Hepatology Commons^™

Surgical And Oncological Outcomes Of Hepatic Resection For Hepatocellular Carcinoma: Report From A Low Volume Centre In A Developing Country, Muhammad Rizwan Khan, Saleema Begum, Muhammad Tayyab Ul Hasan Siddiqui

Section of General Surgery

Objective: To review the surgical and oncological outcomes of patients who underwent hepatic resection for hepatocellular carcinoma (HCC).
Study design: Cohort study.
Place and duration of study: Department of Surgery of the Aga Khan University Hospital Karachi, from 2008 to 2019.
Methodology: Consecutive patients who underwent hepatic resection for HCC at the Hospital were included. The data were collected and analysed on aspects including demographics, liver function status, tumour characteristics, perioperative management, and surgical and oncological outcomes. Survival analyses were performed using the Kaplan-Meier method, and log-rank test was applied to determine the influence of variables on overall and disease-free …

Children With Functional Abdominal Pain Disorders Successfully Decrease Fodmap Food Intake On A Low Fodmap Diet With Modest Improvements In Nutritional Intake And Diet Quality, Vishnu Narayana, Ann R Mcmeans, Rona L Levy, Robert J Shulman, Bruno P Chumpitazi

Faculty, Staff and Students Publications

BACKGROUND: We sought to determine how a low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet (LFD) affected high FODMAP food intake, nutrient intake, and diet quality in children with functional abdominal pain disorders (FAPD).

METHODS: Children (ages 7-13 years) with Rome IV FAPD began a dietitian-guided LFD. Three-day food records were captured at baseline and 2-3 weeks into the LFD. Intake of high FODMAP foods, energy, macronutrients, micronutrients, food groups, and ultra-processed foods were determined.

KEY RESULTS: Median age of participants was 11 years, and 19/31 (61%) were female. Twenty-eight (90%) decreased high FODMAP food intake on the LFD: …

Liver Disease In Aboriginal And Torres Strait Islander People, Yasmina Tashkent, John K. Olynyk, Alan J. Wigg

Journal of the Australian Indigenous HealthInfoNet

Aboriginal and Torres Strait Islander people have a substantially higher prevalence of liver disease than non-Indigenous Australians. Cirrhosis and its complications were the sixth leading cause of mortality for Aboriginal and Torres Strait Islander people in 2020. Liver disease has been estimated to be the third leading cause of the mortality gap between Aboriginal and Torres Strait Islander and non-Indigenous people due to chronic disease, accounting for 11% of this gap. While current trends show reducing mortality rates for Aboriginal and Torres Strait Islander people for conditions including circulatory disease, diabetes and kidney disease, there are no data to suggest …

Xpert Mtb/Rif Ultra Assay For Tuberculosis Disease And Rifampicin Resistance In Children, Alexander W Kay, Tara Ness, Sabine E Verkuijl, Kerri Viney, Annemieke Brands, Tiziana Masini, Lucia González Fernández, Michael Eisenhut, Anne K Detjen, Anna M Mandalakas, Karen R Steingart, Yemisi Takwoingi

Faculty, Staff and Students Publications

BACKGROUND: Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects Mycobacterium tuberculosis complex and rifampicin resistance. We previously published a Cochrane Review 'Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for tuberculosis disease and rifampicin resistance in children'. The current review updates evidence on the diagnostic accuracy of Xpert Ultra in children presumed to have tuberculosis disease. Parts of this review update informed the 2022 WHO updated guidance on management of …

Preoperative Inflammatory Markers As Prognostic Predictors After Hepatocellular Carcinoma Resection: Data From A Western Referral Center, João Paulo Maciel Silva, Fabricio Ferreira Coelho, Alex Jones Flores Cassenote, Vagner Birk Jeismann, Gilton Marques Fonseca, Jaime Arthur Pirola Kruger, José Donizeti De Meira Júnior, Sérgio Carlos Nahas, Paulo Herman

Faculty, Staff and Student Publications

BACKGROUND: Recent studies from eastern centers have demonstrate an association between inflammatory response and long-term outcomes after hepatocellular carcinoma (HCC) resection. However, the prognostic impact of inflammatory markers in western patients, with distinct tumor and epidemiologic features, is still unknown.

AIM: To evaluate the prognostic impact of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), as well as their impact according to tumor size (< 5 cm, 5-10 cm, > 10 cm) in patients undergoing HCC resection with curative intent.

