Hepatology Commons^™

The Predictive Performance Of Contemporary Guideline Recommendations For Helicobacter Pylori Testing In A United States Population, Theresa Nguyen Wenker, Frederick B Peng, Ikenna Emelogu, Niharika Mallepally, Fasiha Kanwal, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

BACKGROUND: The Houston Consensus Conference and American College of Gastroenterology (ACG) have recommended Helicobacter pylori screening in United States populations with specific risk factors. However, the performance of these guidelines in clinical practice is not known.

METHODS: We identified consecutive patients undergoing upper endoscopy with gastric biopsies for any indication in a safety-net hospital in Houston, TX during January 2015-December 2016. We tested the association between the presence of H pylori (histopathology, stool antigen, urea breath test, immunoglobulin G serology, or prior treatment) and H pylori risk factors using logistic regression models, reported as odds ratios and 95% confidence intervals …

Tumor Biology And Immune Infiltration Define Primary Liver Cancer Subsets Linked To Overall Survival After Immunotherapy, Anuradha Budhu, Erica C Pehrsson, Aiwu He, Lipika Goyal, Robin Kate Kelley, Hien Dang, Changqing Xie, Cecilia Monge, Mayank Tandon, Lichun Ma, Mahler Revsine, Laura Kuhlman, Karen Zhang, Islam Baiev, Ryan Lamm, Keyur Patel, David E Kleiner, Stephen M Hewitt, Bao Tran, Jyoti Shetty, Xiaolin Wu, Yongmei Zhao, Tsai-Wei Shen, Sulbha Choudhari, Yuliya Kriga, Kris Ylaya, Andrew C Warner, Elijah F Edmondson, Marshonna Forgues, Tim F Greten, Xin Wei Wang

Kimmel Cancer Center Faculty Papers

Primary liver cancer is a rising cause of cancer deaths in the US. Although immunotherapy with immune checkpoint inhibitors induces a potent response in a subset of patients, response rates vary among individuals. Predicting which patients will respond to immune checkpoint inhibitors is of great interest in the field. In a retrospective arm of the National Cancer Institute Cancers of the Liver: Accelerating Research of Immunotherapy by a Transdisciplinary Network (NCI-CLARITY) study, we use archived formalin-fixed, paraffin-embedded samples to profile the transcriptome and genomic alterations among 86 hepatocellular carcinoma and cholangiocarcinoma patients prior to and following immune checkpoint inhibitor treatment. …

Reducing The Environmental Impact Of Surgery On A Global Scale: Systematic Review And Co-Prioritization With Healthcare Workers In 132 Countries, National Institute For Health And Care Research Global Health Research Unit On Global Surgery

Faculty, Staff and Student Publications

BACKGROUND: Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres.

METHODS: This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their …

5s Rrna Pseudogene Transcripts Are Associated With Interferon Production And Inflammatory Responses In Alcohol-Associated Hepatitis, Jianguo Wu, Adam Kim, Xiaoqin Wu, Semanti Ray, Daniela S Allende, Nicole Welch, Annette Bellar, Jaividhya Dasarathy, Srinivasan Dasarathy, Laura E Nagy

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Interferon (IFN) signaling is critical to the pathogenesis of alcohol-associated hepatitis (AH), yet the mechanisms for activation of this system are elusive. We hypothesize that host-derived 5S rRNA pseudogene (RNA5SP) transcripts regulate IFN production and modify immunity in AH.

APPROACH AND RESULTS: Mining of transcriptomic datasets revealed that in patients with severe alcohol-associated hepatitis (sAH), hepatic expression of genes regulated by IFNs was perturbed and gene sets involved in IFN production were enriched. RNA5SP transcripts were also increased and correlated with expression of type I IFNs. Interestingly, inflammatory mediators upregulated in sAH, but not in other liver …

Clinical Spectrum And Genetic Causes Of Mitochondrial Hepatopathy Phenotype In Children, James E Squires, Alexander G Miethke, C Alexander Valencia, Kieran Hawthorne, Lisa Henn, Johan L K Van Hove, Robert H Squires, Kevin Bove, Simon Horslen, Rohit Kohli, Jean P Molleston, Rene Romero, Estella M Alonso, Jorge A Bezerra, Stephen L Guthery, Evelyn Hsu, Saul J Karpen, Kathleen M Loomes, Vicky L Ng, Philip Rosenthal, Krupa Mysore, Kasper S Wang, Marisa W Friederich, John C Magee, Ronald J Sokol, Childhood Liver Disease Research Network (Children)

