Hepatology Commons^™

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 …

The Evolution Of Device-Assisted Enteroscopy: From Sonde Enteroscopy To Motorized Spiral Enteroscopy, Freddy Nehme, Hermant Goyal, Abhilash Perisetti Md, Ben Tharian, Neil Sharma Md, Tony C. Tham, Rajiv Chhabra

PCI Publications and Projects

THIS ARTICLE IS PART OF THE RESEARCH TOPIC: Recent Updates in Advanced Gastrointestinal Endoscopy

The introduction of capsule endoscopy in 2001 opened the last “black box” of the gastrointestinal tract enabling complete visualization of the small bowel. Since then, numerous new developments in the field of deep enteroscopy have emerged expanding the diagnostic and therapeutic armamentarium against small bowel diseases. The ability to achieve total enteroscopy and visualize the entire small bowel remains the holy grail in enteroscopy. Our journey in the small bowel started historically with sonde type enteroscopy and ropeway enteroscopy. Currently, double-balloon enteroscopy, single-balloon enteroscopy, and spiral …

Radioembolization With Chemotherapy For Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase Iii Trial, Mary F Mulcahy, Armeen Mahvash, Marc Pracht, Amir H Montazeri, Steve Bandula, Robert C G Martin, Ken Herrmann, Ewan Brown, Darryl Zuckerman, Gregory Wilson, Tae-You Kim, Andrew Weaver, Paul Ross, William P Harris, Janet Graham, Jamie Mills, Alfonso Yubero Esteban, Matthew S Johnson, Constantinos T Sofocleous, Siddharth A Padia, Robert J Lewandowski, Etienne Garin, Philip Sinclair, Riad Salem

Faculty, Staff and Student Publications

PURPOSE: To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM).

METHODS: In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and

RESULTS: Four hundred twenty-eight patients from …

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. …

Does Low Income Effects 5-Year Mortality Of Hepatocellular Carcinoma Patients?, Dong Jun Kim, Ji Won Yoo, Jong Wha Chang, Takashi Yamashita, Eun-Cheol Park, Kyu-Tae Han, Seung Ju Kim, Sun Jung Kim

School of Medicine Faculty Research

Background: In Korea, the universal health system offers coverage to all members of society. Despite this, it is unclear whether risk of death from hepatocellular carcinoma (HCC) varies depending on income. We evaluated the impact of low income on HCC mortality. Methods: The Korean National Health Insurance sampling cohort was used to identify new HCC cases (n = 7325) diagnosed between 2004 and 2008, and the Korean Community Health Survey data were used to investigate community-level effects. The main outcome was 5-year all-cause mortality risk, and Cox proportional hazard models were applied to investigate the individual- and community-level factors associated …

Increased Diagnosis Of Hepatocellular Carcinoma In Hospitalized Patients With Alcohol Related Hepatitis After The Covid-19 Outbreak: A Global Multi-Center Propensity Matched Analysis., Abhilash Perisetti Md, Randeep Kaur, Ragesh Thandassery

PCI Publications and Projects

No abstract provided.

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 …

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 …

Modulation Of Immune Checkpoints By Chemotherapy In Human Colorectal Liver Metastases., Neda Jabbari, Heidi L Kenerson, Christopher Lausted, Xiaowei Yan, Changting Meng, Kevin M Sullivan, Priyanka Baloni, Dani E Bergey, Venu G Pillarisetty, Leroy Hood, Raymond S Yeung, Qiang Tian

Articles, Abstracts, and Reports

Metastatic colorectal cancer (CRC) is a major cause of cancer-related death, and incidence is rising in younger populations (younger than 50 years). Current chemotherapies can achieve response rates above 50%, but immunotherapies have limited value for patients with microsatellite-stable (MSS) cancers. The present study investigates the impact of chemotherapy on the tumor immune microenvironment. We treat human liver metastases slices with 5-fluorouracil (5-FU) plus either irinotecan or oxaliplatin, then perform single-cell transcriptome analyses. Results from eight cases reveal two cellular subtypes with divergent responses to chemotherapy. Susceptible tumors are characterized by a stemness signature, an activated interferon pathway, and suppression …

Long Non-Coding Rna (Lncrna) As A New Biomarker For Hepatocellular Carcinoma (Hcc) Progression And Drug Resistance, Areeb Masood, Sanjaya Satapathy, Manish Tripathi

MEDI 9331 Scholarly Activities Clinical Years

Hepatocellular carcinoma (HCC) is a primary malignant liver tumor that commonly occurs as a progression of chronic liver inflammation due to long-standing viral hepatitis infection, toxins, metabolic conditions, and congenital disorders. In 2018, HCC was the 4th leading cause of cancer-related deaths worldwide, accounting for approximately 780,000 deaths in total.