METHODS: Optimal cut-off values for NLR, PLR, and MLR were determined by plotting the receiver operator curves. Overall survival (OS) and disease-free …

Patient-Specific Genome-Scale Metabolic Models For Individualized Predictions Of Liver Disease, Alexandra Manchel, Jan B. Hoek, Ramon Bataller, Radhakrishnan Mahadevan, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The prevalence of liver disease is steadily increasing, coupled with the limited availability of therapeutic treatments. Recent literature points to metabolic reprogramming as a key feature of liver failure. Hence, we sought to uncover the metabolic pathways and mechanisms associated with liver disease and acute liver failure. We generated patient-specific genome scale metabolic models by integrating RNA-seq data from patient liver samples with a generalized human metabolic model. Flux balance analysis simulations showed a distinct separation of non-alcohol associated and alcohol-associated disease states. Our analysis suggests that the alcohol associated liver has an increased flux through nucleotide and glycerophospholipid metabolic …

A Quality Improvement Initiative To Decrease Time To Analgesia In Patients With Sickle Cell And Vaso-Occlusive Crisis: A Population With Disparities In Treatment, Tyler Arnold, R Lane Coffee, Leon Rosenberg, Seethal A Jacob, Sean Thompson, Heather Saavedra, Stephen John Cico, Brian Wagers

Faculty, Staff and Student Publications

INTRODUCTION: Vaso-occlusive crises (VOCs) are the leading cause of emergency department (ED) visits and hospitalizations in patients with sickle cell disease (SCD). Timely administration of analgesia, within 60 minutes of patient registration, is the standard of care for SCD patients with VOCs. Patients with VOCs have longer times to initial analgesia compared to similar painful conditions. The primary aim of the project is to have 75% of patients with VOCs receive initial analgesia within 60 minutes of being registered, the current recommended time frame from the National Heart, Lung, and Blood Institute (NHLBI).

METHODS: A multi-disciplinary team used quality improvement …

Hepatic Circadian And Differentiation Factors Control Liver Susceptibility For Fatty Liver Disease And Tumorigenesis, Baharan Fekry, Aleix Ribas-Latre, Rachel Van Drunen, Rafael Bravo Santos, Samay Shivshankar, Yulin Dai, Zhongming Zhao, Seung-Hee Yoo, Zheng Chen, Kai Sun, Frances M Sladek, Mamoun Younes, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths, and the most common primary liver malignancy to present in the clinic. With the exception of liver transplant, treatment options for advanced HCC are limited, but improved tumor stratification could open the door to new treatment options. Previously, we demonstrated that the circadian regulator Aryl Hydrocarbon-Like Receptor Like 1 (ARNTL, or Bmal1) and the liver-enriched nuclear factor 4 alpha (HNF4α) are robustly co-expressed in healthy liver but incompatible in the context of HCC. Faulty circadian expression of HNF4α- either by isoform switching, or loss of expression- results in an increased …

New Sedatives And Analgesic Drugs For Gastrointestinal Endoscopic Procedures, Jae Min Lee, Yehyun Park, Jin Myung Park, Hong Jun Park, Jun Yong Bae, Seung Young Seo, Jee Hyun Lee, Hyung Ku Chon, Jun-Won Chung, Hyun Ho Choi, Jun Kyu Lee, Byung-Wook Kim

Faculty, Staff and Student Publications

Procedural sedation has become increasingly common in endoscopy. Sedatives and analgesics induce anxiolysis and amnesia. In addition, an appropriate level of sedation is necessary for safe procedures including therapeutic endoscopy. Midazolam and propofol are the most commonly used drugs in sedative endoscopy. In recent years, the need to ascertain the safety and effectiveness of sedation has increased in practice. Therefore, new sedatives and analgesic drugs for optimal sedative endoscopy, have recently emerged. This article reviews the characteristics of sedatives and analgesics, and describes their clinical use in gastrointestinal endoscopy.

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 …

Dietary Fat Composition Shapes Bile Acid Metabolism And Severity Of Liver Injury In A Pig Model Of Pediatric Nafld, Rodrigo Manjarín, Kayla Dillard, Morgan Coffin, Gabriella V Hernandez, Victoria A Smith, Trista Noland-Lidell, Tanvi R Gehani, Hayden J Smart, Kevin Wheeler, Kimberly A Sprayberry, Mark S Edwards, Rob K Fanter, Hunter Glanz, Chad Immoos, Tasha M Santiago-Rodriguez, Jason M Blank, Douglas G Burrin, Brian D Piccolo, Mohammed Abo-Ismail, Michael R La Frano, Magdalena Maj

