Hepatology Commons^™

Platelet-Derived Thrombospondin 1 Promotes Immune Cell Liver Infiltration And Exacerbates Diet-Induced Steatohepatitis, Taesik Gwag, Sangderk Lee, Zhenyu Li, Alana Newcomb, Josephine Otuagomah, Steven A. Weinman, Ying Liang, Changcheng Zhou, Shuxia Wang

UK CARES Faculty Publications

Background & Aims: Recent studies have implicated platelets, particularly a-granules, in the development of non-alcoholic steatohepatitis (NASH). However, the specific mechanisms involved have yet to be determined. Notably, thrombospondin 1 (TSP1) is a major component of the platelet a-granules released during platelet activation. Hence, we aimed to determine the role of platelet-derived TSP1 in NASH.

Methods: Platelet-specific Tsp1 knockout mice (TSP1Dpf4 ) and their wild-type littermates (TSP1 F/F) were used. NASH was induced by feeding the mice with a diet enriched in fat, sucrose, fructose, and cholesterol (AMLN diet). A human liver NASH organoid model was also employed.

Results: Although …

Elongation Of Very Long Chain Fatty Acids-3 (Elovl3) Is Activated By Zhx2 And Is A Regulator Of Cell Cycle Progression, Kate Townsend Creasy, Hui Ren, Jieyun Jiang, Martha L. Peterson, Brett T. Spear

Markey Cancer Center Faculty Publications

Zinc fingers and homeoboxes 2 (Zhx2) are transcriptional regulators of liver gene expression with key functions in embryonic development as well as tissue regeneration in response to damage and disease, presumably through its control of target genes. Previous microarray data suggested that elongation of very long chain fatty acids-3 (Elovl3), a member of the ELOVL family of enzymes that synthesize very long chain fatty acids (VLCFAs), is a putative Zhx2 target gene. VLCFAs are core component of ceramides and other bioactive sphingolipids that are often dysregulated in diseases and regulate key cellular processes including proliferation. Since several previously identified Zhx2 …

Liver Transplantation For Biliary Cysts: Perioperative And Long-Term Outcomes, Gabriel Orozco, Malay B. Shah, Meera Gupta, Francesc Marti, Xiaonan Mei, Alexandre Ancheta, Siddharth Desai, Michael Cavnar, B. Mark Evers, Joseph B. Zwischenberger, Roberto Gedaly

Markey Cancer Center Faculty Publications

Background: Biliary cysts (BC) is a rare indication for orthotopic liver transplantation (OLT).

Methods: We queried the UNOS dataset to identify patients who underwent OLT for Caroli’s disease (CD) and choledochal cysts (CC). All patients with BC (CD + CC) were compared to a cohort of patients transplanted for other indications. Patients with CC were also compared to those with CD. Cox proportional hazard model was performed to assess predictors of graft and patient survival.

Results: 261 patients underwent OLT for BC. Patients with BC had better pre-operative liver function compared to those transplanted for other indications. 5-year graft and …

Ketohexokinase-C Regulates Global Protein Acetylation To Decrease Carnitine Palmitoyltransferase 1a-Mediated Fatty Acid Oxidation, Robert N. Helsley, Se-Hyung Park, Hemendra J. Vekaria, Patrick G. Sullivan, Lindsey R. Conroy, Ramon Sun, María Del Mar Romero, Laura Herrero, Joanna Bons, Christina D. King, Jacob Rose, Jesse G. Meyer, Birgit Schilling, C. Ronald Kahn, Samir Softic

Saha Cardiovascular Research Center Faculty Publications

Background & Aims: The consumption of sugar and a high-fat diet (HFD) promotes the development of obesity and metabolic dysfunction. Despite their well-known synergy, the mechanisms by which sugar worsens the outcomes associated with a HFD are largely elusive. Methods: Six-week-old, male, C57Bl/6 J mice were fed either chow or a HFD and were provided with regular, fructose- or glucose-sweetened water. Moreover, cultured AML12 hepatocytes were engineered to overexpress ketohexokinase-C (KHK–C) using a lentivirus vector, while CRISPR-Cas9 was used to knockdown CPT1a. The cell culture experiments were complemented with in vivo studies using mice with hepatic overexpression of KHK–C and …

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 …

Prevalence And Types Of Drugs Used Among Hepatitis A Patients During Outbreaks Associated With Person-To-Person Transmission, Kentucky, Michigan, And West Virginia, 2016–2019, Megan G. Hofmeister, Alice Asher, Christopher M. Jones, Ryan J. Augustine, Cole Burkholder, Jim Collins, Monique A. Foster, Shannon Mcbee, Erica D. Thomasson, Doug Thoroughman, Mark K. Weng, Philip R. Spradling

Journal of Appalachian Health

Background: People who use drugs are at increased risk for hepatitis A virus infection. Since 1996, the Advisory Committee on Immunization Practices has recommended hepatitis A vaccination for people who use drugs. Since 2016, the U.S. has experienced widespread hepatitis A outbreaks associated with person-to-person transmission.

