Hepatology Commons^™

The Autophagic Protein P62 Is A Target Of Reactive Aldehydes In Human And Murine Cholestatic Liver Disease, Colin T Shearn, Aimee L Anderson, Michael W Devereux, David J Orlicky, Cole Michel, Dennis R Petersen, Colin G Miller, Sanjiv Harpavat, Edward E Schmidt, Ronald J Sokol

Faculty, Staff and Students Publications

Inflammatory cholestatic liver diseases, including Primary Sclerosing Cholangitis (PSC), are characterized by periportal inflammation with progression to cirrhosis. The objective of this study was to examine interactions between oxidative stress and autophagy in cholestasis. Using hepatic tissue from male acute cholestatic (bile duct ligated) as well as chronic cholestatic (Mdr2KO) mice, localization of oxidative stress, the antioxidant response and induction of autophagy were analyzed and compared to human PSC liver. Concurrently, the ability of reactive aldehydes to post-translationally modify the autophagosome marker p62 was assessed in PSC liver tissue and in cell culture. Expression of autophagy markers was upregulated in …

Pathologic Inflammation In Malnutrition Is Driven By Proinflammatory Intestinal Microbiota, Large Intestine Barrier Dysfunction, And Translocation Of Bacterial Lipopolysaccharide, Grace T Patterson, Elvia Y Osorio, Alex Peniche, Sara M Dann, Erika Cordova, Geoffrey A Preidis, Ji Ho Suh, Ichiaki Ito, Omar A Saldarriaga, Michael Loeffelholz, Nadim J Ajami, Bruno L Travi, Peter C Melby

Faculty, Staff and Students Publications

Acute malnutrition, or wasting, is implicated in over half of all deaths in children under five and increases risk of infectious disease. Studies in humans and preclinical models have demonstrated that malnutrition is linked to an immature intestinal microbiota characterized by increased prevalence of Enterobacteriaceae. Observational studies in children with moderate acute malnutrition (MAM) have also observed heightened systemic inflammation and increased circulating bacterial lipopolysaccharides (LPS; endotoxin). However, the mechanisms that underpin the systemic inflammatory state and endotoxemia, and their pathophysiological consequences, remain uncertain. Understanding these pathophysiological mechanisms is necessary to design targeted treatments that will improve the unacceptable rate …

Hepatic Pparα Is Destabilized By Sirt1 Deacetylase In Undernourished Male Mice, Ji Ho Suh, Kang Ho Kim, Margaret E Conner, David D Moore, Geoffrey A Preidis

Faculty, Staff and Students Publications

The nutrient sensing nuclear receptor peroxisome proliferator-activated receptor-α (PPARα) regulates the host response to short-term fasting by inducing hepatic transcriptional programming of ketogenesis, fatty acid oxidation and transport, and autophagy. This adaptation is ineffective in chronically undernourished individuals, among whom dyslipidemia and hepatic steatosis are common. We recently reported that hepatic PPARα protein is profoundly depleted in male mice undernourished by a low-protein, low-fat diet. Here, we identify PPARα as a deacetylation target of the NAD-dependent deacetylase sirtuin-1 (SIRT1) and link this to the decrease in PPARα protein levels in undernourished liver. Livers from undernourished male mice expressed high levels …

The Texas Collaborative Center For Hepatocellular Cancer: Reducing Liver Cancer Mortality In Texas Through Coordination, Collaboration And Advocacy, Ariel C Harrison, Fasiha Kanwal, Sumeet K Asrani, Aaron P Thrift, Chris I Amos, Maria L Jibaja-Weiss, Jane R Montealegre, Jessica P Hwang, Amit G Singal, Hashem B El-Serag

Faculty, Staff and Students Publications

Texas has the highest age-adjusted incidence rate of hepatocellular carcinoma (HCC) in the United States. To address cancer prevention and early detection through research, Cancer Prevention and Research Institute of Texas (CPRIT) has funded the Texas Collaborative Center for Hepatocellular Cancer (TeCH) to facilitate liver cancer research, education and advocacy activities. This paper describes the organizational structure, program measures, the actions completed and future plans of TeCH. This center is comprised of several cores and committees including the Administrative Core, Steering Committee, Data and Biospecimen Core, Scientific Committee, Clinical Network Committee, and the Community Outreach Committee. Each core and committee …

Clinical Outcome And Gut Development After Insulin-Like Growth Factor-1 Supplementation To Preterm Pigs, Kristine Holgersen, Martin Bo Rasmussen, Galen Carey, Douglas G Burrin, Thomas Thymann, Per Torp Sangild

Faculty, Staff and Students Publications

BACKGROUND: Elevation of circulating insulin-like growth factor-1 (IGF-1) within normal physiological levels may alleviate several morbidities in preterm infants but safety and efficacy remain unclear. We hypothesized that IGF-1 supplementation during the first 1-2 weeks after preterm birth improves clinical outcomes and gut development, using preterm pigs as a model for infants.