Faculty, Staff and Students Publications

The objective of this study was to investigate the effect of dietary fatty acid (FA) composition on bile acid (BA) metabolism in a pig model of NAFLD, by using a multiomics approach combined with histology and serum biochemistry. Thirty 20-day-old Iberian pigs pair-housed in pens were randomly assigned to receive 1 of 3 hypercaloric diets for 10 wk: 1) lard-enriched (LAR; n = 5 pens), 2) olive oil-enriched (OLI; n = 5), and 3) coconut oil-enriched (COC; n = 5). Animals were euthanized on week 10 after blood sampling, and liver, colon, and distal ileum (DI) were …

Risk Score Using Demographic And Clinical Risk Factors Predicts Gastric Intestinal Metaplasia Risk In A Us Population, Mimi C Tan, Quynh Ho, Theresa H Nguyen, Yan Liu, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND/AIMS: Screening for gastric intestinal metaplasia (GIM) may lead to early gastric cancer detection. We developed and validated a pre-endoscopy risk prediction model for detection of GIM based on patient-level risk factors in a U.S.

METHODS: We used data from 423 GIM cases and 1796 controls from a cross-sectional study among primary care and endoscopy clinic patients at the Houston VA. We developed the model using backwards stepwise regression and assessed discrimination using area under the receiver operating characteristic (AUROC). The model was internally validated using cross-validation and bootstrapping. The final expanded model was compared to a model including H. …

Virtual Global Health In Graduate Medical Education: A Systematic Review, Lisa Umphrey, Nora Lenhard, Suet Kam Lam, Nathaniel E Hayward, Shaina Hecht, Priya Agrawal, Amy Chambliss, Jessica Evert, Heather Haq, Stephanie M Lauden, George Paasi, Mary Schleicher, Megan Song Mchenry

Faculty, Staff and Students Publications

OBJECTIVES: To synthesize recent virtual global health education activities for graduate medical trainees, document gaps in the literature, suggest future study, and inform best practice recommendations for global health educators.

METHODS: We systematically reviewed articles published on virtual global health education activities from 2012-2021 by searching MEDLINE, EMBASE, Cochrane Library, ERIC, Scopus, Web of Science, and ProQuest Dissertations & Theses A&I. We performed bibliography review and search of conference and organization websites. We included articles about primarily virtual activities targeting for health professional trainees. We collected and qualitatively analyzed descriptive data about activity type, evaluation, audience, and drivers or barriers. …

A Case Series Of Children With Acute Hepatitis And Human Adenovirus Infection, L Helena Gutierrez Sanchez, Henry Shiau, Julia M Baker, Stephanie Saaybi, Markus Buchfellner, William Britt, Veronica Sanchez, Jennifer L Potter, L Amanda Ingram, David Kelly, Xiaoyan Lu, Stephanie Ayers-Millsap, Wesley G Willeford, Negar Rassaei, Julu Bhatnagar, Hannah Bullock, Sarah Reagan-Steiner, Ali Martin, Michael E Rogers, Anna M Banc-Husu, Sanjiv Harpavat, Daniel H Leung, Elizabeth A Moulton, Daryl M Lamson, Kirsten St George, Aron J Hall, Umesh Parashar, Adam Macneil, Jacqueline E Tate, Hannah L Kirking

Faculty, Staff and Students Publications

BACKGROUND: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia.

METHODS: We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children’s of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing.

RESULTS: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 …

Targeting Hyaluronic Acid Synthase-3 (Has3) For The Treatment Of Advanced Renal Cell Carcinoma, Xiaohan Xu, Kyle L Poulsen, Lijuan Wu, Shan Liu, Tatsunori Miyata, Qiaoling Song, Qingda Wei, Chenyang Zhao, Chunhua Lin, Jinbo Yang

Faculty, Staff and Student Publications

Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form of NAFL, can be progressive and more susceptible to developing cirrhosis and hepatocellular carcinoma. Currently, lifestyle interventions are the most essential and effective strategies for preventing and controlling NAFL without the development of fibrosis. While there are still limited appropriate drugs specifically to treat NAFL/NASH, growing progress is being seen in elucidating the pathogenesis and identifying therapeutic targets. In this review, we discussed recent developments in etiology and prospective therapeutic targets, as well as pharmacological candidates in pre/clinical trials and patents, with a …

A Differential Diagnosis Of Unusual Gastric Ulcer, Soo-Yoon Sung, Hyun Ho Choi, Kyung Jin Seo

Faculty, Staff and Student Publications

The endoscopic findings of diffuse large B cell lymphoma have various presentations. In our case, the patient had developed multiple elevated central ulceration lesions, and the peripheral elevated portion had a heaped-up margin. The margin had a sharp, smooth edge that was not infiltrative and could be confused with a simple gastric ulcer. Endoscopists should be aware of the possibility of multiple lymphoma ulcers with heaped-up margins. We present some unusual endoscopic features of lymphoma, which are easily misdiagnosed as gastric ulcers.

