Hepatology Commons^™

Exosome Shedding Is Concordant With Objective Treatment Response Rate And Stratifies Time To Progression In Treatment Naïve, Non-Resectable Hepatocellular Carcinoma, Kelley G. Núñez, Dorota Wyczechowska, Mina Hibino, Tyler Sandow, Juan Gimenez, Ali R. Koksal, Yucel Aydin, Srikanta Dash, Ari J. Cohen, Paul T. Thevenot

School of Medicine Faculty Publications

Translational strategies to characterize and monitor extracellular vesicles such as exosome (EX) shedding and the clinical impact of this data within hepatocellular carcinoma (HCC) remains unclear. In this study, EX shedding was assessed in early-stage HCC and evaluated as a stratification factor for time to progression (TTP) following first-cycle liver-directed therapy (LDT). Plasma EXs were isolated from HCC patients undergoing LDT using ultracentrifugation. Purified EXs were stained using markers CD9 and CD63 and quantified using an ImageStreamX flow cytometer. Circulating EXs expressing CD9 were isolated at 10-fold higher levels compared to CD63. The intensity of CD9+ EX shedding following LDT …

Persistently Elevated Hbv Viral-Host Junction Dna In Urine As A Biomarker For Hepatocellular Carcinoma Minimum Residual Disease And Recurrence: A Pilot Study, Selena Y Lin, Dina Halegoua-De Marzio, Peter Block, Yu-Lan Kao, Jesse M. Civan, Fwu-Shan Shieh, Wei Song, Hie-Won Hann, Ying-Hsiu Su

Department of Medicine Faculty Papers

Hepatitis B virus (HBV)-host junction sequences (HBV-JSs) has been detected in the urine of patients with HBV infection. This study evaluated HBV-JSs as a marker of minimum residual disease (MRD) and tumor recurrence after treatment in HBV-hepatocellular carcinoma (HCC) patients. Archived serial urine DNA from two HBV–HCC with recurrence as confirmed by MRI and four HBV-related cirrhosis (LC) patients were used. Urinary HBV-JSs were identified by an HBV-targeted NGS assay. Quantitative junction-specific PCR assays were developed to investigate dynamic changes of the most abundant urinary HBV-JS. Abundant urinary HBV-JSs were identified in two cases of tumor recurrence. In case 1, …

Chronicles Of Hbv And The Road To Hbv Cure, Rukaiya Bashir Hamidu, Richard R. Hann, Hie-Won Hann

Division of Gastroenterology and Hepatology Faculty Papers

Chronic hepatitis B remains a major public health concern and a leading cause of morbidity and mortality worldwide, specifically through its causative role in chronic liver disease and hepatocellular carcinoma. Worldwide, it affects up to 292 million people. In this paper, we review the historic discovery of the hepatitis B virus and chronicle the significant advances in our understanding of the virus and its interactions with the human host to cause disease. We also overview advancements in therapies for hepatitis B virus and the current absence of curative therapies and highlight on-going therapeutic efforts in search of curative therapies to …

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 …

Cardiac Metastasis After Curative Treatment Of Hepatocellular Carcinoma: Risk Factors, Treatment Options, And Prognosis, Gaurav Jain, Mathew Otto, Mubeen Khan Mohammed Abdul, Manpreet Chadha, Ajay Sahajpal

Journal of Patient-Centered Research and Reviews

Hepatocellular carcinoma (HCC) is primary hepatic malignancy with a high incidence of recurrence. The risk of recurrence directly correlates to patient’s overall prognosis. Management of advanced HCC involves a combination of surgical resection, locoregional therapy, and systemic treatment. Distant metastases are rare, and intraventricular cardiac metastases are even more infrequent. This brief review details an illustrative case of cardiac metastasis after curative treatment of primary HCC and then summarizes the literature on risk factors, treatment options, and patient prognosis in the setting of distant metastases from HCC. Prognosis of metastasis to the heart is generally poor, and available evidence emphasizes …

Chronic Alcohol Exposure Induces Hepatocyte Damage By Inducing Oxidative Stress, Satb2 And Stem Cell-Like Characteristics, And Activating Lipogenesis, Wei Yu, Yiming Ma, Sushant K. Shrivastava, Rakesh K. Srivastava, Sharmila Shankar

School of Medicine Faculty Publications

Alcohol is a risk factor for hepatocellular carcinoma (HCC). However, the molecular mechanism by which chronic alcohol consumption contributes to HCC is not well understood. The purpose of the study was to demonstrate the effects of chronic ethanol exposure on the damage of human normal hepatocytes. Our data showed that chronic exposure of hepatocytes with ethanol induced changes similar to transformed hepatocytes that is, exhibited colonies and anchorage-independent growth. These damaged hepatocytes contained high levels of reactive oxygen species (ROS) and showed induction of the SATB2 gene. Furthermore, damaged hepatocytes gained the phenotypes of CSCs which expressed stem cell markers …