Faculty, Staff and Students Publications

BACKGROUND: Alterations in both mitochondrial DNA (mtDNA) and nuclear DNA genes affect mitochondria function, causing a range of liver-based conditions termed mitochondrial hepatopathies (MH), which are subcategorized as mtDNA depletion, RNA translation, mtDNA deletion, and enzymatic disorders. We aim to enhance the understanding of pathogenesis and natural history of MH.

METHODS: We analyzed data from patients with MH phenotypes to identify genetic causes, characterize the spectrum of clinical presentation, and determine outcomes.

RESULTS: Three enrollment phenotypes, that is, acute liver failure (ALF, n = 37), chronic liver disease (Chronic, n = 40), and post-liver transplant (n = 9), were analyzed. …

Probiotics And Human Milk Differentially Influence The Gut Microbiome And Nec Incidence In Preterm Pigs, Valeria Melendez Hebib, Diana H Taft, Barbara Stoll, Jinxin Liu, Lee Call, Gregory Guthrie, Nick Jensen, Amy B Hair, David A Mills, Douglas G Burrin

Faculty, Staff and Students Publications

Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. Major risk factors include prematurity, formula feeding, and gut microbial colonization. Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. In this study, we evaluated the effect of the probiotic Bifidobacterium longum subsp. infantis (BL. infantis), alone and in combination with a human milk oligosaccharide (HMO)—sialylactose (3′SL)—on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. We studied 50 …

Cachexia, Chorea, And Pain In Chronic Nonbacterial Osteitis And Inflammatory Bowel Disease: A Case Report, Ladan Agharokh, Katherine Mamola, Andrew G Yu, Annette L Medina, Bhaskar Gurram, Julie Fuller, Jason Y Park, Weina Chen, Veena Rajaram, Matthew R Hammer, Jeff L Waugh

Faculty, Staff and Student Publications

BACKGROUND: Inflammatory bowel disease is an inflammatory disorder that primarily impacts the gastrointestinal tract, leading to malnutrition and chronic microscopic intestinal blood loss. Uncontrolled systemic inflammation can impact other parts of the body, known as extraintestinal manifestations. Up to 25% of patients with inflammatory bowel disease are reported to have these complications in their skin, joints, bones, eyes, liver, lung, and pancreas (Rogler et al. in Gastroenterology 161(4):1118-1132, 2021). Neurologic involvement as extraintestinal manifestations are less common, reported at 3-19%, including neuropathies, demyelination, and cerebrovascular events (Morís in World J Gastroenterol. 20(5):1228-1237, 2014).

CASE PRESENTATION: A 13-year-old Caucasian boy presented …

Prospective Hemophilia Inhibitor Pup Study Reveals Distinct Antibody Signatures During Fviii Inhibitor Eradication, Helmut Paul, Verena Berg, Bagirath Gangadharan, Joel Bowen, Petra Lebeau, Jan Blatný, Christoph Male, Vlad C Radulescu, Rosa Diaz, Maria Elisa Mancuso, Deborah L Brown, Birgit M Reipert

Faculty, Staff and Student Publications

Factor VIII (FVIII) inhibitor formation is a major clinical concern during replacement therapy in patients with hemophilia A. Immune tolerance induction (ITI) is the only therapeutic approach to attempt inhibitor eradication and establishment of long-term immune tolerance to FVIII. Hemophilia Inhibitor Previously Untreated Patient (PUP) Study (HIPS) was a prospective clinical trial to investigate changes in the immune system of PUPs with severe hemophilia A. Five patients who developed persistent FVIII inhibitors during HIPS entered an ITI extension arm (HIPS-ITI). During HIPS-ITI, inhibitor patients received ITI with the same FVIII product (a single source of recombinant, human full-length FVIII) used …

