Hepatology Commons^™

Understanding The Role Of Palliative Care Within Routine Care Of Advanced Liver Disease, Simone A. Jarrett, Edward Bley, Richard S. Kalman

Einstein Health Papers

Purpose of Review

This paper aims to investigate the crucial role of palliative care in the management of chronic liver disease (CLD) and cirrhosis. Faced with a global surge in liver-related morbidity and mortality, our goal is to understand the impact of early engagement with palliative care specialists on symptom management, quality of life, and the overall trajectory of advanced liver disease.

Recent Findings

While strides have been made in preventing and treating specific etiologies of CLD, such as viral infections, the escalating rates of alcohol use and obesity present new challenges for physicians. Despite advancements, liver transplantation unfortunately remains …

Advancing Virtual At-Home Care For Community Health Center Patients Using Patient Self-Care Tools, Technology, And Education [Letter], Cheryl Modica, Joy H. Lewis, Curtis Bay

SOMA Faculty Publications

Abstract

Introduction

Health centers are community-based, patient directed primary care providers that offer accessible, high-quality primary care within medically underserved communities. Screening for cancer and managing complex chronic conditions such as diabetes, hypertension, obesity, and depression are vital services for the vulnerable populations seen by community health centers. Delivering care for complex chronic conditions and preventive services using virtual models that integrate self-care tools and technology is an important approach to increasing access for hard-to-reach patients served by health centers.

Objective

This study aimed to explore the use of a virtual care model, applied using a systems approach and patient-driven …

Evolving Concepts In Helicobacter Pylori Management, Steven F Moss, Shailja C Shah, Mimi C Tan, Hashem B El-Serag

Faculty, Staff and Students Publications

Helicobacter pylori is the most common chronic bacterial infection worldwide and the most significant risk factor for gastric cancer, which remains a leading cause of cancer-related death globally. H pylori and gastric cancer continue to disproportionately impact racial and ethnic minority and immigrant groups in the United States. The approach to H pylori case-finding thus far has relied on opportunistic testing based on symptoms or high-risk indicators, such as racial or ethnic background and family history. However, this approach misses a substantial proportion of individuals infected with H pylori who remain at risk for gastric cancer because most infections remain …

Pulsatile Leucine Administration During Continuous Enteral Feeding Enhances Skeletal Muscle Mechanistic Target Of Rapamycin Complex 1 Signaling And Protein Synthesis In A Preterm Piglet Model, 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: Continuous feeding does not elicit an optimal anabolic response in skeletal muscle but is required for some preterm infants. We reported previously that intermittent intravenous pulses of leucine (Leu; 800 μmol Leu·kg–1·h–1 every 4 h) to continuously fed pigs born at term promoted mechanistic target of rapamycin complex 1 (mTORC1) activation and protein synthesis in skeletal muscle.

OBJECTIVES: The aim was to determine the extent to which intravenous Leu pulses activate mTORC1 and enhance protein synthesis in the skeletal muscle of continuously fed pigs born preterm.

METHODS: Pigs delivered 10 d preterm was advanced to full oral feeding >4 …

What's Going Well: A Qualitative Analysis Of Positive Patient And Family Feedback In The Context Of The Diagnostic Process, Stephen K Liu, Fabienne Bourgeois, Joe Dong, Kendall Harcourt, Elizabeth Lowe, Liz Salmi, Eric J Thomas, Natalie Riblet, Sigall K Bell

Faculty, Staff and Student Publications

OBJECTIVES: Accurate and timely diagnosis relies on close collaboration between patients/families and clinicians. Just as patients have unique insights into diagnostic breakdowns, positive patient feedback may also generate broader perspectives on what constitutes a "good" diagnostic process (DxP).

