Hepatology Commons^™

Molecular Pathway Dysregulation In Chronic Liver Disease: Metabolic And Mechanotransductive Drivers Of Hepatic Pathophysiology, Samantha Harvat

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

Metabolic dysfunction–associated steatotic liver disease (MASLD) represents a rapidly growing cause of chronic liver injury, yet the molecular interactions linking metabolic stress, inflammation, fibrosis, and hepatocellular carcinoma (HCC) remain incompletely defined. This thesis integrates transcriptomic analyses across multiple GEO datasets to identify coordinated metabolic, inflammatory, and mechanotransductive pathways that collectively drive disease progression.

Analysis of human liver biopsy datasets (GSE126848 and GSE89632) revealed consistent suppression of glycolysis, β-oxidation, and oxidative phosphorylation across MASLD and MASH samples, accompanied by modest compensatory TCA cycle activation. These alterations reflect impaired metabolic flexibility, mitochondrial stress, and increased ROS susceptibility. Concurrently, cytokine-network enrichment demonstrated activation …

Cholestasis And Fluid Flow Are Biomechanic Regulators Of Cholangiocarcinoma Progression, Andrew Oleksijew

Theses & Dissertations

Cholestasis, altered or absent bile flow, is associated with poor survival in patients with cholangiocarcinoma, an aggressive cancer of the biliary epithelium. Changes in bile flow often result in stricture or obstruction. Experimental cholestasis promoted tumor growth and progression. However, studies are needed that directly assess the mechanical interaction between bile flow, or bile shear stress, and cholangiocarcinoma signaling. We hypothesized that cholestasis and absent bile shear stress activated cancer signaling and increased aggressive cellular behaviors such as proliferation and migration. Fluid shear stress approximating bile flow was applied by orbital culture plate method and compared to identical static culture …

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 …

Turmeric-Associated Liver Injury: A Rare Case Of Drug-Induced Liver Injury, David N Smith, Prisca Pungwe, Lauren L Comer, Teminioluwa A Ajayi, Milena G Suarez

Faculty, Staff and Students Publications

Turmeric is popularly used as a naturopathic supplement associated with myriad benefits and has long been generally regarded as safe. However, increasing reports of turmeric-associated liver injury have emerged over recent years. This case presents a female patient without significant past medical history who presents with signs and symptoms of acute hepatitis after consuming a turmeric-containing tea. Her case adds to a growing body of evidence that dosage safety, manufacturing, and pharmacologic delivery practices for turmeric supplements should be investigated.

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 …

Perceptions Of Weight Status And Energy Balance Behaviors Among Patients With Non-Alcoholic Fatty Liver Disease, Natalia I Heredia, Ruchi Gaba, Yan Liu, Shilpa Jain, Manasi Rungta, Manav Rungta, Hashem B El-Serag, Fasiha Kanwal, Aaron P Thrift, Maya Balakrishnan

Faculty, Staff and Students Publications

Weight loss through behavioral modification is central to treating non-alcoholic fatty liver disease (NAFLD). To achieve this, patients need to accurately self-perceive their health behaviors. We aimed to identify predictors of concordance between self-perception and objective measures of body weight, physical activity (PA) and dietary behaviors. We used data from the Harris County NAFLD Cohort, an ongoing prospective study in a regional safety-net healthcare system. Patients completed self-administered baseline questionnaires on demographics, diet, PA, and self-perceptions. We assessed concordance between actual and self-perceived body weight and energy-balance behaviors. Multivariable logistic regression identified predictors of concordance. Patients (n = 458; average …

Comparative Performance Of Risk Prediction Models For Hepatitis B-Related Hepatocellular Carcinoma In The United States, Hyun-Seok Kim, Xian Yu, Jennifer Kramer, Aaron P Thrift, Pete Richardson, Yao-Chun Hsu, Avegail Flores, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Guidelines recommend hepatocellular carcinoma (HCC) surveillance in patients with chronic HBV infection. Several HCC risk prediction models are available to guide surveillance decisions, but their comparative performance remains unclear.