METHODS: Preterm pigs were given vehicle or recombinant human IGF-1/binding protein-3 (rhIGF-1, 2.25 mg/kg/d) by subcutaneous injections for 8 days (Experiment 1, n = 34), or by systemic infusion for 4 days (Experiment 2, n = 19), before collection of blood and organs for analyses.

RESULTS: In both …

De Novo Glycine Synthesis Is Reduced In Adults With Morbid Obesity And Increases Following Bariatric Surgery, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Vieon Wu, Chun Fan Lee, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

BACKGROUND: Glycine is a dietary non-essential amino acid that is low in obesity and increases following bariatric surgery. However, the exact mechanism responsible remains unclear and it is unknown whether hypoglycinemia is a cause or consequence of insulin resistance.

OBJECTIVE: Using multiple isotopically labeled tracers, we aimed to determine the underlying kinetic changes responsible for hypoglycinemia in obesity by: 1) Comparing glycine kinetics between participants with morbid obesity (BMI ≥ 32.5 kg/m

METHODS: [1,2-

RESULTS: Compared to controls, participants with morbid obesity had significantly lower plasma glycine concentrations at 163 (153-171) vs. 201 (172-227) µmol/L and significantly reduced

CONCLUSION: Hypoglycinemia …

Interaction Between Alcohol Consumption And Pnpla3 Variant In The Prevalence Of Hepatic Steatosis In The Us Population, Mariana Lazo, Usama Bilal, Mack C Mitchell, James Potter, Ruben Hernaez, Jeanne M Clark

Faculty, Staff and Students Publications

BACKGROUND & AIMS: To our knowledge, the interaction between alcohol consumption and PNPLA3 genotype on hepatic steatosis has not been explored in a representative sample. To examine the interaction between alcohol consumption and PNPLA3 genotype on hepatic steatosis in the US adult population.

METHODS: Cross-sectional study of 4,674 adult participants of the Third National Health and Nutrition Examination Survey, Phase 2 (1991-1994) with data on PNPLA3 genotype, self-reported alcohol consumption, ultrasound-defined hepatic steatosis and socio-demographic characteristics.

RESULTS: In 1991-1994 in the U.S. population, the weighted allele frequency of the G (risk) allele of the rs738409 at PNPLA3 was 25.4%. We …

Early Antibiotic Exposure Is Not Detrimental To Therapeutic Effect From Immunotherapy In Hepatocellular Carcinoma, Petros Fessas, Muntaha Naeem, Matthias Pinter, Thomas U Marron, David Szafron, Lorenz Balcar, Anwaar Saeed, Tomi Jun, Sirish Dharmapuri, Anuhya Gampa, Yinghong Wang, Uqba Khan, Mahvish Muzaffar, Musharraf Navaid, Pei-Chang Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Hannah Hildebrand, Yehia I Abugabal, Tiziana Pressiani, Nicola Personeni, Naoshi Nishida, Masatoshi Kudo, Ahmed Kaseb, Yi-Hsiang Huang, Celina Ang, Anjana Pillai, Lorenza Rimassa, Abdul Rafeh Naqash, Elad Sharon, Alessio Cortellini, David J Pinato

Faculty, Staff and Students Publications

BACKGROUND AND RATIONALE: Immune checkpoint inhibitor (ICI) therapy is an expanding therapeutic option for hepatocellular carcinoma (HCC). Antibiotics (ATB) taken prior to or early during ICI therapy can impact immunotherapy efficacy across indications; however, the effect of ATB is undefined in HCC.

METHODS: In a large international cohort of 450 ICI recipients from Europe, North America, and Asia, we categorized patients according to timing of ATB focusing on exposure within -30 to +30 days from ICI (early immunotherapy period [EIOP]). EIOP was evaluated in association with overall survival (OS), progression-free survival (PFS), and best radiologic response using RECIST 1.1 criteria. …

Substance Abuse Relapse Is Not About Willpower But Is The Culmination Of Psychological And Socioeconomic Stress, Paul A. Steffes

Clinical Research in Practice: The Journal of Team Hippocrates

The author reflects on the impact of non-judgmental listening on patient care outcomes.