Elevated Bile Acids Are Associated With Left Ventricular Structural Changes In Biliary Atresia, Manpreet K Virk, Muhammad Umair M Mian, Dalia A Bashir, John K Wilkes, Tobias Schlingman, Saul Flores, Curtis Kennedy, Fong Lam, Ayse A Arikan, Trung Nguyen, Krupa Mysore, Nhu Thao Nguyen Galvan, Jorge Coss-Bu, Saul J Karpen, Sanjiv Harpavat, Moreshwar S Desai

Faculty, Staff and Students Publications

BACKGROUND: In children with biliary atresia (BA), pathologic structural changes within the heart, which define cirrhotic cardiomyopathy, are associated with adverse perioperative outcomes. Despite their clinical relevance, little is known about the pathogenesis and triggers of pathologic remodeling. Bile acid excess causes cardiomyopathy in experimental cirrhosis, but its role in BA is poorly understood.

METHODS: Echocardiographic parameters of left ventricular (LV) geometry [LV mass (LVM), LVM indexed to height, left atrial volume indexed to BSA (LAVI), and LV internal diameter (LVID)] were correlated with circulating serum bile acid concentrations in 40 children (52% female) with BA listed for transplantation. A …

Neighborhood-Level Factors Contribute To Disparities In Hepatocellular Carcinoma Incidence In Texas, Abiodun O Oluyomi, Hashem B El-Serag, Adegboyega Olayode, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Texas has the highest hepatocellular carcinoma (HCC) incidence rates in the continental United States, but these rates vary by race-ethnicity. We examined racial-ethnic disparities through a geospatial analysis of the social determinants of health.

METHODS: Using data from the Texas Cancer Registry, we assembled 11,547 HCC cases diagnosed between 2011 and 2015 into Texas's census tracts geographic units. Twenty-nine neighborhood measures representing demographics and socioeconomic, and employment domains were retrieved from the U.S. Census Bureau. We performed a series of aspatial and spatially weighted regression models to identify neighborhood-level characteristics associated with HCC risk.

RESULTS: We found …

The Prevalence And Determinants Of Nafld And Mafld And Their Severity In The Va Primary Care Setting, Aaron P Thrift, Theresa H Nguyen, Codey Pham, Maya Balakrishnan, Fasiha Kanwal, Rohit Loomba, Hao T Duong, David Ramsey, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: A recent panel of international experts proposed the disease acronym metabolic (dysfunction)-associated fatty liver disease (MAFLD) in lieu of nonalcoholic fatty liver disease (NAFLD). We aimed to estimate the burden of and risk factors for NAFLD and MAFLD, and to examine the concordance between definitions in a Veterans population.

METHODS: We conducted a cross-sectional study among randomly selected patients within primary care at the Houston Veterans Affairs (VA) facility. Participants completed a survey, provided blood, and underwent Fibroscan. In the absence of heavy alcohol, hepatitis C virus and hepatitis B virus, a controlled attenuation parameter median ≥290 …

Exploration Of Associations Among Dietary Tryptophan, Microbiome Composition And Function, And Symptom Severity In Irritable Bowel Syndrome, Anna M Plantinga, Kendra J Kamp, Qinglong Wu, Li Chen, Linda Yoo, Robert L Burr, Kevin C Cain, Daniel Raftery, Fausto Carnevale Neto, Shyam Badu, Sik Yu So, Tor Savidge, Robert J Shulman, Margaret M Heitkemper

Faculty, Staff and Students Publications

BACKGROUND: Imbalance of the tryptophan (TRP) pathway may influence symptoms among patients with irritable bowel syndrome (IBS). This study explored relationships among different components that contribute to TRP metabolism (dietary intake, stool metabolite levels, predicted microbiome metabolic capability) in females with IBS and healthy controls (HCs). Within the IBS group, we also investigated relationships between TRP metabolic determinants, Bifidobacterium abundance, and symptoms of IBS.