HCC’s prognosis is directly correlated with early detection. Unfortunately, HCC has an asymptomatic pattern of growth in the early stages of the disease which makes early detection challenging. When HCC progresses to advanced stages, it leaves clinicians with limited therapeutic and curative options, leading to high rates of morbidity and …

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 …

Management And Treatment Of Hepatocellular Carcinoma With Immunotherapy: A Review Of Current And Future Options, Shima Ghavimi, Tehila Apfel, Hamed Azimi, Alana Persaud

Internal Medicine

With mortality rates of liver cancer doubling in the last 20 years, this disease is on the rise and has become the fifth most common cancer in men and the seventh most common cancer in women. Hepatocellular carcinoma (HCC) represents approximately 90% of all primary liver cancers and is a major global health concern. Patients with HCC can be managed curatively with surgical resection or with liver transplantation, if they are diagnosed at an early stage. Unfortunately, most patients with HCC present with advanced stages of the disease and have underlying liver dysfunction, which allows only 15% of patients to …

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 …

A Descriptive Study Of Racial Inequalities In Mortality From Hepatocellular Cancer Before And After Licensure Of Lifesaving Drugs For Hepatitis C Virus In The United States, Robert S Levine, Maria C Mejia, Jason L Salemi, Sandra J Gonzalez, Muktar H Aliyu, Baqar A Husaini, Roger J Zoorob, Charles H Hennekens

Faculty, Staff and Students Publications

BACKGROUND: Since 1979, mortality from hepatocellular cancer (HCC) has doubled in the United States (US). Lifesaving drugs, prohibitively expensive for some, were approved and marketed to treat hepatitis C virus (HCV), a major risk factor for HCC, beginning in 1997. After the prior introduction of other lifesaving innovations, including active retroviral drug therapy for human immunodeficiency virus and surfactant for respiratory distress syndrome of the newborn, racial inequalities in their mortalities increased in the US. In this descriptive study, we explored racial inequalities in mortality from HCC before and after licensure of HCV drugs in the US.

METHODS: The US …

Tumor Slice Culture As A Biologic Surrogate Of Human Cancer., Heidi L Kenerson, Kevin M Sullivan, Yongwoo D Seo, Kathryn M Stadeli, Cigdem Ussakli, Xiaowei Yan, Christopher G Lausted, Venu G Pillarisetty, James O Park, Kimberly J Riehle, Matthew Yeh, Qiang Tian, Raymond S Yeung

Articles, Abstracts, and Reports

Background: The tumor microenvironment (TME) is critical to every aspect of cancer biology. Organotypic tumor slice cultures (TSCs) preserve the original TME and have demonstrated utility in predicting drug sensitivity, but the association between clinicopathologic parameters and

Methods: One hundred and eight fresh tumor specimens from liver resections at a tertiary academic center were procured and precisely cut with a Vibratome to create 250 μm × 6 mm slices. These fixed-dimension TSCs were grown on polytetrafluoroethylene inserts, and their metabolic activities were determined by a colorimetric assay. Correlation between baseline activities and clinicopathologic parameters was assessed. Tissue CEA mRNA expression …

Reduced Length Of Stay In Major Hepatectomy Surgery After Implementation Of An Enhanced Recovery Pathway In The United States Veteran Population, Yvonne Nguyen Md, Marilyn Mcnulty Np, Leopoldo Fernandez Md, Michael R. Kazior Md

Graduate Medical Education (GME) Resident and Fellow Research Day Posters

Introduction

Enhanced recovery after surgery (ERAS) pathways are associated with better postoperative recovery, however, evidence is lacking in major liver surgery, .This study aimed to evaluate the impact of an ERAS pathway in U.S. veterans undergoing major hepatectomy surgery. We hypothesized that the adoption of an ERAS pathway reduces decreased length of stay (LOS).