Purpose: To describe the prevalence of drug use, route of use, and drugs used among hepatitis A outbreak-associated patients.

Methods: State outbreak and medical records were reviewed to describe the prevalence, type, and route of drug use among a random sample of 812 adult outbreak-associated hepatitis A patients from Kentucky, Michigan, and West Virginia …

Gut Microbial Trimethylamine Is Elevated In Alcohol-Associated Hepatitis And Contributes To Ethanol-Induced Liver Injury In Mice, Robert N. Helsley, Tatsunori Miyata, Anagha Kadam, Venkateshwari Varadharajan, Naseer Sangwan, Emily C. Huang, Rakhee Banerjee, Amanda L. Brown, Kevin K. Fung, William J. Massey, Chase Neumann, Danny Orabi, Lucas J. Osborn, Rebecca C. Schugar, Megan R. Mcmullen, Annette Bellar, Kyle L. Poulsen, Adam Kim, Vai Pathak, Marko Mrdjen

Pediatrics Faculty Publications

There is mounting evidence that microbes residing in the human intestine contribute to diverse alcohol-associated liver diseases (ALD) including the most deadly form known as alcohol-associated hepatitis (AH). However, mechanisms by which gut microbes synergize with excessive alcohol intake to promote liver injury are poorly understood. Furthermore, whether drugs that selectively target gut microbial metabolism can improve ALD has never been tested. We used liquid chromatography tandem mass spectrometry to quantify the levels of microbe and host choline co-metabolites in healthy controls and AH patients, finding elevated levels of the microbial metabolite trimethylamine (TMA) in AH. In subsequent studies, we …

Increasing Staff Compliance With Routine Hcv Screening And Improving Linkage To Care Among Patients Testing Hepatitis C Positive In The Emergency Department, Carson G. Swartz

DNP Projects

Background: Hepatitis C virus (HCV) is a blood-borne pathogen that can cause severe liver disease, cancer, and death and is a significant source of morbidity and mortality in the United States. Several academic medical centers including University of Kentucky Healthcare have implemented routine HCV screening for patients presenting to the emergency department (ED) and have discovered a large viral burden amongst patients who are often symptomatic.

Purpose: The purpose of this doctoral project is to increase staff compliance, confidence, and education regarding the HCV screening process in an urban, Level I emergency department, as well as to evaluate whether an …

Thalidomide For The Treatment Of Metastatic Hepatic Epithelioid Hemangioendothelioma: A Case Report With A Long Term Follow-Up, Felipe Salech, Sebastián Valderrama, Bruno Nervi, Juan Carlos Rodriguez, Danny Oksenberg, Alvaro Koch, Gladys Smok, Ignacio Duarte, Rosa María Pérez-Ayuso, Nicolás Jarufe, Jorge Martínez, Alejandro Soza, Marco Arrese, Arnoldo Riquelme

Internal Medicine Faculty Publications

Hepatic epithelioid hemangioendothelioma (HEH) is an unusual, low-grade malignant vascular tumor of the liver. Here we describe a case of a 40-year-old woman who presented with abdominal pain in the upper right quadrant and giant hepatomegaly, in which imaging studies and a fine-needle liver biopsy confirmed the presence of a large EHE with an isolated lung metastasis. After balancing all possible therapeutic modalities the patient was treated conservatively with thalidomide (300 mg/day). The drug was well tolerated with minimal toxicity and thepatient continues on therapy 109 months after treatment was started with no disease progression. Current therapeutic options for HEH …

Parallel Transjugular Intrahepatic Portosystemic Shunt With Viatorr® Stents For Primary Tips Insufficiency: Case Series And Review Of Literature, Driss Raissi, Qian Yu, Michael Nisiewicz, Steven Krohmer

Radiology Faculty Publications

BACKGROUND

Transjugular intrahepatic portosystemic shunts (TIPS) can alleviate complications of portal hypertension such as ascites and variceal bleeding by decreasing the portosystemic gradient. In limited clinical situations, parallel TIPS may be only solution to alleviate either variceal bleeding or ascites secondary to portal hypertension when the primary TIPS fails to do so. Data specifically addressing the use of this partially polytetrafluoroethylene covered nitinol stent (Viatorr^®) is largely lacking despite Viatorr^® being the current gold standard for modern TIPS placement.