METHODS: Participants with IBS (Rome III) and HCs completed a 28-day diary of gastrointestinal symptoms and a 3-day food record for TRP intake. They provided a stool sample for shotgun metagenomics, 16 S rRNA analyses, and …

Why The Vonoprazan Helicobacter Pylori Therapies In The Us-European Trial Produced Unacceptable Cure Rates, David Y Graham

Faculty, Staff and Students Publications

INTRODUCTION: Helicobacter pylori infects a large percentage of the world's population and is etiologically related to gastric cancer. The U.S. Food and Drug Administration recently approved two 14-day vonoprazan-containing regimens (vonoprazan-amoxicillin with or without clarithromycin) for H. pylori infections in the United States/Europe.

METHODS: We critically reviewed the trial methods to discover why the results were unacceptable low [i.e., no regimen achieved clinically acceptable (≥ 90%) or even conditionally acceptable cure rates (≥ 85%)]. Cure rates with antibiotic susceptible strains were 84.7 for vonoprazan triple therapy, 78.5 for vonoprazan-amoxicillin, and 78.7 for lansoprazole triple therapy, respectively. As was previously shown …

Comparative Analysis Of Opioid Use Between Robotic And Open Pancreatoduodenectomy, Russell G Witt, Yuki Hirata, Laura R Prakash, Timothy E Newhook, Jessica E Maxwell, Michael P Kim, Hop S Tran Cao, Jeffrey E Lee, Jean-Nicolas Vauthey, Matthew H G Katz, Ching-Wei D Tzeng, Naruhiko Ikoma

Faculty, Staff and Student Publications

BACKGROUND/PURPOSE: Risk-stratified pancreatectomy clinical pathways using regional anesthesia and multimodality analgesia have decreased overall opioid use, but the additional benefits of robotic surgery in opioid reduction for pancreatoduodenectomy (PD) are unknown. We compared the inpatient opioid use between robotic PD and open PD.

METHODS: Patients undergoing open PD within a protocol evaluating preincisional regional anesthetic block bundles were compared to consecutively-treated patients undergoing robotic PD identified from a prospectively maintained single-institutional database. Clinical characteristics, operative outcomes, pain scores and inpatient oral morphine equivalent (OME) use were compared between patients treated with robotic or open PD. Patients with a history of …

Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation In Preterm Pigs, Line I Christiansen, Bo Holmqvist, Xiaoyu Pan, Kristine Holgersen, Sandy E H Lindholm, Nicole L Henriksen, Douglas G Burrin, David Ley, Thomas Thymann, Per Torp Sangild, Stanislava Pankratova

Faculty, Staff and Students Publications

Very preterm infants show low levels of insulin-like growth factor-1 (IGF-1), which is associated with postnatal growth restriction and poor neurologic outcomes. It remains unknown whether supplemental IGF-1 may stimulate neurodevelopment in preterm neonates. Using cesarean-delivered preterm pigs as a model of preterm infants, we investigated the effects of supplemental IGF-1 on motor function and on regional and cellular brain development. Pigs were treated with 2.25 mg/kg/d recombinant human IGF-1/IGF binding protein-3 complex from birth until day 5 or 9 before the collection of brain samples for quantitative immunohistochemistry (IHC), RNA sequencing, and quantitative PCR analyses. Brain protein synthesis was …

Clinical Implications Of Molecular Drug Resistance Testing For Mycobacterium Tuberculosis: A 2023 Tbnet/Resist-Tb Consensus Statement, José Domínguez, Martin J Boeree, Emmanuelle Cambau, Dumitru Chesov, Francesca Conradie, Vivian Cox, Keertan Dheda, Andrii Dudnyk, Maha R Farhat, Sebastien Gagneux, Martin P Grobusch, Matthias I Gröschel, Lorenzo Guglielmetti, Irina Kontsevaya, Berit Lange, Frank Van Leth, Christian Lienhardt, Anna M Mandalakas, Florian P Maurer, Matthias Merker, Paolo Miotto, Barbara Molina-Moya, Florence Morel, Stefan Niemann, Nicolas Veziris, Andrew Whitelaw, Charles R Horsburgh, Christoph Lange

Faculty, Staff and Students Publications

Drug-resistant tuberculosis is a substantial health-care concern worldwide. Despite culture-based methods being considered the gold standard for drug susceptibility testing, molecular methods provide rapid information about the Mycobacterium tuberculosis mutations associated with resistance to anti-tuberculosis drugs. This consensus document was developed on the basis of a comprehensive literature search, by the TBnet and RESIST-TB networks, about reporting standards for the clinical use of molecular drug susceptibility testing. Review and the search for evidence included hand-searching journals and searching electronic databases. The panel identified studies that linked mutations in genomic regions of M tuberculosis with treatment outcome data. Implementation of molecular …

