Hepatology Commons^™

Functional, Diagnostic And Therapeutic Aspects Of Bile, Monjur Ahmed

Division of Gastroenterology and Hepatology Faculty Papers

Bile is a unique body fluid synthesized in our liver. Enterohepatic circulation preserves bile in our body through its efficient synthesis, transport, absorption, and reuptake. Bile is the main excretory route for bile salts, bilirubin, and potentially harmful exogenous lipophilic substances. The primary way of eliminating cholesterol is bile. Although bile has many organic and inorganic contents, bile acid is the most physiologically active component. Bile acids have a multitude of critical physiologic functions in our body. These include emulsification of dietary fat, absorption of fat and fat-soluble vitamins, maintaining glucose, lipid, and energy homeostasis, sustenance of intestinal epithelial integrity …

Cardiac Metastasis After Curative Treatment Of Hepatocellular Carcinoma: Risk Factors, Treatment Options, And Prognosis, Gaurav Jain, Mathew Otto, Mubeen Khan Mohammed Abdul, Manpreet Chadha, Ajay Sahajpal

Journal of Patient-Centered Research and Reviews

Hepatocellular carcinoma (HCC) is primary hepatic malignancy with a high incidence of recurrence. The risk of recurrence directly correlates to patient’s overall prognosis. Management of advanced HCC involves a combination of surgical resection, locoregional therapy, and systemic treatment. Distant metastases are rare, and intraventricular cardiac metastases are even more infrequent. This brief review details an illustrative case of cardiac metastasis after curative treatment of primary HCC and then summarizes the literature on risk factors, treatment options, and patient prognosis in the setting of distant metastases from HCC. Prognosis of metastasis to the heart is generally poor, and available evidence emphasizes …

Assessment Of Predictive Factors Of Hepatic Steatosis Diagnosed By Vibration Controlled Transient Elastography (Vcte) In Chronic Hepatitis C Virus-Infected Patients, Singh Y, Gogtay M, Gurung S, Trivedi N, Abraham Gm

Journal of Community Hospital Internal Medicine Perspectives

This retrospective, cross-sectional study aimed to evaluate the predictive factors of moderate/severe hepatic steatosis diagnosed by vibration-controlled transient elastography (VCTE). It included 158 adult patients with suspected non-alcoholic fatty liver disease (NAFLD) evaluated by VCTE in an outpatient setting of a community-based teaching hospital. Patients with significant alcohol consumption, oral contraceptive use, hepatitis B disease, autoimmune hepatitis, and primary biliary cirrhosis were excluded. Steatosis was categorized as S0-S1 (mild) and S2-S3 (moderate/severe) based on the controlled attenuation parameter (CAP) score. Results demonstrated the mean values of BMI (p=0.001), kiloPascals [kPa] (fibrosis) raw score (p=0.009), obesity (p=0.001), diabetes mellitus [DM] (p=0.014), …

Changing Global Epidemiology Of Liver Cancer From 2010 To 2019: Nash Is The Fastest Growing Cause Of Liver Cancer, Daniel Q Huang, Amit G Singal, Yuko Kono, Darren J H Tan, Hashem B El-Serag, Rohit Loomba

Faculty, Staff and Students Publications

Liver cancer epidemiology is changing due to increasing alcohol consumption, rising prevalence of obesity, and advances in hepatitis B virus (HBV) and hepatitis C virus (HCV) treatment. However, the impact of these changes on global liver cancer burden remains unclear. We estimated global and regional temporal trends in the burden of liver cancer and the contributions of various liver disease etiologies using the methodology framework of the Global Burden of Disease study. Between 2010 and 2019, there was a 25% increase in liver cancer deaths. Age-standardized death rates (ASDRs) increased only in the Americas and remained stable or fell in …

Regulation Of Pgc1Α Downstream Of The Insulin Signaling Pathway Plays A Role In The Hepatic Proteotoxicity Of Mutant Α1-Antitrypsin Deficiency Variant Z, David A Rudnick, Jiansheng Huang, Tunda Hidvegi, Andrew S Chu, Pamela Hale, Admire Munanairi, Dennis J Dietzen, Paul F Cliften, Eric Tycksen, Andrew J Lutkewitte, Brian N Finck, Stephen C Pak, Gary A Silverman, David H Perlmutter

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Insulin signaling is known to regulate essential proteostasis mechanisms.