METHODS: We evaluated patient/family feedback on "what's going well" as part of an online pre-visit survey designed to engage patients/families in the DxP. Patients/families living with chronic conditions with visits in three urban pediatric subspecialty clinics (site 1) and one rural adult primary care clinic (site 2) were invited to complete the survey between December 2020 and March 2022. We adapted the …

Circulating Immune Signatures Across Clinical Stages Of Chronic Pancreatitis: A Pilot Study, Rasmus Hagn-Meincke, Phil A Hart, Dana K Andersen, Santhi S Vege, Evan L Fogel, Jose Serrano, Melena D Bellin, Mark D Topazian, Darwin L Conwell, Liang Li, Stephen K Van Den Eeden, Asbjørn M Drewes, Stephen J Pandol, Chris E Forsmark, William E Fisher, Dhiraj Yadav, Søren S Olesen, Walter G Park, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Objective: This pilot study seeks to identify serum immune signatures across clinical stages of patients with chronic pancreatitis (CP).

Methods: We performed a cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies-study. CP subjects were categorised into three clinical stages based on the presence/absence of metabolic complications: (1) CP with no diabetes and exocrine pancreatic dysfunction (EPD), (2) CP with either diabetes or EPD, and (3) CP with diabetes and EPD. Blinded samples were analysed using an 80-plex Luminex assay of cytokines/chemokines/adhesion molecules. Group and pairwise comparisons were performed to …

Circadian Dysfunction Induces Nafld-Related Human Liver Cancer In A Mouse Model, Jennifer Padilla, Noha M Osman, Beatrice Bissig-Choisat, Sandra L Grimm, Xuan Qin, Angela M Major, Li Yang, Dolores Lopez-Terrada, Cristian Coarfa, Feng Li, Karl-Dimiter Bissig, David D Moore, Loning Fu

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Chronic circadian dysfunction increases the risk of non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC), but the underlying mechanisms and direct relevance to human HCC have not been established. In this study, we aimed to determine whether chronic circadian dysregulation can drive NAFLD-related carcinogenesis from human hepatocytes and human HCC progression.

METHODS: Chronic jet lag of mice with humanized livers induces spontaneous NAFLD-related HCCs from human hepatocytes. The clinical relevance of this model was analysed by biomarker, pathological/histological, genetic, RNA sequencing, metabolomic, and integrated bioinformatic analyses.

RESULTS: Circadian dysfunction induces glucose intolerance, NAFLD-associated human HCCs, and human …

Adverse Metabolic Phenotypes In Parenterally Fed Neonatal Pigs Do Not Persist Into Adolescence, Sarah K Elefson, Barbara Stoll, Teresa A Davis, Marta L Fiorotto, Samer W El-Kadi, Kenneth Genovese, Thomas Thymann, Per T Sangild, Douglas G Burrin

Faculty, Staff and Students Publications

BACKGROUND: Nutrition during fetal and neonatal life is an important determinant for the risk of adult-onset diseases, especially type 2 diabetes and obesity.

OBJECTIVES: We aimed to determine whether total parenteral nutrition (TPN) compared with enteral formula feeding [enteral nutrition (EN)] in term piglets during the first 2 wk after birth would increase the long-term (5-mo) development of metabolic syndrome phenotypes with adverse glucose homeostasis, fatty liver disease, and obesity.

METHODS: Neonatal female pigs were administered TPN (n = 12) or fed enterally with a liquid enteral milk-replacer formula (EN, n = 12) for 14 d. After transitioning TPN pigs …

Circulating Microrna Expression And Nonalcoholic Fatty Liver Disease In Adolescents With Severe Obesity, Yi-Jie Li, Brittney O Baumert, Nikos Stratakis, Jesse A Goodrich, Hao-Tian Wu, Jing-Xuan He, Yin-Qi Zhao, Max T Aung, Hong-Xu Wang, Sandrah P Eckel, Douglas I Walker, Damaskini Valvi, Michele A La Merrill, Justin R Ryder, Thomas H Inge, Todd Jenkins, Stephanie Sisley, Rohit Kohli, Stavra A Xanthakos, Andrea A Baccarelli, Rob Mcconnell, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.