Admixture Mapping In African Americans Identifies New Risk Loci For Hcv-Related Cirrhosis, Hyun-Seok Kim, Priya B Shetty, Spiridon Tsavachidis, Jing Dong, Christopher I Amos, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Cirrhosis is the main predisposing condition for hepatocellular carcinoma. Host genetic risk factors have been reported for cirrhosis; however, whether there is a genetic contribution to racial disparities in cirrhosis requires further investigation.

METHODS: We used an affected-only mapping by admixture linkage disequilibrium analysis to characterize the genetic risk of cirrhosis in 227 African American patients with cirrhosis genotyped at 19,804 ancestry-informative marker single nucleotide polymorphisms. We additionally performed analyses stratified by hepatitis C virus (HCV) infection status. To replicate our findings, we conducted a case-control analysis in an external study population (452 cases and 196 controls). …

The Risk Of Hepatocellular Carcinoma In Entecavir Versus Tenofovir Treated Us Cohort With Chronic Hepatitis B Virus, Jennifer R Kramer, Peter A Richardson, Hyunseok Kim, Yao-Chun Hsu, Fasiha Kanwal, Hashem B El-Serag

Faculty, Staff and Students Publications

The comparative effectiveness of tenofovir (TDF) versus entecavir (ETV) in reducing the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (HBV) remains unclear. Data from a retrospective Korean cohort study published by Choi et al. initially suggested lower than expected incidence of HCC in patients on long-term TDF. However, additional studies from Korea did not show a statistically significant difference in HCC incidence rate between TDF and ETV groups, and subsequent studies reported mixed results ranging from no association or a slight advantage for TDF⁴. Most of these studies examined Asian patients from Korea, Taiwan, …

Clinical Features And Shared Mechanisms Of Chronic Gastritis And Osteoporosis, Tao Han, Yili Zhang, Baoyu Qi, Ming Chen, Kai Sun, Xiaokuan Qin, Bowen Yang, He Yin, Aili Xu, Xu Wei, Liguo Zhu

Faculty, Staff and Student Publications

Chronic gastritis (CG) and osteoporosis (OP) are common and occult diseases in the elderly and the relationship of these two diseases have been increasingly exposed. We aimed to explore the clinical characteristics and shared mechanisms of CG patients combined with OP. In the cross-sectional study, all participants were selected from BEYOND study. The CG patients were included and classified into two groups, namely OP group and non-OP group. Univariable and multivariable logistic regression methods were used to evaluate the influencing factors. Furthermore, CG and OP-related genes were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified …

Partnering With Patients And Families Living With Chronic Conditions To Coproduce Diagnostic Safety Through Ourdx: A Previsit Online Engagement Tool, Sigall K Bell, Zhiyong J Dong, Catherine M Desroches, Nicholas Hart, Stephen Liu, Brianna Mahon, Long H Ngo, Eric J Thomas, Fabienne Bourgeois

Faculty, Staff and Student Publications

OBJECTIVE: Patients and families are key partners in diagnosis, but methods to routinely engage them in diagnostic safety are lacking. Policy mandating patient access to electronic health information presents new opportunities. We tested a new online tool ("OurDX") that was codesigned with patients and families, to determine the types and frequencies of potential safety issues identified by patients/families with chronic health conditions and whether their contributions were integrated into the visit note.

