Hepatology Commons^™

Optimization Of Kidney Health In Liver Transplant Candidates: Pretransplant Considerations And Modalities, Muhammad Y Jan, Kavish R Patidar, Marwan S Ghabril, Chandrashekhar A Kubal

Faculty, Staff and Students Publications

Patients with decompensated end-stage liver disease (ESLD) are at increased risk for mortality, and only liver transplantation (LT) offers meaningful hope for survival. These patients are at risk for kidney dysfunction through the continuum of care for ESLD including LT. We discuss the role of accurate estimation and measurement of baseline glomerular filtration rate in assessment of kidney dysfunction among those with ESLD. Optimizing kidney function is a vital goal in the management of these patients before LT. In this review, we summarize salient aspects of assessing and optimizing kidney function in this patient population. Precipitating factors and different causes …

Controversies In Terlipressin And Transplantation In The United States: How Do We Meld The Two?, Eric M Przybyszewski, Robert M Wilechansky, Paige Mclean Diaz, Andrew S Allegretti, Lisa B Vanwagner, Giuseppe Cullaro, Josh Levitsky, Pere Ginès, Salvatore Piano, Sumeet K Asrani, Kavish R Patidar, Hrs-Harmony Consortium

Faculty, Staff and Students Publications

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a severe complication of cirrhosis that carries a poor prognosis. The recent Food and Drug Administration approval of terlipressin has substantial implications for managing HRS-AKI and liver allocation in the United States. Terlipressin has been available in Europe for over a decade, and several countries have adapted policy changes such as Model for End-Stage Liver Disease (MELD) score "lock" for HRS-AKI. In this article, we outline the European experience with terlipressin use and explore the question of whether terlipressin treatment for HRS-AKI should qualify for the MELD score "lock" in the United States in …

An Electronic Health Record Model For Predicting Risk Of Hepatic Fibrosis In Primary Care Patients, Aaron P Thrift, Theresa H Nguyen Wenker, Kyler Godwin, Maya Balakrishnan, Hao T Duong, Rohit Loomba, Fasiha Kanwal, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND: One challenge for primary care providers caring for patients with nonalcoholic fatty liver disease is to identify those at the highest risk for clinically significant liver disease.

AIM: To derive a risk stratification tool using variables from structured electronic health record (EHR) data for use in populations which are disproportionately affected with obesity and diabetes.

METHODS: We used data from 344 participants who underwent Fibroscan examination to measure liver fat and liver stiffness measurement [LSM]. Using two approaches, multivariable logistic regression and random forest classification, we assessed risk factors for any hepatic fibrosis (LSM > 7 kPa) and significant hepatic …

Severe Febrile Neutropenia And Pancytopenia In A Patient With Advanced Hepatocellular Carcinoma Treated With Atezolizumab And Bevacizumab: A Case Report, Shadi Chamseddine, Michael Lapelusa, Kristen Carter, Van Nguyen, Yehia I Mohamed, Yara Sakr, Cristhiam M Rojas-Hernandez, Rikita I Hatia, Manal Hassan, John A Goss, Khaled M Elsayes, Asif Rashid, Ryan Sun, Hop Sanderson Tran Cao, Hesham M Amin, Ahmed O Kaseb

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs), agents that stimulate T-cell function, have become the standard first-line treatment for unresectable hepatocellular carcinoma (HCC). However, they may also cause immune-related adverse events (irAEs), which are rare and have not been extensively reported. Here, we describe a case of severe febrile neutropenia and pancytopenia after atezolizumab plus bevacizumab (atezo/bev) therapy and its treatment course.

CASE DESCRIPTION: The combination of atezo/bev was initiated as the first-line treatment for a man in his early 50s, who was diagnosed with unresectable HCC. The first treatment cycle was administered in the outpatient setting, and the patient developed a …

Trends, Predictors, And Outcomes Of Hepatic Encephalopathy Treatment At A Quaternary Transplant Center From 2012-2022, Patrick Twohig, Thoetchai Peeraphatdit, Kaeli Samson, Makayla Schissel, Lynette M. Smith, Kyaw Min Tun, Ellen Tan, Kyle Scholten, Jason Barbaretta, Kevin Brittan, Timothy Mccashland

Graduate Medical Education Research Journal

Background: Hepatic encephalopathy (HE) is a devastating complication of cirrhosis that increases mortality. Many patients do not receive guideline recommended HE treatment.