Methods

After approval from the Hunter Holmes McGuire VA Medical Center IRB, we compared data from consecutive patients undergoing elective open hepatectomy within an ERAS pathway (January 2019-December 2019) to a previous cohort of patients before introduction of ERAS (July 2016-December 2017). One surgeon performed all …

Liver Cancer: A Leading Cause Of Cancer Death In The United States And The Role Of The 1945–1965 Birth Cohort By Ethnicity, Paulo S. Pinheiro, Karen E. Callahan, Patricia D. Jones, Cyllene Morris, Justine M. Ransdell, Deukwoo Kwon, Clyde Perry Brown, Erin N. Kobetz

Environmental & Global Health Faculty Research

No abstract provided.

Rare Sarcomatoid Carcinoma Of The Liver In A Patient With No History Of Hepatocellular Carcinoma: A Case Report, Kevat B. Patel, Rita H. Hawarny, Elizabeth Saunders, Marc Hettlinger, Niru Nahar

Marshall Journal of Medicine

Sarcomatoid carcinoma is a rare malignant tumor of unknown pathogenesis characterized by poorly differentiated carcinoma tissue containing sarcoma-like differentiation of either spindle or giant cell and rarely occurs in the gastrointestinal tract and hepatobiliary-pancreatic system.¹ Primary hepatic sarcomatoid carcinoma accounts for only 0.2 % of primary malignant liver tumors, and 1.8% of all surgically resected hepatocellular carcinomas.² The majority of hepatic sarcomatoid carcinoma cases appear to occur simultaneously with hepatocellular or cholangiocellular carcinoma.³ The preferred treatment for hepatic sarcomatoid carcinoma is surgical resection and the overall prognosis is poor.⁴ This case depicts a 62-year-old female whom …

Prothrombin Complex Concentrates Or Recombinant Factor Viia Are More Effective Than Fresh-Frozen Plasma At Lowering Inr In Patients With Liver Disease, Abel J. Ignatius

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Kwon JO, MacLaren R. Comparison of fresh-frozen plasma, four-factor prothrombin complex concentrates, and recombinant factor VIIa to facilitate procedures in critically ill patients with coagulopathy from liver disease: a retrospective cohort study. Pharmacotherapy. 2016;36(10):1047-1054. doi: 10.1002/phar.1827

Metastatic Breast Cancer Presenting As Painless Jaundice, Daniel S. Wilen, Donald J. Mcmahon, Brian J. Blair, Joanne Kaiser-Smith, Darshan B. Roy

Rowan-Virtua Research Day

Breast cancer is the most commonly diagnosed cancer in women in the United States. Treatment options are wide-­‐ ranging based on a multitude of factors, including extent of disease and receptor positivity. Following treatment, a relapse-­‐free interval ≥ 2 years carries a more favorable prognosis.

We present a case involving a female with history of breast cancer and relapse-­free interval of 15 years who unfortunately presented with metastatic disease involving the liver, bone, and lymph nodes.

Inhibition Of Insulin‐Like Growth Factor 1 Receptor Enhances The Efficacy Of Sorafenib In Inhibiting Hepatocellular Carcinoma Cell Growth And Survival, Fang Wang, Thomas Bank, George Malnassy, Maribel Arteaga, Na Shang, Annika Dalheim, Xianzhong Ding, Scott J. Cotler, Mitchell F. Denning, Michael I. Nishimura, Peter Breslin, Wei Qiu

Biology: Faculty Publications and Other Works

Hepatocellular carcinoma (HCC) is the fifth most common primary cancer and second largest cause of cancer‐related death worldwide. The first‐line oral chemotherapeutic agent sorafenib only increases survival in patients with advanced HCC by less than 3 months. Most patients with advanced HCC have shown limited response rates and survival benefits with sorafenib. Although sorafenib is an inhibitor of multiple kinases, including serine/threonine‐protein kinase c‐Raf, serine/threonine‐protein kinase B‐Raf, vascular endothelial growth factor receptor (VEGFR)‐1, VEGFR‐2, VEGFR‐3, and platelet‐derived growth factor receptor β, HCC cells are able to escape from sorafenib treatment using other pathways that the drug insufficiently inhibits. The aim …