METHODS: The analyses here examined effects of insulin signaling in the PiZ mouse model of α1-antitrypsin deficiency in which hepatocellular accumulation and proteotoxicity of the misfolded α1-antitrypsin Z variant (ATZ) causes liver fibrosis and cancer.

RESULTS: We first studied the effects of breeding PiZ mice to liver-insulin-receptor knockout (LIRKO) mice (with hepatocyte-specific insulin-receptor gene disruption). The results showed decreased hepatic ATZ accumulation and liver fibrosis in PiZ x LIRKO vs PiZ mice, with reversal of those effects when we bred PiZ x LIRKO mice onto a FOXO1-deficient background. …

Mediating Effects Of Neighborhood-Level Socioeconomic Deprivation On The Association Between Race/Ethnicity And Advanced Hepatocellular Carcinoma, Abiodun O Oluyomi, Kusha A Mohammadi, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Racial/ethnic minorities are more likely than non-Hispanic whites (NHW) to be diagnosed with advanced stage hepatocellular carcinoma (HCC). We examined the role of neighborhood disadvantage as a mediator of the association between race/ethnicity and HCC stage at diagnosis.

METHODS: We used data from HCC cases diagnosed in Texas from 2007 to 2015. HCC cases were classified as local versus regional/advanced stage. A mediation model approach was used to estimate the average direct effect, average mediated (indirect) effect, total effect, and proportion mediated by the Area Deprivation Index (ADI), a composite measure of disadvantage.

RESULTS: 7,622 had local while 6303 …

Pilot Phase Results Of A Prospective, Randomized Controlled Trial Of Narrowband Ultraviolet B Phototherapy In Hospitalized Covid-19 Patients, Frank H Lau, Catherine E Powell, Giacomo Adonecchi, Denise M Danos, Andrew R Dinardo, Robert J Chugden, Peter Wolf, Carmen F Castilla

Faculty, Staff and Students Publications

COVID-19 morbidity and mortality are driven by poor immune regulation. Narrowband ultraviolet B (NB-UVB) phototherapy is standard of care in a number of immune-dysregulated diseases. To assess the efficacy of NB-UVB phototherapy for improving COVID-19 outcomes in high-risk, hospitalized, we developed the Adaptive Photo-Protection Trial. This is a multi-center, prospective, double-blinded, randomized, placebo-controlled trial. The pilot phase results are reported here. Consecutive patients admitted with a positive COVID-19 PCR were screened for eligibility. Enrolled subjects were computer randomized 1:1 to NB-UVB or placebo phototherapy. Subjects were treated daily with escalating doses on 27% of their body surface area for up …

Crispr Detection Of Circulating Cell-Free Mycobacterium Tuberculosis Dna In Adults And Children, Including Children With Hiv: A Molecular Diagnostics Study, Zhen Huang, Sylvia M Lacourse, Alexander W Kay, Joshua Stern, Jaclyn N Escudero, Brady M Youngquist, Wenshu Zheng, Debrah Vambe, Muyalo Dlamini, Godwin Mtetwa, Lisa M Cranmer, Irene Njuguna, Dalton C Wamalwa, Elizabeth Maleche-Obimbo, Donald G Catanzaro, Christopher J Lyon, Grace John-Stewart, Andrew Dinardo, Anna M Mandalakas, Bo Ning, Tony Y Hu

Faculty, Staff and Students Publications

BACKGROUND: Tuberculosis remains a leading cause of global mortality, especially for adults and children living with HIV (CLHIV) underdiagnosed by sputum-based assays. Non-sputum-based assays are needed to improve tuberculosis diagnosis and tuberculosis treatment monitoring. Our aim in this study was to determine whether ultrasensitive detection of Mycobacterium tuberculosis cell-free DNA (Mtb-cfDNA) in blood can diagnose tuberculosis and evaluate tuberculosis treatment responses.