Hepatic Recruitment Of Eosinophils And Their Protective Function During Acute Liver Injury, Long Xu, Yang Yang, Yankai Wen, Jong-Min Jeong, Christoph Emontzpohl, Constance L Atkins, Zhaoli Sun, Kyle L Poulsen, David R Hall, J Steve Bynon, Bin Gao, William M Lee, Jody Rule, Elizabeth A Jacobsen, Hua Wang, Cynthia Ju

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Beyond the classical description of eosinophil functions in parasite infections and allergic diseases, emerging evidence supports a critical role of eosinophils in resolving inflammation and promoting tissue remodeling. However, the role of eosinophils in liver injury and the underlying mechanism of their recruitment into the liver remain unclear.

METHODS: Hepatic eosinophils were detected and quantified using flow cytometry and immunohistochemical staining. Eosinophil-deficient (ΔdblGata1) mice were used to investigate the role of eosinophils in 3 models of acute liver injury. In vivo experiments using Il33

RESULTS: Hepatic accumulation of eosinophils was observed in patients with acetaminophen (APAP)-induced liver …

Mir-103-3p Promotes Hepatic Steatosis To Aggravate Nonalcoholic Fatty Liver Disease By Targeting Of Acox1, Jiexia Ding, Caixia Xia, Panpan Cen, Siying Li, Lifei Yu, Jing Zhu, Jie Jin

Faculty, Staff and Student Publications

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major risk factor for hepatocellular carcinoma, and alterations in miRNA expression are related to the development of NAFLD. However, the role of miRNAs in regulating the development of NAFLD is still poorly understood.

METHODS: We used qRT-PCR to detect the level of miR-103-3p in both cell and mouse models of NAFLD. Biochemical assays, DCF-DA assays, Oil red O staining and HE staining were used to detect the role of miR-103-3p in NAFLD development. Target genes of miR-103-3p were predicted using the TargetScan database and verified by qRT-PCR, western blot and dual-luciferase assays. …

Randomized Placebo-Controlled Trial Of Losartan For Pediatric Nafld, Miriam B Vos, Mark L Van Natta, Niviann M Blondet, Srinivasan Dasarathy, Mark Fishbein, Paula Hertel, Ajay K Jain, Saul J Karpen, Joel E Lavine, Saeed Mohammad, Laura A Miriel, Jean P Molleston, Marialena Mouzaki, Arun Sanyal, Emily P Sharkey, Jeffrey B Schwimmer, James Tonascia, Laura A Wilson, Stavra A Xanthakos, Nash Clinical Research Network

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects.

APPROACH AND RESULTS: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020). Inclusion criteria were age 8-17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT …

Clinical Factors Associated With Non-Obese Nonalcoholic Fatty Liver Disease Detected Among Us Adults In The Nhanes 2017-2018, Zayd Adnan Razouki, Xiaotao Zhang, Jessica P Hwang, Natalia I Heredia

Faculty, Staff and Student Publications

NAFLD can occur in non-obese individuals with BMI < 25 kg/m2. Our goal was to examine the prevalence and clinical factors associated with non-obese NAFLD using vibration-controlled transient elastography (VCTE) with controlled attenuation parameter which estimates steatosis and fibrosis among US adults. We aggregated data from the 2017−2018 cycle of NHANES and included adults (age ≥ 20 years) with BMI < 25 kg/m2 with complete data for the survey, medical examination, and VCTE along with controlled attenuation parameter (CAP). We excluded participants with risks of other liver diseases. We considered patients to have non-obese NAFLD if CAP was >285 dB/m, or non-obese NAFLD fibrosis if this CAP criteria was met and liver stiffness was >8.6 kPa. We calculated the adjusted OR and 95% CI for associations with non-obese NAFLD using multivariable logistic regression. The prevalence of non-obese NAFLD was 6.2% and Asian Americans (12.2%) had the highest non-obese NAFLD prevalence. Clinical factors associated with non-obese NAFLD were advanced age and metabolic syndrome (ORadjusted = 6.8, 95% CI 3.0−15.5). In a separate model, we found elevated glucose (ORadjusted = 4.1, 95% CI 2.1−7.9), triglycerides (ORadjusted = 3.8, 95% CI 1.7−8.5), and …