AIM: To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.

METHODS: This …

Long-Term Open-Label Vebicorvir For Chronic Hbv Infection: Safety And Off-Treatment Responses, Man-Fung Yuen, Scott Fung, Xiaoli Ma, Tuan Nguyen, Tarek Hassanein, Hie-Won Hann, Magdy Elkhashab, Ronald Nahass, James Park, Ira Jacobson, Walid Ayoub, Steven-Huy Han, Edward Gane, Katie Zomorodi, Ran Yan, Julie Ma, Steven Knox, Luisa Stamm, Maurizio Bonacini, Frank Weilert, Alnoor Ramji, Michael Bennett, Natarajan Ravendhran, Sing Chan, Douglas Dieterich, Paul Yien Kwo, Eugene Schiff, Ho Bae, Jacob Lalezari, Kosh Agarwal, Mark Sulkowski

Department of Medicine Faculty Papers

BACKGROUND & AIMS: The investigational first-generation core inhibitor vebicorvir (VBR) demonstrated safety and antiviral activity over 24 weeks in two phase IIa studies in patients with chronic HBV infection. In this long-term extension study, patients received open-label VBR with nucleos(t)ide reverse transcriptase inhibitors (NrtIs).

METHODS: Patients in this study (NCT03780543) previously received VBR + NrtI or placebo + NrtI in parent studies 201 (NCT03576066) or 202 (NCT03577171). After receiving VBR + NrtI for ≥52 weeks, stopping criteria (based on the treatment history and hepatitis B e antigen status in the parent studies) were applied, and patients either discontinued both VBR …

Impact Of Genetic And Non-Genetic Factors On Phenotypic Diversity In Nbas-Associated Disease, Nicole Hammann, Dominic Lenz, Ivo Baric, Ellen Crushell, Carlo Dionisi Vici, Felix Distelmaier, Francois Feillet, Peter Freisinger, Maja Hempel, Anna L. Khoreva, Martin W. Laass, Yves Lacassie, Elke Lainka, Catherine Larson-Nath, Zhongdie Li, Patryk Lipiński, Eberhard Lurz, André Mégarbané, Susana Nobre, Giorgia Olivieri, Bianca Peters, Paolo Prontera, Lea D. Schlieben, Christine M. Seroogy, Cristina Sobacchi, Shigeru Suzuki, Christel Tran, Jerry Vockley

School of Medicine Faculty Publications

Biallelic pathogenic variants in neuroblastoma-amplified sequence (NBAS) cause a pleiotropic multisystem disorder. Three clinical subgroups have been defined correlating with the localisation of pathogenic variants in the NBAS gene; variants affecting the C-terminal region of NBAS result in SOPH syndrome (short stature, optic atrophy, Pelger-Huët anomaly), variants affecting the Sec 39 domain are associated with infantile liver failure syndrome type 2 (ILFS2) and variants affecting the ß-propeller domain give rise to a combined phenotype. However, there is still unexplained phenotypic diversity across the three subgroups, challenging the current concept of genotype-phenotype correlations in NBAS-associated disease. Therefore, besides examining the genetic …

Autoimmune Hepatitis: An Unusual Presentation., Ahmed Ali Aziz, Muhammad Ali Aziz, Deep Mehta, Muhammad Humayoun Rashid

Journal of Community Hospital Internal Medicine Perspectives

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that occurs in a bimodal age distribution in the second and fifth-sixth decade of life. The disease is more prevalent in females and presents with variable clinical manifestations ranging from being asymptomatic to acute liver failure. AIH is often overlooked and not worked up in elderly patients who present with liver failure. This can lead to increased morbidity and mortality in elderly patients. AIH should be considered as a differential diagnosis in patients who present with elevated transaminases regardless of age or gender as early recognition and treatment leads to improved …