METHODS: Patients/families at 2 US healthcare sites were invited to contribute, through an online previsit survey: (1) visit priorities, (2) recent medical history/symptoms, and (3) potential diagnostic concerns. …

Performance Of Six Clinical Physiological Scoring Systems In Predicting In-Hospital Mortality In Elderly And Very Elderly Patients With Acute Upper Gastrointestinal Bleeding In Emergency Department, Po-Han Wu, Shang-Kai Hung, Chien-An Ko, Chia-Peng Chang, Cheng-Ting Hsiao, Jui-Yuan Chung, Hao-Wei Kou, Wan-Hsuan Chen, Chiao-Hsuan Hsieh, Kai-Hsiang Ku, Kai-Hsiang Wu

Faculty, Staff and Student Publications

Background and Objectives: The aim of this study is to compare the performance of six clinical physiological-based scores, including the pre-endoscopy Rockall score, shock index (SI), age shock index (age SI), Rapid Acute Physiology Score (RAPS), Rapid Emergency Medicine Score (REMS), and Modified Early Warning Score (MEWS), in predicting in-hospital mortality in elderly and very elderly patients in the emergency department (ED) with acute upper gastrointestinal bleeding (AUGIB). Materials and Methods: Patients older than 65 years who visited the ED with a clinical diagnosis of AUGIB were enrolled prospectively from July 2016 to July 2021. The six scores were calculated …

Risk Factors For Hcc In Contemporary Cohorts Of Patients With Cirrhosis, Fasiha Kanwal, Saira Khaderi, Amit G Singal, Jorge A Marrero, Nicole Loo, Sumeet K Asrani, Christopher I Amos, Aaron P Thrift, Xiangjun Gu, Michelle Luster, Abeer Al-Sarraj, Jing Ning, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Etiological risk factors for cirrhosis have changed in the last decade. It remains unclear to what extent these trends in cirrhosis risk factors have changed HCC risk.

APPROACH AND RESULTS: We used data from two contemporary, prospective multiethnic cohorts of patients with cirrhosis: the Texas Hepatocellular Carcinoma Consortium Cohort and the Houston Veterans Administration Cirrhosis Surveillance Cohort. Patients with cirrhosis were enrolled from seven US centers and followed until HCC diagnosis, transplant, death, or June 30, 2021. We calculated the annual incidence rates for HCC and examined the effects of etiology, demographic, clinical, and lifestyle factors on …

Risk Factors And Prognostic Significance Of Platelet Count Abnormalities In Children With Hiv Infection On Antiretroviral Therapy, Joseph Lubega, Taylor O Kim, Gladstone Airewele, Amanda Grimes, Shaun Bulsara, Erin Peckham, Sebastian R Wanless, Heather Haq, Peter Elyanu, Philippa Musoke, Mwita Lumumba, Adeodata Kekitiinwa, Mogomotsi Matshaba, Michael Scheurer, Jenny Despotovic

Faculty, Staff and Students Publications

OBJECTIVES: To establish the incidence, risk factors and correlation with survival of thrombocytopenia and thrombocytosis (T/T) among children with HIV infection (CWH).

DESIGN: A retrospective nested case control study of patients 0-18 years in five Baylor International Pediatric AIDS Initiative (BIPAI) centers in sub-Sahara Africa, 2004-2014.

METHODS: Clinical and laboratory variables including complete blood counts (CBC) were extracted from the BIPAI electronic medical record system. Incident cases of T/T were identified and frequency-matched on follow-up time with controls with normal platelets. We calculated the prevalence and incidence density of T/T and used conditional logistic regression to evaluate their association with …

Clinical Course And Outcomes Of Patients With Nonalcoholic Fatty Liver Disease-Related Hepatocellular Cancer (Nafld-Hcc), Jinna Chu, George Cholankeril, Xian Yu, Abbas Rana, Yamini Natarajan, Hashem B El-Serag, Jennifer Kramer, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Among etiologies for hepatocellular (HCC), nonalcoholic fatty liver disease (NAFLD) carries a high risk of competing non-cancer mortality. The effect of cancer and non-cancer factors on risk of death after NAFLD-HCC diagnosis remains unclear. We aimed to evaluate the role of non-cancer mortality with NAFLD-HCC.

