled Study, Gideon M Hirschfield, Mitchell L Shiffman, Aliya Gulamhusein, Kris V Kowdley, John M Vierling, Cynthia Levy, Andreas E Kremer, Ehud Zigmond, Pietro Andreone, Stuart C Gordon, Christopher L Bowlus, Eric J Lawitz, Richard J Aspinall, Daniel S Pratt, Karina Raikhelson, Maria S Gonzalez-Huezo, Michael A Heneghan, Sook-Hyang Jeong, Alma L Ladrón De Guevara, Marlyn J Mayo, George N Dalekos, Joost P H Drenth, Ewa Janczewska, Barbara A Leggett, Frederik Nevens, Victor Vargas, Eli Zuckerman, Christophe Corpechot, Eduardo Fassio, Holger Hinrichsen, Pietro Invernizzi, Palak J Trivedi, Lisa Forman, David E J Jones, Stephen D Ryder, Mark G Swain, Alexandra Steinberg, Pol F Boudes, Yun-Jung Choi, Charles A Mcwherter, Enhance Study Group

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA).

APPROACH AND RESULTS: Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events.

CONCLUSIONS: Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver …

Many Pediatric Patients With Gastroparesis Do Not Receive Dietary Education, Debra Eseonu, Deepa Dongarwar, Hamisu Salihu, Bruno P Chumpitazi, Robert J Shulman

Faculty, Staff and Students Publications

BACKGROUND: Gastroparesis is delayed gastric emptying in the absence of obstruction; dietary modifications are first-line treatment. However, we do not know the factors related to provision of dietary recommendations.

METHODS: We sought to determine how often pediatric patients with gastroparesis receive dietary education (from a gastroenterology provider vs dietitian), the recommendations given, and factors related to these outcomes. We performed a retrospective chart review of children 2- to 18-years-old managed by pediatric gastroenterology providers at our institution. Patient demographics and clinical data, dietary advice given (if any), and dietitian consultation (if any), practice location, and prokinetic use were captured. An …

Histone Demethylase Kdm5d Upregulation Drives Sex Differences In Colon Cancer, Jiexi Li, Zhengdao Lan, Wenting Liao, James W Horner, Xueping Xu, Jielin Liu, Yohei Yoshihama, Shan Jiang, Hong Seok Shim, Max Slotnik, Kyle A Labella, Chang-Jiun Wu, Kenneth Dunner, Wen-Hao Hsu, Rumi Lee, Isha Khanduri, Christopher Terranova, Kadir Akdemir, Deepavali Chakravarti, Xiaoying Shang, Denise J Spring, Y Alan Wang, Ronald A Depinho

Faculty, Staff and Student Publications

Sex exerts a profound impact on cancer incidence, spectrum and outcomes, yet the molecular and genetic bases of such sex differences are ill-defined and presumptively ascribed to X-chromosome genes and sex hormones1. Such sex differences are particularly prominent in colorectal cancer (CRC) in which men experience higher metastases and mortality. A murine CRC model, engineered with an inducible transgene encoding oncogenic mutant KRASG12D and conditional null alleles of Apc and Trp53 tumour suppressors (designated iKAP)2, revealed higher metastases and worse outcomes specifically in males with oncogenic mutant KRAS (KRAS*) CRC. Integrated cross-species molecular and transcriptomic analyses identified Y-chromosome gene histone …