Our aim is to evaluate trends in HE treatment over time, variables associated with receiving treatment, and outcomes based on the type of treatment received.

Methods: Retrospective single-center cohort study of hospitalized patients with HE from July 2012 – June 2022. HE treatment was defined as receiving lactulose, rifaximin, or combination therapy.

Results: A total of 1,683 unique patients were included, 72% of patients received HE treatment. Fewer HE patients received any treatment in 2022 (65.9%) compared to …

In-Silico Analysis Of Tmem2 As A Pancreatic Adenocarcinoma And Cancer-Associated Fibroblast Biomarker, And Functional Characterization Of Nsc777201, For Targeted Drug Development, Prateeti Srivastava, Vijesh Kumar Yadav, Tzu-Hao Chang, Emily Chia-Yu Su, Bashir Lawal, Alexander Th Wu, Hsu-Shan Huang

Faculty, Staff and Student Publications

Pancreatic adenocarcinoma (PAAD), known as one of the deadliest cancers, is characterized by a complex tumor microenvironment, primarily comprised of cancer-associated fibroblasts (CAFs) in the extracellular matrix. These CAFs significantly alter the matrix by interacting with hyaluronic acid (HA) and the enzyme hyaluronidase, which degrades HA - an essential process for cancer progression and spread. Despite the critical role of this interaction, the specific functions of CAFs and hyaluronidase in PAAD development are not fully understood. Our study investigates this interaction and assesses NSC777201, a new anti-cancer compound targeting hyaluronidase. This research utilized computational methods to analyze gene expression data …

Hemojuvelin-Mediated Hepcidin Induction Requires Both Bone Morphogenetic Protein Type I Receptors Alk2 And Alk3, Deniz Y Dogan, Eugen I Urzica, Isabelle Hornung, Philipp Kastl, David Oguama, Franca M Fette, Lien H Nguyen, Frank Rosenbauer, Kai Zacharowski, Ursula Klingmüller, Elise Gradhand, Andreas Von Knethen, Rüdiger Popp, Ingrid Fleming, Lisa Schrader, Andrea U Steinbicker

Faculty, Staff and Student Publications

Hemojuvelin (HJV) is a glycosylphosphatidylinositol-anchored protein of the repulsive guidance molecule family acting as a bone morphogenetic protein (BMP) coreceptor to induce the hepatic iron regulatory protein hepcidin. Hepcidin causes ubiquitination and degradation of the sole known iron exporter ferroportin, thereby limiting iron availability. The detailed signaling mechanism of HJV in vivo has yet to be investigated. In the current manuscript, we used an established model of adeno-associated virus (AAV)-mediated liver-specific overexpression of HJV in murine models of hepatocyte-specific deficiency of the BMP type I receptors Alk2 or Alk3. In control mice, HJV overexpression increased hepatic Hamp messenger RNA (mRNA) …

Predicting Mortality Within 1 Year Of Art Initiation In Children And Adolescents Living With Hiv In Sub-Saharan Africa: A Retrospective Observational Cohort Study, Alexander Kay, Bhekumusa Lukhele, Sandile Dlamini, Abigail Seeger, Phumzile Dlamini, Sandile Ndabezitha, Nobuhle Mthethwa, Teresa Steffy, Lilian Komba, Pauline Amuge, Eunice Ketangenyi, Peter Elyanu, Adamson Munthali, Amos Msekandiana, Yvonne Maldonado, Elizabeth Chiao, Adeodata Kekitiinwa, Lineo Thahane, Lumumba Mwita, H Lester Kirchner, Anna Maria Mandalakas

Faculty, Staff and Students Publications

BACKGROUND: Differentiated service delivery (DSD) for children and adolescents living with HIV can improve targeted resource use. We derived a mortality prediction score to guide clinical decision making for children and adolescents living with HIV.