METHODS: In this molecular diagnostics study we analysed archived serum from two patient populations evaluated for tuberculosis in Eswatini and Kenya to detect Mtb-cfDNA, analysing serum from all individuals who had both sufficient serum volumes and clear diagnostic results. …

Cholestasis Alters Brain Lipid And Bile Acid Composition And Compromises Motor Function In Neonatal Piglets, Nicole Lind Henriksen, Svend Høime Hansen, Matthew Domenic Lycas, Xiaoyu Pan, Thomas Eriksen, Lars Søndergaard Johansen, Richard R Sprenger, Christer Stenby Ejsing, Douglas G Burrin, Kerstin Skovgaard, Vibeke Brix Christensen, Thomas Thymann, Stanislava Pankratova

Faculty, Staff and Students Publications

Infants with neonatal cholestasis are prone to neurodevelopmental deficits, however, the underlying pathogenesis is unclear. Lipid malabsorption and accumulation of potentially neurotoxic molecules in the blood such as bile acids are important yet relatively unexplored pathways. Here, we developed a translational piglet model to understand how the molecular bile acid and lipid composition of the brain is affected by this disease and relates to motor function. Piglets (8-days old) had bile duct ligation or sham surgery and were fed a formula diet for 3 weeks. Alongside sensory-motor deficits observed in bile duct-ligated animals, we found a shift toward a more …

Postprandial Symptoms In Patients With Symptoms Of Gastroparesis: Roles Of Gastric Emptying And Accommodation, Henry P Parkman, Mark L Van Natta, Alan H Maurer, Kenneth L Koch, Madhusudan Grover, Zubair Malik, Irene Sarosiek, Thomas L Abell, Robert Bulat, Braden Kuo, Robert J Shulman, Gianrico Farrugia, Laura Miriel, James Tonascia, Frank Hamilton, Pankaj J Pasricha, Richard W Mccallum

Faculty, Staff and Students Publications

Patients often are evaluated for gastroparesis because of symptoms occurring with meals. Gastric emptying scintigraphy (GES) is used for gastroparesis diagnosis, although results are not well correlated with gastroparesis symptoms. The aim of this study is to assess relationships between gastroparesis symptoms, gastric emptying (GE), and gastric accommodation (GA). Patients with symptoms of gastroparesis completed the Patient Assessment of Upper GI Symptoms (PAGI-SYM) and recorded symptoms during GES and water load satiety test (WLST), an indirect assessment for GA. A total of 109 patients with gastroparesis symptoms were assessed. Symptom severity increased after GES meal for stomach fullness, belching, nausea, …

Opposing Roles Of Hdac6 In Liver Regeneration And Hepatocarcinogenesis, Sophors Phorl, Azra Memon, Yuri Seo, Thi Oanh Hoang, Trung Nghia Tran, Le Minh Tri Nguyen, Chang Hoon Lee, Woon Kyu Lee, Joo-Yong Lee

Faculty, Staff and Student Publications

Histone deacetylase 6 (HDAC6), a deacetylase of p53, has emerged as a privileged inhibitory target for cancer therapy because of its deacetylating activity for p53 at K120 and K373/382. However, intricate roles of HDAC6 in hepatocellular carcinogenesis have been suggested by recent evidence, namely that HDAC6 ablation suppresses innate immunity, which plays critical roles in tumor immunosurveillance and antitumor immune responses. Therefore, it is valuable to determine whether HDAC6 ablation inhibits hepatocellular carcinogenesis using in vivo animal models. Here, we firstly showed that HDAC6 ablation increased K320 acetylation of p53, known as pro-survival acetylation, in all tested animal models but …

Pathogenesis Of Tuberculosis: The 1930 Lübeck Disaster Revisited, Peter Donald, Stefan Kaufmann, Stephanie Thee, Anna Maria Mandalakas, Christoph Lange