CASE SUMMARY

All three patients had portal hypertension and already had a primary Viatorr^® TIPS placed previously. …

Interdependency Of Egf And Glp-2 Signaling In Attenuating Mucosal Atrophy In A Mouse Model Of Parenteral Nutrition, Yongjia Feng, Farok R. Demehri, Weidong Xiao, Yu-Hwai Tsai, Jennifer C. Jones, Constance D. Brindley, David W. Threadgill, Jens J. Holst, Bolette Hartmann, Terrence A. Barrett, Daniel H. Teitelbaum, Peter J. Dempsey

Internal Medicine Faculty Publications

BACKGROUND & AIMS: Total parenteral nutrition (TPN), a crucial treatment for patients who cannot receive enteral nutrition, is associated with mucosal atrophy, barrier dysfunction, and infectious complications. Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) improve intestinal epithelial cell (IEC) responses and attenuate mucosal atrophy in several TPN models. However, it remains unclear whether these 2 factors use distinct or overlapping signaling pathways to improve IEC responses. We investigated the interaction of GLP-2 and EGF signaling in a mouse TPN model and in patients deprived of enteral nutrition.

METHODS: Adult C57BL/6J, IEC-Egfr^{knock out (KO)} and IEC-pik3r1^KO mice receiving …

Systemic-To-Pulmonary Artery Pressure Ratio As A Predictor Of Patient Outcome Following Liver Transplantation, Annette Rebel, Dung Nguyen, Brooke Bauer, Paul A. Sloan, Amy Dilorenzo, Zaki-Udin Hassan

Anesthesiology Faculty Publications

AIM To assess the value of the mean systemic-to-pulmonary artery pressure (MAP/mPAP) ratio for predicting outcomes following orthotopic liver transplant (OLT).

METHODS A retrospective data analysis was performed and data (mean arterial blood pressure, mean pulmonary artery pressure and Cardiac Index) were collected at several points during OLT. Outcomes evaluated were duration of postoperative endotracheal intubation [ET; minutes after intensive care unit (ICU) arrival], length of ICU stay, total hospitalization and frequency of immediate postoperative complications. A total of 91 patients were included in the data analysis. Based on the intraoperative course of the MAP/mPAP ratio, 2 hemodynamic responses were …

A Prospective Analysis Of Factors Associated With Decreased Physical Activity In Patients With Cirrhosis Undergoing Transplant Evaluation, Anna Christina Dela Cruz, Valery Vilchez, Sooyeon Kim, Benjamin Barnes, Abhishek Ravinuthala, Anthony Zanni, Roberto Galuppo, Achuthan Sourianarayanane, Trushar Patel, Erin Colleen Maynard, Malay B. Shah, Michael F. Daily, Timothy L. Uhl, Karyn A. Esser, Roberto Gedaly

Internal Medicine Faculty Publications

BACKGROUND: Physical activity has been associated with improved recovery time after transplantation. Handgrip strength has been related to post-transplant outcomes.

AIM: To evaluate predictors of physical activity and grip strength in cirrhotic patients undergoing liver transplant evaluation.

METHODS: Single center, prospective analysis.

RESULTS: A hundred patients were evaluated (54% male, mean age 53 ± 9). Common etiologies of liver disease were non-alcoholic hepatitis (27%), hepatitis C (22%), and alcoholic liver disease (21%). Mean MELD score was 13.5. Forty one percent had a history of smoking. Ninety-three patients completed the International Physical Activity Questionnaire. The median total physical activity score of …

Primary And Secondary Prevention Of Hepatitis C Virus Among Rural Appalachian People Who Use Drugs, Dustin B. Stephens

Theses and Dissertations--Clinical and Translational Science

Hepatitis C virus (HCV) remains a major cause of morbidity and mortality worldwide, with 3% of the global population chronically infected. Clinical impacts in the United States are projected to increase for two decades, and mortality attributed to HCV now exceeds HIV. Injection drug use (IDU) is the most common route of transmission in the developed world. Advances in treatment offer hope of mitigating HCV impacts, but substantial barriers obstruct people who inject drugs (PWID) from receiving care, particularly in medically underserved regions including Central Appalachia. This study assessed IDU paraphernalia sharing longitudinally over 24 months in a sample of …

Co-Regulation Of Expression Of Phase Ii Metabolizing Enzymes And Multidrug Resistance-Associated Protein 2, Viviana A. Catania, Enrique J. Sánchez Pozzi, Marcelo G. Luquita, María L. Ruiz, Silvina S. M. Villanueva, Brett Jones, Aldo D. Mottino

Toxicology and Cancer Biology Faculty Publications

Treatment of experimental animals with prototypical enzyme inducers represents a useful tool to characterize the role of different isozymes in drug metabolism and to improve our knowledge on factors regulating their synthesis at the transcriptional level. The effect of model enzyme inducers on phase II (conjugating) enzyme families, including UDP-glucuronosyltransferase’s and glutathione-S-transferase’s, has been well characterized in rodent liver. More recently, the effect of inducers on the expression of canalicular multidrug resistance-associated protein 2 (Mrp2) has been focused upon. The identification of a number of conjugated drugs as Mrp2 substrates suggests that both the conjugation and transport systems act coordinately …