METHODS: Data for this retrospective observational cohort study were evaluated for all children and adolescents living with HIV and initiating antiretroviral therapy (ART); aged 0-19 years; and enrolled at Baylor clinics in Eswatini, Malawi, Lesotho, Tanzania, and Uganda between 2005 and 2020. Data for clinical prediction, including anthropometric values, physical examination, ART, WHO stage, and laboratory tests were captured at ART initiation. Backward stepwise variable …

Association Of Tea And Coffee Consumption And Biliary Tract Cancer Risk: The Biliary Tract Cancers Pooling Project, Yu-Han Huang, Erikka Loftfield, Ilona Argirion, Hans-Olov Adami, Demetrius Albanes, Andrew T Chan, Veronika Fedirko, Gary E Fraser, Neal D Freedman, Graham G Giles, Patricia Hartge, Verena Katzke, Synnove F Knutsen, James Lacey, Linda M Liao, Juhua Luo, Roger L Milne, Katie M O'Brien, Ulrike Peters, Jenny N Poynter, Mark P Purdue, Kim Robien, Sven Sandin, Dale P Sandler, Veronica W Setiawan, Jae H Kang, Tracey G Simon, Rashmi Sinha, Trang Vopham, Stephanie J Weinstein, Emily White, Xuehong Zhang, Bin Zhu, Katherine A Mcglynn, Peter T Campbell, Mei-Hsuan Lee, Jill Koshiol

Faculty, Staff and Student Publications

Background and aims: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence.

Approach and results: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and < 3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR< 3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers.

Conclusions: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.

Systemic Inflammatory Markers Of Persistent Cerebral Edema After Aneurysmal Subarachnoid Hemorrhage, Nadia Khan, Magdalena Kurnik-Łucka, Gniewomir Latacz, Krzysztof Gil

Faculty, Staff and Student Publications

In the first part of this article, the role of intestinal epithelial tight junctions (TJs), together with gastrointestinal dopaminergic and renin-angiotensin systems, are narratively reviewed to provide sufficient background. In the second part, the current experimental data on the interplay between gastrointestinal (GI) dopaminergic and renin-angiotensin systems in the regulation of intestinal epithelial permeability are reviewed in a systematic manner using the PRISMA methodology. Experimental data confirmed the copresence of DOPA decarboxylase (DDC) and angiotensin converting enzyme 2 (ACE2) in human and rodent enterocytes. The intestinal barrier structure and integrity can be altered by angiotensin (1-7) and dopamine (DA). Both …

Transcriptomic Signature, Bioactivity And Safety Of A Non-Hepatotoxic Analgesic Generating Am404 In The Midbrain Pag Region, Hernan A. Bazan, Surjyadipta Bhattacharjee, Madigan M. Reid, Bokkyoo Jun, Connor Polk, Madeleine Strain, Linsey A. St Pierre, Neehar Desai, Patrick W. Daly, Jessica A. Cucinello-Ragland, Scott Edwards, Javier Recio, Julio Alvarez-Builla, James J. Cai, Nicolas G. Bazan

School of Medicine Faculty Publications

Safe and effective pain management is a critical healthcare and societal need. The potential for acute liver injury from paracetamol (ApAP) overdose; nephrotoxicity and gastrointestinal damage from chronic non-steroidal anti-inflammatory drug (NSAID) use; and opioids’ addiction are unresolved challenges. We developed SRP-001, a non-opioid and non-hepatotoxic small molecule that, unlike ApAP, does not produce the hepatotoxic metabolite N-acetyl-p-benzoquinone-imine (NAPQI) and preserves hepatic tight junction integrity at high doses. CD-1 mice exposed to SRP-001 showed no mortality, unlike a 70% mortality observed with increasing equimolar doses of ApAP within 72 h. SRP-001 and ApAP have comparable antinociceptive effects, including the complete …

Parallel Use Of Low-Complexity Automated Nucleic Acid Amplification Tests On Respiratory Samples And Stool With Or Without Lateral Flow Lipoarabinomannan Assays To Detect Pulmonary Tuberculosis Disease In Children, Laura Olbrich, Alexander W Kay, Stephanie Bjerrum, Bada Yang, Johanna Åhsberg, Ruvandhi R Nathavitharana, Andreas Lundh, Maunank Shah, Devan Jaganath