Faculty, Staff and Students Publications

During the 1930 Lübeck Mycobacterium bovis bacille Calmette–Guérin (BCG) disaster, 251 neonates received three oral BCG doses accidentally contaminated by virulent Mycobacterium tuberculosis; 67 (26.7%) infants died of tuberculosis. BCG reversion to pathogenicity did not occur. Detailed post mortem examinations clarified contested aspects of tuberculosis pathogenesis. Gastrointestinal infection was seldom “silent” and did not cause typical primary pulmonary lesions. In 15 infants, primary pulmonary foci were found but these resulted from vaccine ingestion and aspiration and were not caused by gastrointestinal infection spreading to the lungs without trace of its journey, as claimed by prominent researchers such as Calmette …

Fecal Microbiota Transplantation In Decompensated Cirrhosis: A Systematic Review On Safety And Efficacy, Annie S. Hong, Kyaw Min Tun, Jenny M. Hong, Kavita Batra, Gordon Ohning

Department of Internal Medicine Faculty Research

Background and Aims: Due to increasing knowledge of the “gut–liver axis”, there has been growing interest regarding the use of fecal microbiota transplant in the management of chronic liver disease. There are limited data available and current guidelines are mostly based on expert opinions. We aim to perform the first systematic review investigating safety and efficacy of fecal microbiota transplant particularly among high-risk decompensated cirrhosis patient populations. Methods: Literature search was performed using variations of the keywords “fecal microbiota transplant” and “cirrhosis” on PubMed/Medline from inception to 3 October 2021. The resulting 116 articles were independently screened by two authors. …

Maternal And Fetal Bile Acid Homeostasis Regulated By Sulfated Progesterone Metabolites Through Fxr Signaling Pathway In A Pregnant Sow Model, Peng Wang, Peiqiang Yuan, Sen Lin, Heju Zhong, Xiaoling Zhang, Yong Zhuo, Jian Li, Lianqiang Che, Bin Feng, Yan Lin, Shengyu Xu, De Wu, Douglas G Burrin, Zhengfeng Fang

Faculty, Staff and Students Publications

Abnormally elevated circulating bile acids (BA) during pregnancy endanger fetal survival and offspring health; however, the pathology and underlying mechanisms are poorly understood. A total of nineteen pregnant sows were randomly assigned to day 60 of gestation, day 90 of gestation (G60, G90), and the farrowing day (L0), to investigate the intercorrelation of reproductive hormone, including estradiol, progesterone and sulfated progesterone metabolites (PMSs), and BA in the peripheral blood of mother and fetuses during pregnancy. All data were analyzed by Student’s t-test or one-way ANOVA of GraphPad Prism and further compared by using the Student–Newman–Keuls test. Correlation analysis was …

Host Gut Resistome In Gulf War Chronic Multisymptom Illness Correlates With Persistent Inflammation, Dipro Bose, Somdatta Chatterjee, Ethan Older, Ratanesh Seth, Patricia Janulewicz, Punnag Saha, Ayan Mondal, Jeffrey M Carlson, Alan W Decho, Kimberly Sullivan, Nancy Klimas, Stephen Lasley, Jie Li, Saurabh Chatterjee

Faculty, Staff and Student Publications

Chronic multisymptom illness (CMI) affects a subsection of elderly and war Veterans and is associated with systemic inflammation. Here, using a mouse model of CMI and a group of Gulf War (GW) Veterans' with CMI we show the presence of an altered host resistome. Results show that antibiotic resistance genes (ARGs) are significantly altered in the CMI group in both mice and GW Veterans when compared to control. Fecal samples from GW Veterans with persistent CMI show a significant increase of resistance to a wide class of antibiotics and exhibited an array of mobile genetic elements (MGEs) distinct from normal …

Risk For Post-Colonoscopy Irritable Bowel Syndrome In Patients With And Without Antibiotic Exposure: A Retrospective Cohort Study, Ravy K Vajravelu, Jordan M Shapiro, Josephine Ni, Shivani U Thanawala, James D Lewis, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Laboratory studies have demonstrated that antibiotic use in conjunction with bowel purgatives causes alterations to the gut microbiota. Because gut microbiota changes may be a trigger for the development of irritable bowel syndrome (IBS), we sought to assess whether individuals who undergo bowel cleansing for colonoscopy and have concurrent antibiotic exposure develop IBS at higher rates than individuals who undergo colonoscopy without antibiotic exposure.