Protective Benefit Of Minimally Invasive Liver Surgery For Hepatocellular Carcinoma Prior To Transplant, Simone Khouzam, Duilio Pagano, Marco Barbara, Vito Di Marco, Giada Pietrosi, Marco Maringhini, Marco Canzonieri, Sergio Calamia, Salvatore Gruttadauria

Department of Medicine Faculty Papers

Aim: The purpose of this study is to assess the benefit of laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) given recurrence and future need for liver transplantation (LT). Methods: Data on liver resections were gathered from the Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione (IRCCS-ISMETT) from 2003-2021. A retrospective analysis of 1408 consecutive adult patients who had a liver resection was performed with categorization based on the underlying disease process. A sub-analysis studied the 291 patients who had an LLR with an intention to transplant approach after LLR. Results: …

In Patients With Hepatocellular Carcinoma (Hcc) (P), Is Bevacizumab With Atezolizumab (I) More Effective Than Sorafenib (C) In Long-Term Clinical Prognosis (O)?, Joon Lee

Capstone Showcase

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death globally. China contributes to half of the global incidence of liver cancer, with about 70-85% being HCC. Definitive treatment for this condition would be surgical resection with liver transplant but for obvious reasons, the majority of affected patients are unable to meet the necessary criteria. Sorafenib is a form of chemotherapy that has been the mainstay treatment of HCC since its approval in 2007. More recently, the combination of Bevacizumab and Atezolizumab has shown greater efficacy in the treatment of unresectable HCC. Additionally, this new combination therapy shows favorable …

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 Publications

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 …

Updates On The Diagnosis And Management Of Hepatocellular Carcinoma, Aimun Raees, Muhammad Kamran, Hasan Özkan, Wasim Jafri

Section of Gastroenterology

Introduction: Globally, the incidence, as well as mortality, related to hepatocellular carcinoma (HCC) is on the rise, owing to relatively few curative options. Underlying cirrhosis is the most common etiology leading to HCC, but risk factors of cirrhosis show great regional variability. Over the years, there has been a steady development in the diagnostic and therapeutic modalities of HCC, including the availability of a wide range of systemic chemotherapeutic agents. We aim to review the recent advancements in the diagnostic and therapeutic strategies for HCC.
Methodology: The literature search was done using databases PubMed, Cochrane, and Science Direct, and the …

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 …

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 …

Surveillance, Prevention And Surgical Treatments For Hepatocellular Carcinoma, Kerui Xu

Theses & Dissertations

Liver cancer is the second-leading cause of cancer death, representing roughly 9.1% of all cancer mortality. Of all primary cancers of the liver, hepatocellular carcinoma (HCC) accounts for roughly 85%. HCC has been increasing in the U.S. and other countries. In particular, HCC places a huge burden on the Chinese population, as China alone consists of approximately 50% of the total HCC cases and deaths. In China, chronic hepatitis B virus (HBV) infection is the leading cause for developing HCC. The two challenges in prevention and control of HCC experienced in China are low rates of HCC screening among the …

A Comparison Of Screening, Prevention, And Management For Hepatitis B Patients Between The Us And Chinese Healthcare Systems, Thomas Chen, James D. Plumb, Md

Phase 1

Introduction: Hepatitis B (HBV) is a complex disease entity with potentially serious outcomes, including developing hepatocellular carcinoma (HCC). HBV is estimated to be responsible for about 50-80% of HCC cases worldwide, and 75-95% of HCC cases in HBV endemic regions.¹ HBV and HCC are great concerns especially in East Asian countries like China. In China, HCC ranks as the 2^nd most common cancer and 2^nd in cancer mortality, both behind only lung cancer.¹ China is considered an endemic HBV region, with about 100-150 million people infected. In comparison, only an estimated 550,000-2 million people are chronically …

Cell-Free Circulating Mitochondrial Dna Content And Risk Of Hepatocellular Carcinoma In Patients With Chronic Hbv Infection., Ling Li, Hie-Won Hann, Shaogui Wan, Richard Hann, Chun Wang, Yinzhi Lai, Xishan Ye, Alison Evans, Ronald E. Myers, Phd, Dsw, Zhong Ye, Bingshan Li, Jinliang Xing, Hushan Yang

Department of Medicine Faculty Papers

Recent studies have demonstrated a potential link between circulating cell-free mitochondrial DNA (mtDNA) content and cancers. However, there is no study evaluating the association between circulating mtDNA as a non-invasive marker of hepatocellular carcinoma (HCC) risk. We conducted a nested case-control study to determine circulating mtDNA content in serum samples from 116 HBV-related HCC cases and 232 frequency-matched cancer-free HBV controls, and evaluate the retrospective association between mtDNA content and HCC risk using logistic regression and their temporal relationship using a mixed effects model. HCC cases had significantly lower circulating mtDNA content than controls (1.06 versus 2.47, P = 1.7 …

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 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 …

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

Dissertations & 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 …