Faculty, Staff and Students Publications

This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To compare the diagnostic accuracy of the parallel use of low-complexity automated nucleic acid amplification tests on respiratory and stool specimens in children and lateral flow urine lipoarabinomannan amongst children with HIV versus each assay alone for detecting pulmonary tuberculosis. Secondary objectives To compare the diagnostic accuracy of low-complexity automated nucleic acid amplification tests on respiratory and stool specimens in combination versus each sample type alone. To investigate the following sources of heterogeneity: clinical setting, signs and symptoms of pulmonary tuberculosis disease, screening positivity by chest …

Parallel Use Of Low-Complexity Automated Nucleic Acid Amplification Tests And Lateral Flow Urine Lipoarabinomannan Assays To Detect Tuberculosis Disease In Adults And Adolescents Living With Hiv, Stephanie Bjerrum, Bada Yang, Johanna Åhsberg, Ruvandhi R Nathavitharana, Laura Olbrich, Devan Jaganath, Alexander W Kay, Andreas Lundh, Maunank Shah

Faculty, Staff and Students Publications

This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To compare the diagnostic accuracy of parallel use of lateral flow urine lipoarabinomannan on urine and low-complexity automated nucleic acid amplification tests on respiratory samples versus each test alone for detection of tuberculosis disease in adults and adolescents living with HIV who present with presumptive tuberculosis. Secondary objectives To investigate the following sources of heterogeneity: clinical setting; signs and symptoms of tuberculosis; screening positivity for tuberculosis disease by chest x-ray, C-reactive protein elevation, and molecular World Health Organization-recommended rapid diagnostics; seriously ill; advanced HIV; and CD4 …

Recent Advances In The Prevention And Treatment Of Decompensated Cirrhosis And Acute-On-Chronic Liver Failure (Aclf) And The Role Of Biomarkers, Jonel Trebicka, Ruben Hernaez, Debbie Lindsay Shawcross, Alexander L Gerbes

Faculty, Staff and Students Publications

The progression of cirrhosis with clinically significant portal hypertension towards decompensated cirrhosis remains clinically challenging and the evolution towards acute-on-chronic liver failure (ACLF), with one or more extrahepatic organ failures, is associated with very high mortality. In the last decade, significant progress has been made in the understanding of the mechanisms leading to decompensation and ACLF. As portal hypertension advances, bacterial translocation across an impaired gut barrier culminates in endotoxaemia, systemic inflammation and cirrhosis-associated immune dysfunction (CAID). Gut-derived systemic inflammation and CAID have become the logical targets for innovative therapies that prevent hepatic decompensation episodes and the progression to ACLF.Furthermore, …

Effect Of Education Level On Adequacy Of Bowel Preparation Prior To Colonoscopy, Anna Chen, Md, Michael Dimarino, Md, Akash Patel, Do, Katherine Duffey, Md, Gregory Habig, Md, Aaron Martin, Md, Cuckoo Choudhary, Md, Stephanie Moleski, Md

Health Equity and Quality Improvement (HEQI) Summit

Background

• Adequate bowel preparation is crucial for obtaining a high-quality colonoscopy.
• Inadequate preparation leads to impaired visualization, which can lower adenoma detection rate, increase the risk of complications and potentially necessitate repeating the procedure.¹
• Patients with higher health literacy and a higher level of education have been associated with better bowel preparation quality.^2,3,4,5

Medication Access Barriers To Hepatitis C Anti-Viral Therapy Following Transplantation Of Hepatitis C Positive Donors Into Hepatitis C Negative Recipients, Harry Rockower, Md, Sarah Yeager, Pharmd, Jami Schulte, Pharmd, Dagan Coppock, Md, Jonathan Fenkel, Md, Katherine Belden, Md