Activation Of The Innate Immune System In Children With Irritable Bowel Syndrome Evidenced By Increased Fecal Human Β-Defensin-2, Robert J Shulman, Sridevi Devaraj, Margaret Heitkemper

Children’s Nutrition Research Center Staff Publications

Background & aims: The role of the innate immune system in functional gastrointestinal pain disorders is unclear. We investigated the role of β-defensin-2 and gut permeability in childhood irritable bowel syndrome (IBS) and functional abdominal pain (FAP) symptom generation.

Methods: Fecal β-defensin-2 (and in a subset, gut permeability) was measured in children with IBS (n = 116), FAP (n = 33), and healthy control (HC) children (n = 72). IBS and FAP patients were recruited from tertiary and primary care, and HCs were recruited from primary care.

Results: β-defensin-2 concentration was greater in children with IBS (P = .003) and …

Outcomes Of Primary Versus Revisional Robotically Assisted Laparoscopic Roux-En-Y Gastric Bypass: A Multicenter Analysis Of Ten-Year Experience, Pouya Iranmanesh, John Fam, Thomas Nguyen, David Talarico, Kavita D Chandwani, Kulvinder S Bajwa, Melissa M Felinski, Leon V Katz, Sheilendra S Mehta, Stephan R Myers, Brad E Snyder, Peter A Walker, Todd D Wilson, Angielyn R Rivera, Connie L Klein, Shinil K Shah, Erik B Wilson

Faculty, Staff and Student Publications

BACKGROUND: Postoperative morbidity after laparoscopic bariatric surgery is considered higher for patients undergoing revisional versus primary procedures. The objective of this retrospective cohort study was to compare outcomes between patients undergoing primary versus revisional robotically assisted laparoscopic (RAL) Roux-en-Y gastric bypass (RYGB).

METHODS: Data of all patients who underwent RAL primary and revisional RYGB between 2009 and 2019 at two accredited, high-volume bariatric surgery centers-the Memorial Hermann - Texas Medical Center, Houston, TX, and the Tower Health, Reading Hospital, Reading, PA, were analyzed. Primary outcomes were early (< 30 days) and overall postoperative complications. Secondary outcomes included intraoperative complications, operative times, conversions to laparotomy, length of hospital stay, early (< 30 days) postoperative readmissions and deaths.

RESULTS: Data of 1072 patients were analyzed, including 806 primary and 266 …

Use Of Human Tissue Stem Cell-Derived Organoid Cultures To Model Enterohepatic Circulation, Sarah E Blutt, Sue E Crawford, Carolyn Bomidi, Xi-Lei Zeng, James R Broughman, Matthew Robertson, Cristian Coarfa, Mary Elizabeth M Tessier, Tor Savidge, F Blaine Hollinger, Steven A Curley, Mark Donowitz, Mary K Estes

Faculty, Staff and Students Publications

The use of human tissue stem cell-derived organoids has advanced our knowledge of human physiological and pathophysiological processes that are unable to be studied using other model systems. Increased understanding of human epithelial tissues including intestine, stomach, liver, pancreas, lung, and brain have been achieved using organoids. However, it is not yet clear whether these cultures recapitulate in vivo organ-to-organ signaling or communication. In this work, we demonstrate that mature stem cell-derived intestinal and liver organoid cultures each express functional molecules that modulate bile acid uptake and recycling. These organoid cultures can be physically coupled in a Transwell system and …

Extracorporeal Membrane Oxygenation Rescue For Severe Aspiration Pneumonitis In Two Patients After Roux-En-Y Gastric Bypass Procedure, Melissa M Felinski, Daniyal Abbas, Peter A Walker, John A Primomo, Tanyaradzwa M Kajese, Biswajit Kar, Igor D Gregoric, Igor Banjac, Lisa Janowiak, Sriram Nathan, Rahat Hussain, Sheilendra S Mehta, Kulvinder S Bajwa, Shinil K Shah, Bindu Akkanti