METHODS: We used data from Optum's de-identified Clinformatics Data Mart Database in the United States to study a cohort of 50- to 55-year-olds who underwent screening colonoscopy. Individuals exposed to antibiotics within 14 …

Role Of The Chemokine System In Liver Fibrosis: A Narrative Review, Kyle L Poulsen, Christina K Cajigas-Du Ross, Jarod K Chaney, Laura E Nagy

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVE: Liver fibrosis is a disease with characteristics of an aberrant wound healing response. Fibrosis is commonly the end-stage for chronic liver diseases like alcohol-associated liver disease (ALD), metabolic-associated liver disease, viral hepatitis, and hepatic autoimmune disease. Innate immunity contributes to the progression of many diseases through multiple mechanisms including production of pro-inflammatory mediators, leukocyte infiltration and tissue injury. Chemokines and their receptors orchestrate accumulation and activation of immune cells in tissues and are associated with multiple liver diseases; however, much less is known about their potential roles in liver fibrosis. This is a narrative review of current …

Using Artificial Neural Networks To Predict Intra-Abdominal Abscess Risk Post-Appendectomy, Morouge M Alramadhan, Hassan S Al Khatib, James R Murphy, Kuojen Tsao, Michael L Chang

Faculty, Staff and Student Publications

OBJECTIVE: To determine if artificial neural networks (ANN) could predict the risk of intra-abdominal abscess (IAA) development post-appendectomy.

BACKGROUND: IAA formation occurs in 13.6% to 14.6% of appendicitis cases with "complicated" appendicitis as the most common cause of IAA. There remains inconsistency in describing the severity of appendicitis with variation in treatment with respect to perforated appendicitis.

METHODS: Two "reproducible" ANN with different architectures were developed on demographic, clinical, and surgical information from a retrospective surgical dataset of 1574 patients less than 19 years old classified as either negative (n = 1,328) or positive (n = 246) for IAA post-appendectomy …

A Systematic Review Of The Efficacy And Safety Of Fecal Microbiota Transplantation In The Treatment Of Hepatic Encephalopathy And Clostridioides Difficile Infection In Patients With Cirrhosis, Kyaw Min Tun, Annie S. Hong, Kavita Batra, Yassin Naga, Gordon Ohning

Department of Internal Medicine Faculty Research

The microbiome of the human gut and liver coexists by influencing the health and disease state of each system. Fecal microbiota transplantation (FMT) has recently emerged as a potential treatment for conditions associated with cirrhosis, such as hepatic encephalopathy and recurrent/refractory Clostridioides difficile infection (rCDI). We have conducted a systematic review of the safety and efficacy of FMT in treating hepatic encephalopathy and rCDI. A literature search was performed using variations of the keywords “fecal microbiota transplant” and “cirrhosis” on PubMed/MEDLINE from inception to October 3, 2021. The resulting 116 articles were independently reviewed by two authors. Eight qualifying studies …

Moving Through Loss: The Experience Of Ambiguous Loss With Hospitalized Children, The Development Of A Method, Peyton Edington

Expressive Therapies Capstone Theses

The current method examined the effects of ambiguous loss with medical transplant patients in a pediatric hospital by utilizing a dance/movement therapy intervention. The development of this method was based on ambiguous loss theory with a dance/movement therapy approach. The explored literature identified central themes of ambiguous loss, such as resilience. These themes were connected to the practice of dance/movement therapy, such as embodiment. With this connection, the intervention was developed and implemented with participants. The central themes that emerged from the intervention were change, loss, meaning-making, and hope. One child and two adolescents were participants in this intervention, and …