Health Equity and Quality Improvement (HEQI) Summit

Background

• Over the past decade there has been a paradigm shift in solid organ transplantation with the use of Hepatitis C (HCV) positive donor organs for HCV negative recipients.
• This evaluation looks through the lens of insurance approval for direct acting antivirals (DAA) and the process needed for obtaining and ensuring affordability of these medications.
• While the AASLD/IDSA guidelines recommend early initiation of pangenotypic DAA therapy after organ transplant without the need to confirm recipient viral replication many centers often initiate the DAA approval process after viremia is detected due to insurance barriers.¹
• The process for obtaining insurance approval …

Clostridium Perfringens Sepsis From A Hepatic Abscess With Hemolysis And Renal Failure, Requiring Hemodialysis, Joel Collins Ii, Katelyn Courtney, James A. Espinosa, Alan Lucerna

Rowan-Virtua Research Day

The prognosis of sepsis caused by Clostridium perfringens is extremely poor, with a mortality rate of 70%-100%. Management includes antibiotic regimens specific to toxin production as well as source control via surgical or interventional mechanisms. We report a case of a 64-year-old male who presented with right upper quadrant (RUQ) abdominal pain and was diagnosed with Clostridium perfringens bacteremia with associated acalculous cholecystitis, hepatic abscess, and acute renal failure requiring hemodialysis. It is felt that early hemodialysis was an associated factor in the patient's survival.

Intrabiliary Metastasis Of Colorectal Mucinous Adenocarcinoma Mimicking Choledocholithiasis 18 Years After The Primary Tumor, Sumaya Abdul Ghaffar, David Pfau, Nikhil Madhuripan, Robert Christopher Harmon, Antonio Galvao Neto, Ana Luiza Gleisner

Faculty, Staff and Student Publications

This case report presents a 62-year-old male who had previously undergone curative colectomy and neoadjuvant chemotherapy in 2005 for colorectal cancer. He presented with jaundice, which was initially attributed to choledocholithiasis. After cholecystectomy and repeat ERCPs, hyperbilirubinemia persisted. There was persistent dilation of the right posterior duct on imaging, concerning for biliary stricture, possibly due to cholangiocarcinoma or intraductal papillary neoplasm. During a right posterior hepatectomy, a peripheral liver lesion was found in association with the dilated bile duct. On frozen evaluation, the lesion was found to be invasive adenocarcinoma. The final pathology was compatible with a metastatic mucinous adenocarcinoma …

Herbal And Dietary Supplement Induced Liver Injury Leading To Hepatitis-Associated Severe Aplastic Anemia: A Case Report, Rebecca Mercedes, Sanjiv Harpavat, Paula M Hertel, Ghadir Sasa, Susan Kirk, Kalyani Patel, Krupa R Mysore

Faculty, Staff and Students Publications

Herbal and dietary supplements (HDS) are a common etiology of drug induced liver injury and, specifically, Herbalife® supplements have been implicated. Hepatitis associated aplastic anemia (HAAA) is a rare and potentially fatal complication after acute hepatitis characterized by pancytopenia. While there have been rare cases of HDS leading to HAAA, no cases of Herbalife® induced liver injury leading to HAAA have been reported from this specific HDS. We report a unique case of severe aplastic anemia developing after sub-fulminant liver failure associated with chronic HDS use. This case illustrates the importance of warning the public about HDS as their use …

Gut Development Following Insulin-Like Growth Factor-1 Supplementation To Preterm Pigs, Martin Bo Rasmussen, Kristine Holgersen, Stanislava Pankratova, Ole Bæk, Douglas G Burrin, Thomas Thymann, Per Torp Sangild

Faculty, Staff and Students Publications

BACKGROUND: Reduced insulin-like growth factor-1 (IGF-1) levels may contribute to impaired organ development in preterm infants. Using preterm pigs as a model, we hypothesized that IGF-1 supplementation improves health and gut development during the first three weeks of life.

METHODS: First, clinical and organ endpoints were compared between artificially-reared, cesarean-delivered preterm pigs and vaginally-delivered, sow-reared term pigs at 5, 9 and 19 days. Next, preterm pigs were treated with recombinant human IGF-1 for 19 days (2.25 mg/kg/day, systemically).

RESULTS: Relative to term pigs, preterm pigs had lower body weight, fat, bone contents, relative weights of liver and spleen and a …