Hepatology Commons^™

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 …

Hepatocellular Carcinoma Incidence Threshold For Surveillance In Virologically Cured Hepatitis C Individuals, Jagpreet Chhatwal, Ali Hajjar, Peter P Mueller, Gizem Nemutlu, Neeti Kulkarni, Mary Linton B Peters, Fasiha Kanwal

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in hepatitis C individuals with cirrhosis if the HCC incidence rate is above 1.5 per 100 person-years (PY). However, the incidence threshold for surveillance in individuals who achieve a virologic cure is unknown. We estimated the HCC incidence rate above which routine HCC surveillance is cost-effective in this growing population of virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis.

METHODS: We developed a Markov-based microsimulation model of the natural history of HCC in individuals with hepatitis C who achieved virologic cure with oral direct-acting antivirals. We used …

Mincle-Gsdmd-Mediated Release Of Il-1Β Small Extracellular Vesicles From Hepatic Macrophages In Ethanol-Induced Liver Injury, Quanri Zhang, Weiwei Liu, Katarzyna Bulek, Han Wang, Megan R Mcmullen, Xiaoqin Wu, Nicole Welch, Renliang Zhang, Jaividhya Dasarathy, Srinivasan Dasarathy, Laura E Nagy, Xiaoxia Li

Faculty, Staff and Student Publications

BACKGROUND: Macrophage-inducible C-type lectin (Mincle) is expressed on hepatic macrophages and senses ethanol (EtOH)-induced danger signals released from dying hepatocytes and promotes IL-1β production. However, it remains unclear what and how EtOH-induced Mincle ligands activate downstream signaling events to mediate IL-1β release and contribute to alcohol-associated liver disease (ALD). In this study, we investigated the association of circulating β-glucosylceramide (β-GluCer), an endogenous Mincle ligand, with severity of ALD and examined the mechanism by which β-GluCer engages Mincle on hepatic macrophages to release IL-1β in the absence of cell death and exacerbates ALD.

METHOD AND RESULTS: Concentrations of β-GluCer were increased …

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

Faculty, Staff and Student Publications

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

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

High Prevalence Of Osteopathy In Chronic Pancreatitis: A Cross-Sectional Analysis From The Proceed Study, Phil A Hart, Dhiraj Yadav, Liang Li, Savi Appana, William Fisher, Evan Fogel, Chris E Forsmark, Walter G Park, Stephen Pandol, Mark D Topazian, Stephen K Van Den Eden, Santhi Swaroop Vege, David Bradley, Jose Serrano, Darwin L Conwell, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

osteopenia). However, existing literature is mostly limited to retrospective or administrative studies that have not clearly defined the prevalence and risk factors. Our aim was to identify patient- and disease-related associations with osteopathy in a prospective cohort study of CP.

Methods: We studied 282 subjects with definitive CP enrolled in the PROCEED study who had a baseline dual-energy X-ray absorptiometry (DXA) scan. Osteopenia and osteoporosis were defined using the lowest T-scores. Clinical data were collected using standardized case report forms. Comparisons were performed with a multivariate logistic regression model with forward selection to identify risk factors for osteopathy.

Results: The …

Hepatitis B Virus-Associated Hepatocellular Carcinoma And Chronic Stress, Nicholas Noverati, Rukaiya Bashir, Dina Halegoua-De Marzio, Hie-Won Hann

Department of Medicine Faculty Papers

The Hepatitis B virus is one of the most significant hepatocarcinogens globally. The carcinogenic mechanisms of this virus are complex, and may include interactions with the host's immune system. Certain factors, such as stress on the body, can also potentiate these mechanisms. Stress, although adaptive in an acute form, is deleterious to health when chronic and can both suppress and activate the host's defense system. In hepatocellular carcinoma, this can lead to tumor initiation and progression. Those that are more prone to stress, or exposed to situations that incite stress, may be at higher risk of developing cancer. Racial disparities, …

Willingness To Undergo A Repeat Liver Biopsy Among Hiv/Hepatitis C Virus-Coinfected And Hepatitis C Virus-Monoinfected Patients, Valerianna K Amorosa, Omowunmi Aibana, Norah J Shire, Zachariah Dorey-Stein, Thomas Ferrara, Joanne Gilmore, Jay R Kostman, Vincent Lo Re

Faculty, Staff and Student Publications

BACKGROUND: Guidelines for chronic hepatitis C virus (HCV) management have recommended that a liver biopsy be repeated at 3-year intervals for HIV/HCV-coinfected patients and 5-year intervals for those with HCV monoinfection to assess fibrosis progression. However, it is unclear if patients are willing to repeat this procedure.

OBJECTIVE: To determine the prevalence and factors, particularly HIV coinfection, associated with willingness to repeat a liver biopsy.

METHODS: A questionnaire was administered to 235 HCV-infected patients (113 with HIV coinfection) between January 2008 and June 2011 who previously underwent liver biopsy. The main outcome was self-reported willingness to repeat the biopsy. The …

Relative Telomere Length: A Novel Non-Invasive Biomarker For The Risk Of Non-Cirrhotic Hepatocellular Carcinoma In Patients With Chronic Hepatitis B Infection., Xiaoying Fu, Shaogui Wan, Hie-Won Hann, Md, Ronald E Myers, Phd, Richard S Hann, Jennifer Au, Bicui Chen, Jinliang Xing, Hushan Yang

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND AND AIMS: Telomere length has emerged as a promising risk predictor of various cancers including hepatocellular carcinoma (HCC). However, the majority of studies in this area measured telomere length in hepatocytes and one in lymphocytes with conflicting results. Moreover, no studies have been reported on using circulating DNA telomere length as a non-invasive HCC biomarker.

METHODS: We conducted a nested case-control study to determine the relative telomere length (RTL) in serum DNA from 140 hepatitis B virus (HBV)-related HCC cases and 280 frequency-matched cancer-free HBV controls.

RESULTS: Cases had a significantly longer RTL (median, 0.31; range, 0.02-2.31) than controls …

Hepatocellular Carcinoma Survival In Uninsured And Underinsured Patients, John A Harvin, George Van Buren, Kuojen Tsao, Putao Cen, Tien C Ko, Curtis J Wray

Faculty, Staff and Student Publications

BACKGROUND: The incidence of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC) is increasing. The purpose of this study is to establish baseline survival in a medically-underserved population and to evaluate the effect of HCV seropositivity on our patient population.

MATERIALS AND METHODS: We reviewed clinicopathologic parameters from a prospective tumor registry and medical records from the Harris County Hospital District (HCHD). Outcomes were compared using Kaplan-Meier survival analysis and log-rank tests.

RESULTS: A total of 298 HCC patients were identified. The median survival for the entire cohort was 3.4 mo. There was no difference in survival between the HCV …