Glypican-3 And Cd81 Promote Development Of Hepatocellular Carcinoma And Hepatoblastoma Through Negative Selection., Yuhua Xue, Wendy Mars, William Bowen, Aatur D. Singhi, Sarangarajan Ranganathan, George K. Michalopoulos

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Intrahepatic Cholangiocarcinoma Presenting As Li-Rads 5 "Hcc", Raja K. Dhanekula, Md, Donald Mitchell, Md, John Farber, Md, Ashwin R. Sama, Md, Jesse M. Civan, Md

Division of Gastroenterology and Hepatology Posters

Background

• Hepatocellular Carcinoma (HCC), if within Milan Criteria, is an indication for liver transplantation.

• In contrast, intrahepatic cholangiocarcinoma (IHCC) is a contra-indication to liver transplantation due to high rates of recurrence.

• LI-RADS 5 classification (synonymous with OPTN-5) carries a near 100% positive predictive value for HCC, allowing prioritization of patients for liver transplantation without histological confirmation.

• The “LI-RADS M” classification indicates the presence of malignancy not meeting diagnostic criteria for HCC. In theory, IHCC lesions should be identified as LI-RADS M and not LI-RADS 5.

Vitamin D Deficiency Promotes Liver Tumor Growth In Transforming Growth Factor-Β/Smad3-Deficient Mice Through Wnt And Toll-Like Receptor 7 Pathway Modulation., Jian Chen, Lior H Katz, Nina M Muñoz, Shoujun Gu, Ji-Hyun Shin, Lopa Mishra, +13 Additional Authors

Surgery Faculty Publications

Disruption of the TGF-β pathway is associated with liver fibrosis and suppression of liver tumorigenesis, conditions associated with low Vitamin D (VD) levels. However, potential contributions of VD to liver tumor progression in the context of TGF-β signaling remain unexplored. Our analyses of VD deprivation (VDD) in in vivo models of liver tumor formation revealed striking three-fold increases in tumor burden in Smad3(+/-) mice, with a three-fold increase in TLR7 expression compared to controls. ChIP and transcriptional assays confirm Smad3 binding at two TLR7 promoter SBE sites. Molecular interactions between TGF-β pathway and VDD were validated clinically, where an absence …

Activation Of Signal Transduction Pathways During Hepatic Oncogenesis, W Chung, M Kim, S De La Monte, L Longato, R Carlson, B L. Slagle, X Dong, J R. Wands

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Understanding the molecular pathogenesis of hepatocellular carcinoma (HCC) is essential to identify therapeutic targets. A hepatitis B virus (HBV) related double transgenic murine model was developed. METHODS: Liver specific expression of HBV X protein (HBx) and insulin receptor substrate 1 (IRS1) was achieved and transgenic mice were followed from birth to age 21 months. Liver and tumor tissue were assessed for histologic changes as well as activation of signal transduction pathways by qRT-PCR and multiplex ELISA protein assays. RESULTS: Overexpression of HBx and IRS1 stimulates liver cell proliferation in the double transgenic mice. Only the male mice …

Analysis Of The Role Of Astrocyte Elevated Gene-1 In Normal Liver Physiology And In The Onset And Progression Of Hepatocellular Carcinoma, Chadia L. Robertson

Theses and Dissertations

First identified over a decade ago, Astrocyte Elevated Gene-1 (AEG-1) has been studied extensively due to early reports of its overexpression in various cancer cell lines. Research groups all over the globe including our own have since identified AEG-1 overexpression in cancers of diverse lineages including cancers of the liver, colon, skin, prostate, breast, lung, esophagus, neurons and neuronal glia as compared to matched normal tissue. A comprehensive and convincing body of data currently points to AEG-1 as an essential component, critical to the progression and perhaps onset of cancer. AEG-1 is a potent activator of multiple pro-tumorigenic signal transduction …

Burkitt Lymphoma Presenting As Left Lateral Rectus Palsy, Daniel Tseytlin Do, Usman Shah Md

Department of Medicine

No abstract provided.