Preclinical Repurposing Of Sitagliptin As A Drug Candidate For Colorectal Cancer By Targeting Cd24/Ctnnb1/Sox4-Centered Signaling Hub, Jing-Wen Shih, Alexander T H Wu, Ntlotlang Mokgautsi, Po-Li Wei, Yan-Jiun Huang

Faculty, Staff and Student Publications

Despite significant advances in treatment modalities, colorectal cancer (CRC) remains a poorly understood and highly lethal malignancy worldwide. Cancer stem cells (CSCs) and the tumor microenvironment (TME) have been shown to play critical roles in initiating and promoting CRC progression, metastasis, and treatment resistance. Therefore, a better understanding of the underlying mechanisms contributing to the generation and maintenance of CSCs is crucial to developing CSC-specific therapeutics and improving the current standard of care for CRC patients. To this end, we used a bioinformatics approach to identify increased CD24/SOX4 expression in CRC samples associated with poor prognosis. We also …

A Transformer-Based Deep Learning Approach For Fairly Predicting Post-Liver Transplant Risk Factors, Can Li, Xiaoqian Jiang, Kai Zhang

Faculty, Staff and Student Publications

Liver transplantation is a life-saving procedure for patients with end-stage liver disease. There are two main challenges in liver transplant: finding the best matching patient for a donor and ensuring transplant equity among different subpopulations. The current MELD scoring system evaluates a patient's mortality risk if not receiving an organ within 90 days. However, the donor-patient matching should also consider post-transplant risk factors, such as cardiovascular disease, chronic rejection, etc., which are all common complications after transplant. Accurate prediction of these risk scores remains a significant challenge. In this study, we used predictive models to solve the above challenges. Specifically, …

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.

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 …

Recent Trends In The Incidence Of Gastric Cancer In The United States, Kyle S Liu, Syed Ahsan Raza, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Gastric cancer (GC) incidence rates overall in the United States have declined over recent decades and are predicted to continue declining. However, there have been mixed recent findings regarding the potential stabilization of rates and potential divergent trends by age group. We used the most recent cancer data for the United States and examined trends in GC between 1992 and 2019, overall and in important subgroups of the population.

METHODS: Age-adjusted GC incidence rates and trends in adults 20 years or older were calculated using data from the Surveillance, Epidemiology, and End Results (SEER) 12 program. Secular trends were …

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 …

Balancing Honest Assessment And Compassion For Learners Experiencing Burnout: A Workshop And Feedback Tool For Clinical Teachers, Gal Barak, Dana Foradori, H Barrett Fromme, Linessa Zuniga, Andrea Dean

Faculty, Staff and Students Publications

INTRODUCTION: Burnout in medical trainees challenges their work effectiveness and impedes their ability to learn. Teachers in the clinical learning environment (CLE) are well situated to identify burnout and are often responsible for learner assessment.

METHODS: We developed a workshop to improve clinical teachers' identification and understanding of learner burnout while empowering them to provide constructive feedback and support. Building on best-practice feedback techniques and utilizing the Maslach Burnout Inventory (MBI) as a framework, we designed the GetINBurnOUT method to provide feedback and support for learners experiencing burnout. Applying Kern's six-step approach to curriculum development, we created and implemented a …

Gsk-3Β As A Potential Coordinator Of Anabolic And Catabolic Pathways In Hepatitis C Virus Insulin Resistance, Gokul C Das, F Blaine Hollinger

Faculty, Staff and Students Publications

INTRODUCTION: Chronic hepatitis C infection can result in insulin resistance (IR). We have previously shown that it occurs through the interaction of pathways for glucose homeostasis, insulin signaling, and autophagy. But it is not known how soon the pathways are activated and how IR is related to the signals generated by catabolic and anabolic conditions occurring in infected cells. We have extended our studies to a cell culture system mimicking acute infection and to downstream pathways involving energy-sensor AMPK and nutrient-sensor mTOR that are active in catabolic and anabolic processes within the infected cells.

METHODS: Huh7 liver cells in culture …