METHODS: Using a retrospective cohort of patients with NAFLD diagnosed at 130 facilities in the Veterans Administration, we identified patients with incident HCC diagnosed between January 1, 2005 and June 30, 2018. We determined cause of death as HCC-related, non-HCC liver-related, and non-liver-related after HCC diagnosis. We used Cox proportional hazards regression …

Fibroblast Growth Factor 19 Secretion And Function In Perinatal Development, Caitlin Vonderohe, Gregory Guthrie, Douglas G Burrin

Faculty, Staff and Students Publications

Limited work has focused on fibroblast growth factor-19 (FGF19) secretion and function in the perinatal period. FGF19 is a potent growth factor that coordinates development of the brain, eye, inner ear, and skeletal system in the embryo, but after birth, FGF19 transitions to be an endocrine regulator of the classic pathway of hepatic bile acid synthesis. FGF19 has emerged as a mediator of metabolism and bile acid synthesis in aged animals and adults in the context of liver disease and metabolic dysfunction. FGF19 has also been shown to have systemic insulin-sensitizing and skeletal muscle hypertrophic effects when induced or supplemented …

Serum Bile Acids As A Prognostic Biomarker In Biliary Atresia Following Kasai Portoenterostomy, Sanjiv Harpavat, Kieran Hawthorne, Kenneth D R Setchell, Monica Narvaez Rivas, Lisa Henn, Charlotte A Beil, Saul J Karpen, Vicky L Ng, Estella M Alonso, Jorge A Bezerra, Stephen L Guthery, Simon Horslen, Kathy M Loomes, Patrick Mckiernan, John C Magee, Robert M Merion, Jean P Molleston, Philip Rosenthal, Richard J Thompson, Kasper S Wang, Ronald J Sokol, Benjamin L Shneider, Childhood Liver Disease Research Network (Children)

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: In biliary atresia, serum bilirubin is commonly used to predict outcomes after Kasai portoenterostomy (KP). Infants with persistently high levels invariably need liver transplant, but those achieving normalized levels have a less certain disease course. We hypothesized that serum bile acid levels could help predict outcomes in the latter group.

APPROACH AND RESULTS: Participants with biliary atresia from the Childhood Liver Disease Research Network were included if they had normalized bilirubin levels 6 months after KP and stored serum samples from the 6-month post-KP clinic visit ( n = 137). Bile acids were measured from the stored …

Improved Survival After Liver Transplantation For Patients With Human Immunodeficiency Virus (Hiv) And Hiv/Hepatitis C Virus Coinfection In The Integrase Strand Transfer Inhibitor And Direct-Acting Antiviral Eras, Jake Sheraj Jacob, Anjiya Shaikh, Karthik Goli, Nicole E Rich, Jihane N Benhammou, Aijaz Ahmed, Donghee Kim, Abbas Rana, John A Goss, Susanna Naggie, Tzu-Hao Lee, Fasiha Kanwal, George Cholankeril

Faculty, Staff and Students Publications

BACKGROUND: People with human immunodeficiency virus (HIV) with and without hepatitis C virus (HCV) coinfection had poor outcomes after liver transplant (LT). Integrase strand transfer inhibitors (INSTIs) and direct-acting antivirals (DAAs) have changed the treatment landscape for HIV and HCV, respectively, but their impact on LT outcomes remains unclear.

METHODS: This retrospective analysis of adults with HIV monoinfection (n = 246) and HIV/HCV coinfection (n = 286) who received LT compared mortality in patients with HIV who received LT before versus after approval of INSTIs and in patients with HIV/HCV coinfection who received LT before versus after approval of DAAs. …

Hepatocytes Demarcated By Ephb2 Contribute To The Progression Of Nonalcoholic Steatohepatitis, Yang Xiao, Kirill Batmanov, Wenxiang Hu, Kun Zhu, Alexander Y Tom, Dongyin Guan, Chunjie Jiang, Lan Cheng, Sam J Mccright, Eric C Yang, Matthew R Lanza, Yifan Liu, David A Hill, Mitchell A Lazar

Faculty, Staff and Students Publications

Current therapeutic strategies for treating nonalcoholic steatohepatitis (NASH) have failed to alleviate liver fibrosis, which is a devastating feature leading to hepatic dysfunction. Here, we integrated single-nucleus transcriptomics and epigenomics to characterize all major liver cell types during NASH development in mice and humans. The bifurcation of hepatocyte trajectory with NASH progression was conserved between mice and humans. At the nonalcoholic fatty liver (NAFL) stage, hepatocytes exhibited metabolic adaptation, whereas at the NASH stage, a subset of hepatocytes was enriched for the signatures of cell adhesion and migration, which were mainly demarcated by receptor tyrosine kinase ephrin type B receptor …

A Method Using Longitudinal Laboratory Data To Predict Future Intestinal Complication In Patients With Crohn's Disease, James Irwin, Anton Lord, Emma Ferguson, Lisa A Simms, Katherine Hanigan, Carlos A Montoya, Graham Radford-Smith

Faculty, Staff and Student Publications

Background

Stenosis, fistulization, and perforation of the bowel are severe outcomes which can occur in patients with Crohn’s disease. Accurate prediction of these events may enable clinicians to alter treatment strategies and avoid these outcomes.