METHODS: Using a retrospective cohort of patients with HBV treated with nucleos(t)ide analogues at 130 Veterans Administration facilities between 9/1/2008 and 12/31/2018, we calculated risk scores from 10 HCC risk prediction models (REACH-B, PAGE-B, m-PAGE-B, CU-HCC, HCC-RESCUE, CAMD, APA-B, REAL-B, AASL-HCC, RWS-HCC). We estimated the models' discrimination and calibration. We calculated HCC incidence in risk categories defined by the reported cut-offs for all models.

RESULTS: Of 3,101 patients …

Advantage Of 16s Rrna Amplicon Sequencing In Helicobacter Pylori Diagnosis, Boldbaatar Gantuya, Hashem B El Serag, Batsaikhan Saruuljavkhlan, Dashdorj Azzaya, Takashi Matsumoto, Tomohisa Uchida, Khasag Oyuntsetseg, Nyamdorj Oyunbileg, Duger Davaadorj, Yoshio Yamaoka

Faculty, Staff and Students Publications

BACKGROUND: 16S rRNA amplicon sequencing is an accurate method of detecting microbial infection without culture. It is unclear if sequencing has additional benefits over routine diagnostic methods for Helicobacter pylori testing.

METHODS: We enrolled Mongolian volunteers with dyspepsia. Using routine diagnostic methods, positive H. pylori was defined as positive results on histology/immunohistochemistry, culture, rapid urease test, or serology; negative H. pylori was defined by negative results from all these tests. We performed 16S rRNA sequencing on gastric biopsy specimens and calculated cutoffs for operational taxonomic units (OTUs) and relative abundance (RA) to define positive results using ROC curves.

RESULTS: We …

A Novel Biomarker Panel For The Early Detection And Risk Assessment Of Hepatocellular Carcinoma In Patients With Cirrhosis, Ilvira M Khan, Donjeta Gjuka, Jingjing Jiao, Xiaoling Song, Ying Wang, Jing Wang, Peng Wei, Hashem B El-Serag, Jorge A Marrero, Laura Beretta

Faculty, Staff and Students Publications

Novel biomarkers for hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis are urgently needed. We previously identified osteopontin (OPN) as a promising biomarker for the early detection of HCC. This study is to further validate the performance of OPN and identify fatty acids (FA) that could improve OPN's performance in HCC risk assessment in patients with cirrhosis. To that end, we selected 103 patients with cirrhosis under surveillance. Among them, 40 patients developed HCC during follow-up. We investigated in these 103 patients, the association between HCC incidence and prediagnostic serum levels of AFP, OPN, and 46 FAs. OPN performance was …

Prevalence Of Barrett’S Esophagus And Performance Of Societal Screening Guidelines In An Unreferred Primary Care Population Of Us Veterans, Theresa H Nguyen, Aaron P Thrift, Massimo Rugge, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Less than 10% of patients diagnosed with esophageal adenocarcinoma have a pre-existing Barrett's esophagus (BE) diagnosis, possibly because of suboptimal performance of guidelines. We examined the prevalence of BE in a previously unscreened primary care population and the potential yield of practice BE screening guidelines.

METHODS: This was a retrospective analysis of a prospective cross-sectional study of consecutively recruited unreferred patients from primary care clinics who underwent study upper endoscopy. We examined the performance of BE screening guidelines of the European Society of Gastrointestinal Endoscopy (ESGE), British Society of Gastroenterology (BSG), American Society for Gastrointestinal Endoscopy (ASGE), …

Prevalence Of Gastric Intestinal Metaplasia In A Multiethnic Us Veterans Population, Theresa H Nguyen, Mimi C Tan, Yan Liu, Massimo Rugge, Aaron P Thrift, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: There is a need to identify individuals with gastric intestinal metaplasia, a precursor to gastric cancer, so they can be offered screening and surveillance. We examined the prevalence of gastric intestinal metaplasia, detected by upper endoscopy biopsy analysis, in different race and ethnic subgroups. We also investigated the extent to which Helicobacter pylori infection, with or without acute and chronic gastritis, accounts for observed associations between race or ethnicity and risk of gastric intestinal metaplasia.

METHODS: We used data from a cross-sectional study of consecutively recruited patients at the Michael E. DeBakey Veterans Affairs Medical Center in …

Provider Attitudes And Practice Patterns For Direct-Acting Antiviral Therapy For Patients With Hepatocellular Carcinoma, Nicole E Rich, Ju Dong Yang, Ponni V Perumalswami, Naim Alkhouri, Whitney Jackson, Neehar D Parikh, Neil Mehta, Reena Salgia, Andres Duarte-Rojo, Laura Kulik, Mina Rakoski, Adnan Said, Omobonike Oloruntoba, George N Ioannou, Maarouf A Hoteit, Andrew M Moon, Amol S Rangnekar, Sheila L Eswaran, Elizabeth Zheng, Janice H Jou, James Hanje, Anjana Pillai, Ruben Hernaez, Robert Wong, Steven Scaglione, Hrishikesh Samant, Devika Kapuria, Shaun Chandna, Russell Rosenblatt, Veeral Ajmera, Catherine T Frenette, Sanjaya K Satapathy, Parvez Mantry, Prasun Jalal, Binu V John, Oren K Fix, Michael Leise, Christina C Lindenmeyer, Avegail Flores, Nayan Patel, Z Gordon Jiang, Nyan Latt, Renumathy Dhanasekaran, Mobolaji Odewole, Sofia Kagan, Jorge A Marrero, Amit G Singal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are effective against hepatitis C virus and sustained virologic response is associated with reduced incidence of hepatocellular carcinoma (HCC). However, there is controversy over the use of DAAs in patients with active or treated HCC and uncertainty about optimal management of these patients. We aimed to characterize attitudes and practice patterns of hepatology practitioners in the United States regarding the use of DAAs in patients with HCC.

METHODS: We conducted a survey of hepatology providers at 47 tertiary care centers in 25 states. Surveys were sent to 476 providers and we received 279 responses …

Protective Role Of Dietary Curcumin In The Prevention Of The Oxidative Stress Induced By Chronic Alcohol With Respect To Hepatic Injury And Antiatherogenic Markers, Ravi Varatharajalu, Mamatha Garige, Leslie C Leckey, Karina Reyes-Gordillo, Ruchi Shah, M. Raj Lakshman

Biochemistry and Molecular Medicine Faculty Publications

No abstract provided.

Localization And Expression Level Of Vascular Endothelial Growth Factor After Partial Hepatectomy Of Wky Rats, Adam Kronebusch, Tyler Koonst

Undergraduate Research Symposium

Inflammation and fibrosis are indicative of liver regeneration following injury and chronic liver diseases, such as cirrhosis and hepatocellular carcinoma. The formation of new vasculature via the process of angiogenesis is vital to the pathological progression of liver regeneration and these diseases. Thus, inhibiting the process of angiogenesis could have the potential to stop or slow the progression of chronic liver diseases. Vascular endothelial growth factor (VEGF) is the most potent and specific growth factor for initiating the process of angiogenesis, making it a prime target to inhibit angiogenesis. Bevacizumab is an antibody that binds to VEGF, inhibiting it from …

Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof

Dissertations and Theses (Open Access)

Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage …

The Role Of Protein Kinase C Epsilon In Hydrogen Peroxide And Nitric Oxide Release During Oxidative Stress Caused By Extracorporeal Shockwave Lithotripsy, Edward S. Iames

PCOM Biomedical Studies Student Scholarship

Clinical extracorporeal shock wave lithotripsy (ESWL) treatment to ablate kidney stones can cause acute damage to the renal microvasculature. Accumulation of continued treatment with shockwave therapy can lead to chronic damage to the kidney, and lead to clinical hypertension. Shockwaves have been shown to stimulate endothelial cells to release superoxide (SO), which is converted to hydrogen peroxide (H₂O₂), and reacts with nitric oxide (NO) to produce peroxynitrite anion (OONO^-), creating a powerful oxidant that increases oxidative stress while simultaneously reducing NO bioavailability. Increased oxidative stress during events such as ESWL, also uncouples NO production …