Faculty, Staff and Student Publications

Roux-en-y gastric bypass (RYGB) is one of the most common weight loss surgical procedures performed in the United States. Early post-operative small bowel obstruction is a rare but potentially morbid, complication of RYGB. We report two patients who underwent RYGB and required subsequent treatment for a post-operative small bowel obstruction. Their post-operative course was complicated by severe aspiration pneumonitis leading to hypoxemic respiratory failure requiring rescue with femoral veno-venous extracorporeal membrane oxygenation (V-V ECMO). Both patients were successfully extubated, weaned off V-V ECMO support, and discharged to home. These cases highlight the potential role of V-V ECMO for patients who …

Urinary Bile Acid Indices As Prognostic Biomarkers For The Complications Of Liver Diseases, Wenkuan Li

Theses & Dissertations

Hepatobilary diseases cause the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues, which may lead to an unfavorable prognosis. In this study, we compared the urinary BA profile in 257 patients with hepatobilary diseases during a 7-year follow-up period. We investigated the use of the urinary BA profile to develop logistic regression models to predict the prognosis of hepatobiliary diseases in terms of developing disease-related complications, especially for ascites. The urinary BA profile was characterized by calculating BA indices, which quantify the composition, metabolism, hydrophilicity, and toxicity of the BA profile. All patients had high …

Microbial Science Research In The Post-Covid Environment, Nguyen K Nguyen, Carey-Ann D Burnham, Arturo Casadevall, Mary K Estes, Rebecca V Ferrell, Suzanne M J Fleiszig, Speakers, Moderators, And Panelists Of The Asm Virtual Symposium: Microbial Science Research In The Post-Covid Environment

Faculty, Staff and Students Publications

Since early 2020, the world has witnessed the unprecedented accomplishments of the scientific community in the fight against the coronavirus disease 2019 (COVID-19) pandemic. In the meantime, we also learned valuable lessons and recognized the challenges that hindered our successes. In this article, we synthesize the ideas discussed at the ASM Virtual Symposium: Microbial Science Research in the Post-COVID Environment on 10 November 2020. We propose three new approaches that microbiology researchers can embrace to overcome these challenges. Moreover, we suggest broad systematic changes to focus on social impacts, teamwork, and diversity, equity, and inclusion. We believe these values are …

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 …

Patient-Reported Barriers Are Associated With Receipt Of Hepatocellular Carcinoma Surveillance In A Multicenter Cohort Of Patients With Cirrhosis, Amit G Singal, Jasmin A Tiro, Caitlin C Murphy, James-Michael Blackwell, Jennifer R Kramer, Aisha Khan, Yan Liu, Song Zhang, Jessica L Phillips, Ruben Hernaez

Faculty, Staff and Students Publications

BACKGROUND: More than 20% of patients with cirrhosis do not receive semi-annual hepatocellular carcinoma (HCC) surveillance as recommended. Few studies have evaluated the effects of patient-level factors on surveillance receipt.

METHODS: We administered a telephone survey to a large cohort of patients with cirrhosis from 3 health systems (a tertiary care referral center, a safety-net health system, and Veterans Affairs) to characterize patient knowledge, attitudes, and perceived barriers of HCC surveillance. Multinomial logistic regression was performed to identify factors associated with HCC surveillance receipt (semi-annual and annual vs none) during the 12-month period preceding survey administration.

RESULTS: Of 2871 patients …

Sirt3 Is Required For Liver Regeneration But Not For The Beneficial Effect Of Nicotinamide Riboside, Sarmistha Mukherjee, James Mo, Lauren M Paolella, Caroline E Perry, Jade Toth, Mindy M Hugo, Qingwei Chu, Qiang Tong, Karthikeyani Chellappa, Joseph A Baur

Children’s Nutrition Research Center Staff Publications

Liver regeneration is critical to survival after traumatic injuries, exposure to hepatotoxins, or surgical interventions, yet the underlying signaling and metabolic pathways remain unclear. In this study, we show that hepatocyte-specific loss of the mitochondrial deacetylase SIRT3 drastically impairs regeneration and worsens mitochondrial function after partial hepatectomy. Sirtuins, including SIRT3, require NAD as a cosubstrate. We previously showed that the NAD precursor nicotinamide riboside (NR) promotes liver regeneration, but whether this involves sirtuins has not been tested. Here, we show that despite their NAD dependence and critical roles in regeneration, neither SIRT3 nor its nuclear counterpart SIRT1 is required for …

Primary Effusion Lymphoma: A Clinicopathological Study Of 70 Cases, Zhihong Hu, Zenggang Pan, Weina Chen, Yang Shi, Wei Wang, Ji Yuan, Endi Wang, Shanxiang Zhang, Habibe Kurt, Brenda Mai, Xiaohui Zhang, Hui Liu, Adan A Rios, Hilary Y Ma, Nghia D Nguyen, L Jeffrey Medeiros, Shimin Hu

Faculty, Staff and Student Publications

Primary effusion lymphoma (PEL) is a rare type of large B-cell lymphoma associated with human herpesvirus 8 (HHV8) infection. Patients with PEL usually present with an effusion, but occasionally with an extracavitary mass. In this study, we reported a cohort of 70 patients with PEL: 67 men and 3 women with a median age of 46 years (range 26–91). Of these, 56 (80%) patients had human immunodeficiency virus (HIV) infection, eight were HIV-negative, and six had unknown HIV status. Nineteen (27%) patients had Kaposi sarcoma. Thirty-five (50%) patients presented with effusion only, 27 (39%) had an extracavitary mass or masses …

Vertical Sleeve Gastrectomy Confers Metabolic Improvements By Reducing Intestinal Bile Acids And Lipid Absorption In Mice, Lili Ding, Eryun Zhang, Qiaoling Yang, Lihua Jin, Kyle M Sousa, Bingning Dong, Yangmeng Wang, Jui Tu, Xiaoxiao Ma, Jingyan Tian, Hongli Zhang, Zhipeng Fang, Ana Guan, Yixin Zhang, Zhengtao Wang, David D Moore, Li Yang, Wendong Huang

Faculty, Staff and Students Publications

Vertical sleeve gastrectomy (VSG) is a highly effective bariatric surgery that sustainably treats obesity and type 2 diabetes (T2D). However, the underlying mechanisms governing its metabolic benefits remain unclear. In this study, we have used four different genetically modified mouse lines to understand the link between bile acid circulation and metabolic effects of VSG. Instead of directly activating the nuclear bile acid receptor farnesoid X receptor (Fxr) in the liver or intestine, VSG reduces intestinal levels of bile acids, thereby decreasing fat absorption in the intestine. Given the rising popularity of bariatric surgeries to treat obesity and associated T2D, the …

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 …

Meld-Na Is More Strongly Associated With Risk Of Infection And Outcomes Than Other Characteristics Of Patients With Cirrhosis, Zachary P Fricker, V V Pavan Kedar Mukthinuthalapati, Samuel Akinyeye, Naga Chalasani, Bashar M Attar, Maya Balakrishnan, Marwan Ghabril, Michelle T Long

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: The nature and outcomes of infection among patients with cirrhosis in safety-net hospitals are not well described. We aimed to characterize the rate of and risk factors for infection, both present on admission and nosocomial, in this unique population. We hypothesized that infections would be associated with adverse outcomes such as short-term mortality.

METHODS: We used descriptive statistics to characterize infections within a retrospective cohort characterized previously. We used multivariable logistic regression models to assess potential risk factors for infection and associations with key outcomes such as short-term mortality and length of stay.

RESULTS: The study cohort …

Model For End-Stage Liver Disease-Sodium Underestimates 90-Day Mortality Risk In Patients With Acute-On-Chronic Liver Failure, Ruben Hernaez, Yan Liu, Jennifer R Kramer, Abbas Rana, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: It is unclear whether the model for end-stage liver disease-sodium (MELD-Na) score captures the clinical severity of acute-on-chronic liver failure (ACLF). We compared observed 90-day mortality in patients with ACLF with expected mortality based on the calculated MELD-Na and examined the consequences of underestimating clinical severity.

METHODS: We identified patients with ACLF during hospitalization for cirrhosis in 127 VA hospitals between 01/01/2004 and 12/31/2014. We examined MELD-Na scores by ACLF presence and grade. We used actual and observed 90-day mortality to estimate a standardized mortality ratio (SMR) by ACLF presence and grade. We used transplant center-specific median …

Clinical Efficacy Of Direct-Acting Antiviral Therapy For Recurrent Hepatitis C Virus Infection After Liver Transplantation In Patients With Hepatocellular Carcinoma, Mohamed Saleh Ismail, Manal Hassan, Saira Aijaz Khaderi, Wael Ahmed Yousry, Maha Mohsen Kamal El-Din, Mohamed Mohamed Bahaa El-Din, Osama Aboelfotoh El Sayed, Ahmed Omar Kaseb, John Alan Goss, Fasiha Kanwal, Prasun Kumar Jalal

Faculty, Staff and Students Publications

BACKGROUND: Recurrent hepatitis C virus (HCV) infection of transplanted liver allografts is universal in patients with detectable HCV viremia at the time of transplantation. Direct-acting antiviral (DAA) therapy has been adopted as the standard of care for recurrent HCV infection in the post-transplant setting. However, there are insufficient data regarding its efficacy in liver transplant (LT) recipients with a history of hepatocellular carcinoma (HCC), and the risk of HCC recurrence after DAA therapy is unknown.

AIM: To demonstrate predictors of DAA treatment failure and HCC recurrence in LT recipients.

METHODS: A total of 106 LT recipients given DAAs for recurrent …

Structural Characterization Of A Clinically Described Heparin-Like Substance In Plasma Causing Bleeding, Yanlei Yu, Karen Bruzdoski, Vadim Kostousov, Lisa Hensch, Shiu-Ki Hui, Fakiha Siddiqui, Amber Farooqui, Ahmed Kouta, Fuming Zhang, Jawed Fareed, Jun Teruya, Robert J Linhardt

Faculty, Staff and Students Publications

Heparin-like substances (HLS) have been described in various clinical situations, including in settings of liver disease associated with infection, transplant, and metastasis. HLS are generally attributed to circulating glycosaminoglycans. Initial results for this patient showed coagulopathy due to liver disease without HLS. Two weeks after liver transplantation, a 10 year-old female with liver failure patient began to bleed from catheter insertion sites, mouth, and nares and HLS was suspected. The patient subsequently died and these clinical samples resulted in the isolation of a single heparan sulfate (HS) present at high concentrations in the plasma. Analysis of this HS showed it …

Early Transplantation In Acute On Chronic Liver Failure: Who And When, Nadim Mahmud, Ruben Hernaez, Tiffany Wu, Vinay Sundaram

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Acute on chronic liver failure (ACLF) is a unique syndrome that afflicts patients with chronic liver disease and results in high short-term mortality, > 50% at 28 days in patients with severe ACLF (grade 3, ACLF-3). Given this prognosis, there is an urgent need to understand risk factors for this condition, as well as selection criteria for patients who may benefit from liver transplantation (LT).

RECENT FINDINGS: Several studies have identified risk factors for developing ACLF, including higher model for end-stage liver disease score, anemia, and morbid obesity, as well ACLF mortality, such as infection, increasing organ failures, …

Urinary Bile Acid Indices As Diagnostic And Prognosic Biomarkers For Liver Diseases, Jawaher Alamoudi

Theses & Dissertations

Hepatobiliary diseases result in the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues which may contribute to an unfavorable prognosis. We compared the urinary BA profile between 300 patients with hepatobiliary diseases vs. 103 healthy controls. Also, we investigated the use of the urinary BA profile to develop survival models to predict the prognosis of hepatobiliary diseases. The urinary BA profile, a set of non-BA parameters, and the adverse events of liver transplant and/or death were monitored in patients with cholestatic liver diseases for up to 7 years. The BA profile was characterized by calculating …

Post-Registration Experience Of Nivolumab In Advanced Hepatocellular Carcinoma: An International Study, Petros Fessas, Ahmed Kaseb, Yinghong Wang, Anwaar Saeed, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Uqba Khan, Chiehju Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Francesca Benevento, Hannah Hildebrand, Tiziana Pressiani, Yehia I Abugabal, Nicola Personeni, Yi-Hsiang Huang, Lorenza Rimassa, Celina Ang, Thomas Marron, David J Pinato

Faculty, Staff and Students Publications

BACKGROUND: Nivolumab is Food and Drug Administration approved in sorafenib-experienced, advanced hepatocellular carcinoma (HCC). Post-registration data of treatment in a real-world setting is lacking.

PATIENTS AND METHODS: We performed an international, multicenter observational study to confirm safety and efficacy of nivolumab in 233 patients treated outside clinical trials from eight centers in North America, Europe and Asia.

RESULTS: Patients received nivolumab for Barcelona Clinic Liver Cancer stage C (n=191, 92.0%) and Child-Pugh (CP) A (n=158, 67.8%) or B (n=75, 32.2%) HCC as first (n=85, 36.5%) or second to fourth systemic therapy line …