Aims

To study the correlation between longitudinal laboratory testing and subsequent intestinal complications in patients with Crohn’s disease.

Methods

An observational cohort of patients with Crohn’s disease at a single center were analyzed between 01/01/1994 and 06/30/2016. A complication was defined as the development of an intestinal fistula, stenosis, or perforation. Exploratory analysis using Cox regression was performed to select the best statistical method to …

Serum Biomarkers Correlated With Liver Stiffness Assessed In A Multicenter Study Of Pediatric Cholestatic Liver Disease, Daniel H Leung, Sridevi Devaraj, Nathan P Goodrich, Xinpu Chen, Deepthi Rajapakshe, Wen Ye, Victor Andreev, Charles G Minard, Danielle Guffey, Jean P Molleston, Lee M Bass, Saul J Karpen, Binita M Kamath, Kasper S Wang, Shikha S Sundaram, Philip Rosenthal, Patrick Mckiernan, Kathleen M Loomes, M Kyle Jensen, Simon P Horslen, Jorge A Bezerra, John C Magee, Robert M Merion, Ronald J Sokol, Benjamin L Shneider, Estella Alonso, Lee Bass, Susan Kelly, Mary Riordan, Hector Melin-Aldana, Jorge Bezerra, Kevin Bove, James Heubi, Alexander Miethke, Greg Tiao, Julie Denlinger, Erin Chapman, Ronald Sokol, Amy Feldman, Cara Mack, Michael Narkewicz, Frederick Suchy, Shikha S Sundaram, Johan Van Hove, Benigno Garcia, Mikaela Kauma, Kendra Kocher, Matthew Steinbeiss, Mark Lovell, Kathleen M Loomes, David Piccoli, Elizabeth Rand, Pierre Russo, Nancy Spinner, Jessi Erlichman, Samantha Stalford, Dina Pakstis, Sakya King, Robert Squires, Rakesh Sindhi, Veena Venkat, Kathy Bukauskas, Patrick Mckiernan, Lori Haberstroh, James Squires, Philip Rosenthal, Laura Bull, Joanna Curry, Camille Langlois, Grace Kim, Jeffery Teckman, Vikki Kociela, Rosemary Nagy, Shraddha Patel, Jacqueline Cerkoski, Jean P Molleston, Molly Bozic, Girish Subbarao, Ann Klipsch, Cindy Sawyers, Oscar Cummings, Simon P Horslen, Karen Murray, Evelyn Hsu, Kara Cooper, Melissa Young, Laura Finn, Binita M Kamath, Vicky Ng, Claudia Quammie, Juan Putra, Deepika Sharma, Aishwarya Parmar, Stephen Guthery, Kyle Jensen, Ann Rutherford, Amy Lowichik, Linda Book, Rebecka Meyers, Tyler Hall, Kasper S Wang, Sonia Michail, Danny Thomas, Catherine Goodhue, Rohit Kohli, Larry Wang, Nisreen Soufi, Daniel Thomas, Saul Karpen, Nitika Gupta, Rene Romero, Miriam B Vos, Rita Tory, John-Paul Berauer, Carlos Abramowsky, Jeanette Mcfall, Benjamin L Shneider, Sanjiv Harpavat, Paula Hertel, Daniel Leung, Mary Tessier, Deborah Schady, Laurel Cavallo, Diego Olvera, Christina Banks, Cynthia Tsai, Richard Thompson, Edward Doo, Jay Hoofnagle, Averell Sherker, Rebecca Torrance, Sherry Hall, John Magee, Robert Merion, Cathie Spino, Wen Ye

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.

APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM …