Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Infections

Digestive System Diseases

Heart and Blood Diseases

Rare Diseases

Lymphoma

Hepatitis A

Hepatitis C

Hepatitis

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Virus Diseases

Lymphoma, B-Cell

Waldenstrom Macroglobulinemia

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

B-cell Lymphoma

Lymphosarcoma

Follicular Lymphoma

Marginal Zone Lymphoma

Indolent B Cell Lymphoma

All Drugs and Chemicals

Anti-Infective Agents

Hepatitis C Antibodies

Sofosbuvir

Antiviral Agents

Ledipasvir

Ledipasvir, sofosbuvir drug combination

Harvoni® (90 mg ledipasvir and 400 mg sofosbuvir) one tablet daily for 12 weeks

To assess whether Harvoni® (ledipasvir and sofosbuvir) could eradicate HCV and lead to durable complete remission of these lymphomas.

Ledipasvir and sofosbuvir

Sung-Hsin Kuo, M.D.,Ph.D.

We and other investigators have revealed an association between Hepatitis C virus (HCV) seropositivity and an increased risk of developing marginal zone B-cell lymphoma (MZ), lymphoplasmacytic lymphoma (LPL, also known as Waldenström's macroglobulinemia), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). The sustained virologic response (SVR) to treatment with interferon or pegylated (Peg)IFN with ribavirin was closely associated with the regression of HCV-associated B-cell NHL (mainly MZL, and LPL).

Currently, the second-generation direct-acting antiviral agents (DAAs), such as sofosbuvir, have been shown to have a higher cure rate, less side effects, and a shorter duration of therapy for chronic HCV infection. After the approval of DAA for HCV therapy, several recent anecdotal case reports showed that indolent low-grade B-cell NHLs regressed after HCV clearance by DAAs. It is noted that the time to complete remission of these lymphomas was around 20 to 24 weeks after starting DAAs. These findings indicate that DAAs can eradicate the trigger of lymphomagenesis by curing chronic HCV infection.

Because DAAs are more potent and efficient than pegylated (Peg) interferon plus ribavirin and well-tolerated for the treatment of HCV infection, it is reasonable to use DAAs as the frontline treatment for HCV-positive patients with indolent B-cell NHL, such as MZL, LPL, and low-grade FL, who do not require immediate cytoreductive therapy. The aim of this proposal is to assess whether Harvoni® (ledipasvir and sofosbuvir) could eradicate HCV and lead to durable complete remission of these lymphomas..

Although several epidemiological studies, including our study have been demonstrated the link between HCV and B-cell non-Hodgkin's lymphoma (NHL), the direct evidence of the HCV-associated-NHL remains uncertain. Direct antiviral agents (DAA) have been shown to have a higher cure rate, less side effects, and a shorter duration of therapy for chronic HCV infection. Whether DAA treatment can cure HCV-associated indolent B-cell NHL remains unclear? If yes, a direct evidence of HCV-associated lymphomagenesis will be approved. Because DAAs are more potent and efficient than pegylated (Peg) interferon plus ribavirin and well-tolerated for the treatment of HCV infection, it is reasonable to use DAAs as the frontline treatment for HCV-positive patients with indolent B-cell NHL, such as MZL, LPL, and low-grade FL, who do not require immediate cytoreductive therapy. The aim of this proposal is to assess whether Harvoni® (ledipasvir and sofosbuvir) could eradicate HCV and lead to durable complete remission of HCV-associated indolent B-cell NHL.

In the translational part, we will assess the expression pattern of BAFF-related canonical and non-canonical NF-κB signaling molecules by immunohistochemical (IHC) staining, and t(11;18)(q21;q21), and t(14;18)(q32;q21) by fluorescence in situ hybridization (FISH) in pre-treatment tumors samples of patients in prospectively predicting the antiviral responsiveness of HCV-positive indolent B-cell NHLs. The serum cytokines and chemokines, IFN-gamma, TNF-alpha, IL-4, IL-5, IL-6, IL-13 and CXCL13, BAFF level, and HCV RNA load before and after DAA treatment in HCV-associated indolent B-cell NHLs will be examined. The genotype of the HLA class II, and cloning followed by sequences of the VH region of the immunoglobulin gene derived from pre-treatment tumor samples will be assessed.

New Direct-Acting Antiviral Agent, HARVONI® (ledipasvir/sofosbuvir)

Antiviral Agent HARVONI® for the Treatment of HCV-associated Indolent B-Cell Lymphoma

A Pilot Phase II Study of New Direct-Acting Antiviral Agent, HARVONI® (Ledipasvir/Sofosbuvir), for the Treatment of Genotype 1 or 2 HCV-Associated Indolent B-Cell Non- Hodgkin's Lymphoma

The complete remission rate by using Harvoni® (ledipasvir and sofosbuvir) as the first-line line therapy.

Complete remission and partial remission rate

The assessment of toxicity during the first 3 months

National Taiwan University Hospital

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Nervous System Diseases

Behaviors and Mental Disorders

Syndrome

Carcinoma

Carcinoma, Hepatocellular

Apnea

Sleep Apnea Syndromes

Sleep Apnea, Obstructive

Fatty Liver

Liver Diseases

Non-alcoholic Fatty Liver Disease

Neoplasms, Glandular and Epithelial

Gastrointestinal Diseases

Respiration Disorders

Respiratory Tract Diseases

Signs and Symptoms, Respiratory

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Parasomnias

Sleep Disorders, Intrinsic

Dyssomnias

Sleep Wake Disorders

Visceral Steatosis

The study is focused on patients suffering from NASH-induced HCC. Each patient with NASH-related HCC will be paired with 2 patients with non NASH-related HCC (HCV-induced CHC).

HCV-related HCC has been chosen as control population for several reasons: HCV represent a common etiology of HCC; with a distinct pathophysiology distinct from that of post-NASH HCC; populations with post-NASH and post-HCV CHC share similar epidemiological characteristics.

Diagnosis of OSA will be based on the 3% Oxygen Desaturation Index (IDO) obtained by home nocturnal oximetry. The oximetry recordings will be centralized in sleep laboratory of the University Hospital of Grenoble Alpes. Oximetry data will be analyzed by a technician from the sleep laboratory of the University Hospital of Grenoble Alpes

Nocturnal oximetry

Jean-Louis Pépin, MD,PHD

Thomas Decaens, MD,PHD

Obstructive sleep apnea (OSA), one of the most frequent respiratory diseases, could represent a major worsening factor in a non alcoholic steatohepatitis and neoplastic context. Our hypothesis is that OSA promotes the prevalence of HCC related to NASH. This national, multicenter study aims to compare the prevalence of OSA in a group of patient curatively resected for NASH-related HCC with a group of HCV-related HCC.

Obstructive Sleep Apnea (OSA) is a common respiratory disease characterized by the occurrence of recurrent episodes of partial or total obstruction of the upper airway called hypopneas and apneas respectively. These episodes are associated with the repetitive occurrence of the desaturation-reoxygenation sequences, the so-called chronic intermittent hypoxia (IH) which is the major stimulus underlying main cardiovascular, metabolic consequences and pro-inflammatory state found in patients with OSA. Recent data from cohort studies have established that OSA is an even greater risk factor for cancer-related mortality. Hepatocellular carcinoma (HCC) is the second cancer related death worldwide and has an increasing impact in developed countries. The epidemic of metabolic syndrome (MS) plays a growing role in the occurrence of metabolic steatohepatitis (NASH) related HCC. Concerning transition from NASH to NASH-related HCC, neither the frequency nor the underlying mechanism are known. Very recently, a link between OSA (IH) and NASH has been highlighted. OSA and intermittent hypoxia should be a major worsening factor in a neoplastic context. Our hypothesis is that OSA promotes the prevalence of HCC in a context of NASH.

The objective is to compare the prevalence of OSA between patients with NASH-related and hepatitis C virus (HCV)-related HCC. In this type 3, cross-sectional, multicenter, national, non-randomized study patients suffering from a NASH-related or HCV-related hepatocellular carcinoma will be recruited. Investigators expect to show a higher prevalence of OSA in patients with HCC NASH-related but also a shorter overall survival. Complementary ex vivo studies on tumor samples will be conducted in order to explore the mechanisms by which OSA and IH would promote carcinogenesis

Sleep Apnoea Syndrome and Hepatocellular Carcinoma

Evaluation of the Prevalence of Sleep Apnea Syndrome in Patients With Hepatocellular Carcinoma

Number of patient presenting an obstructive apnea syndrome diagnosed by oxymetry

3% IDO represents the number of oxygen desaturation of at least 3% per hour of oxymetry recording, measured by one oximetry measurement during a single night at the patient's home.

2% IDO represents the number of oxygen desaturation of at least 2% per hour of oxymetry recording, measured by one oximetry measurement during a single night at the patient's home.

4% IDO represents the number of oxygen desaturation of at least 4% per hour of oxymetry recording, measured by one oximetry measurement during a single night at the patient's home.

Micro-arousals associated with desaturation will be measured to characterize sleep fragmentation

The time spent with a saturation less than 90 % (Tsat90 in second) to characterize oxygen desaturations and OSA severity

The Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality. Consisting of 19 items, the PSQI measures several different aspects of sleep. Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality.

The Epworth sleepiness scale (ESS) is a self-administered questionnaire that's routinely used by doctors to assess daytime sleepiness. The person filling in the questionnaire rates how likely they are to doze off during the day in 8 different situations.The test evaluate the tendency to become sleepy on a scale of 0, no chance of dozing, to 3, high chance of dozing.

Number of patient presenting an obstructive apnea syndrome diagnosed by oxymetry in both subpopulations: cirrhotic and non-cirrhotic.

NAFLD Activity Score includes the degree of steatosis, hepatocyte ballooning, lobular inflammation and fibrosis. Nas score is between 0 and 16.

The Brunt score for NASH patients is used to evaluate fibrosis stage. The score is between 1 and 4.

The METAVIR score is used to evaluate fibrosis stage for HCV patients. The score is between 0 and 4.

Tumor stage evaluated by BCLC classification scale :0,A,B,C and D values (0 for Stage 0 Very early stage, D for terminal stage)

Tumor size (expressed in cm) is asociated to HCC prognostic the size of the tumor is associated with the prognosis of the HCC

The tumor differentiation is classified in 3 levels: low, moderate or high level of tumor differentiation

Presence or absence of tumor vascular invasion

Number of tumoral satellite nodules (multifocality)

Plasma alpha fetoprotein (AFP) level expressed in ng/ml

Overall survival at 1 and 2 years will be collected.

Tumor-free survival at 1 and 2 years will be collected.

Non-recurrence-free survival at 1 and 2 years will be retrospectively or prospectively collected.

University Hospital, Grenoble

Gland and Hormone Related Diseases

Thyroid Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hematologic Neoplasms

Communicable Diseases

Thyroid Neoplasms

Thyroiditis

Hepatitis, Viral, Human

Enterovirus Infections

Picornaviridae Infections

RNA Virus Infections

Blood-Borne Infections

Flaviviridae Infections

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Endocrine System Diseases

This study will investigate the possible relationship between infection with hepatitis C virus (HCV) and the development of certain hematologic cancers (Non-Hodgkin's lymphoma, Hodgkin's lymphoma, chronic lymphocytic leukemia, multiple myeloma) and thyroid cancer. HCV causes chronic hepatitis, cirrhosis, and liver cancer. It is transmitted primarily through injection drug use and transfusion of infected blood. Studies have shown that HCV may also be linked to hematologic cancers and thyroid cancer.

This retrospective study will examine medical records from veterans with and without HCV infection who previously received treatment in the Veterans Administration medical system. Data collected on each subject will include the subject's race, sex, age and era of military service, presence of liver disease or thyroiditis at their baseline clinic visit, number of inpatient visits in the past 5 years and outpatient visits in the past year, and the presence of various specified cancers. The prevalence of cancer and other conditions among HCV-infected subjects and non-HCV infected subjects at baseline and the subsequent development of the cancers of interest in these two groups will be compared and analyzed for a possible causal relationship.

Hepatitis C virus (HCV) may be a cause of hematologic malignancies and thyroid cancer. HCV infection is common among U.S. military veterans receiving care in the Veterans Administration healthcare system. The investigators propose a retrospective cohort study using VA administrative databases. A cohort of approximately 147,000 HCV-infected veterans has been identified for the period 1997-2004. Likewise, a cohort of approximately 573,000 HCV-uninfected veterans has been identified for the same period. These subjects are being evaluated for the diagnosis of hematologic malignancies, thyroid cancer, and related medical conditions as recorded in VA databases. The comparison of the prevalence and incidence of these cancers in the two cohorts will provide a test of the hypothesis that HCV infection can cause these cancers.

The investigators will also evaluate the association between HCV infection and several other medical conditions, which might be related to HCV infection, specifically: immune thrombocytopenic purpura, autoimmune hemolytic anemia, cholangiocarcinoma, cholangitis, and pancreatic cancer.

Association Between Hepatitis C Virus Infection and Hematologic and Thyroid Cancers

Associations of Hematologic Malignancies and Thyroid Cancer With HCV Infection Among US Military Veterans

National Cancer Institute (NCI)

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Oral Squamous Cell Carcinoma

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Sections (4-5 microns thick) will be cut for the immunohistochemical procedure, from each paraffin block and placed on positively charged (Opti-plus) slides by the technicians in the Oral and Maxillofacial laboratory setting.

Hep C cAg : sc-58144, santa cruz biotechnology, USA) a mouse monoclonal antibody raised against Hepatitis C virus will be purchased and used for immunohistochemical staining.

Histological diagnosis of H\&E stained sections will be performed according to WHO guidelines by 2 independent pathologists.

oral squamous cell carcinoma

Nora Ali, Msc

Compare Hepatiis C Virus (HCV) detection between oral squamous cell carcinoma (OSCC) and normal tissues, to determine the possible relationship between HCV and OSCC.

Patient / Population: Paraffin embedded tissue samples of OSCC. Indicator: OSCC patients Control: Normal patients Formalin fixed paraffin embedded specimens from blocks retrieved from the archives of the Oral and Maxillofacial Pathology Department, Faculty of dentistry, Kasr Alini hospital setting from January 2014 till February 2018. All clinical and histopathological data from medical reports, will be reviewed and data will be collected regarding age, sex, tumor location, history of smoking and alcohol consumption, nodal status, tumor recurrences and histological classification of the patients. The specimens will be obtained from 2 groups:-

1. OSCC specimens. Histological diagnosis of H\&E stained sections will be performed according to World health organisation (WHO) guidelines by 2 independent pathologists.
2. Normal oral mucosa specimens (control).

outcome: I) Immunohistochemical detection of Hepatitis C core antigen (Hep C cAg) : sc-58144, santa cruz biotechnology, USA) a mouse monoclonal antibody raised against Hepatitis C virus will be purchased and used for immunohistochemical staining. Staining procedure using an automated system Ventana Benchmark. The four µm thick paraffin embedded tissue sections will be deparaffinized in three changes of xylene then microwaved for antigen retrieval. The slides will be incubated with primary antibody overnight in the humidity chamber at room temperature. Then, the slides will be incubated with secondary antibody. The peroxidase activity will be made visible with diaminobenzidine. Finally, counterstaining will be obtained using Mayer's hematoxylin.

The immunostained sections will be examined using analyzer computer system (Germany).

Hepatitis C Virus Detection in Oral Squamous Cell Carcinoma

Hepatitis C Virus Detection in Oral Squamous Cell Carcinoma. (Retrospective-cohort Study)

Hepatitis C core antigen by immunohistochemical analysis

Cairo University

assistant lecturer, Oral and Maxillofacial pathology

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

The data of breast cancer patients treated at OCMU in the last 10 years will be retrieved from the hospital data filing system. All consecutive patients with biopsy-proven invasive breast cancer will be included.

A group of age-matched women from the same geographical distribution who are healthy volunteers or hospital patients without cancer diagnosis will serve as a control group for the HCV prevalence. We aim at a sample size with a study-to-control ratio of 1:3.

Hepatitis C viral infection is a major health problem in Egypt. The management of breast cancer patients is often complicated by the presence of associated HCV infection. This study aims at investigating the epidemiological association of the two conditions. It will also investigate the possible correlation with treatment outcome.

Breast cancer is the most common cancer in adult Egyptian females. The world's highest prevalence of hepatitis C virus is found in Egypt. Several investigators examined the epidemiological association of HCV with breast cancer. Published literature reports conflicting results regarding the HCV association with breast cancer incidence. Population-based studies from HCV-endemic area demonstrated increased breast cancer incidence in HCV-positive women younger than 50 years. On the other hand, population studies from HCV-low prevalence regions failed to detect an association of the virus with breast cancer.

HCV seropositive patients constitute a large sector of oncology patients treated in Egyptian practice. HCV infection with or without clinically-significant liver disease impose several therapeutic, social and logistic problems. Recently, investigators from Mansoura University reported their findings among breast cancerpatients. According to these data, HCV-positive breast cancer patients had several markers of disease aggression such as large tumor size, high tumor grade and nodal infiltration. Moreover, HCV-NS4 (non-structural protein-4) blood levels positively correlated with the level of the known breast cancer marker CA15-3.

In the current study, the investigators will investigate the incidence of HCV seropositivity in breast cancer patients and an age-matched control group. The study also examines the association of HCV status on the patients' baseline characteristics such as tumor stage and grade and with patients' treatment plan and treatment outcome.

Specifically, the aims of the study are the following:

1. To test if HCV seropositivity is associated with breast cancer diagnosis in Egyptian population.
2. To test if HCV-positive patients harbour more aggressive breast tumors.
3. To test if HCV-positivity affects management decision in breast cancer patients.
4. To test if HCV-positive patients suffer more frequent adverse effects to breast cancer treatment.
5. To compare disease-free survival of HCV seropositive breast cancer patients vs. seronegative patients.

Association of Hepatitis C Virus With Breast Cancer

Association of Hepatitis C Virus Seropositivity With Breast Cancer Prognosis and Treatment Outcome

Percentage of patients with breast cancer with positive anti-HCV serological test.

The number of events related to breast cancer diagnosis. Disease-free survival (DFS) was calculated as the time from the date of breast cancer diagnosis to the date of last follow-up or the date of first breast cancer-related event. At the time of analysis, median survival has not been reached.

Mansoura University

Professor of surgery (surgical oncology)

All-cause Mortality and Adverse Events were not assessed in this retrospective, observational study

Study Group

Randomly selected data of 405 patients treated within the last ten years at the study site.

A historical control group derived from the raw data of a previously published study (PMID: 31463388, PMCID: PMC6709406, DOI: 10.1016/j.heliyon.2019.e02249)

Dakahlia Governorate Adult Female Population

Total

Age, Customized

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Egypt

Region of Enrollment

This is a retrospective study. Due to limited funding, a non-selected sample of Breast Cancer was compared to a historical control derived from the data of a previously published population study. Further studies are required.

Osama Hussein

Fisher exact test was used for testing of association of Breast Cancer diagnosis with anti-HCV test status.

Fisher exact test was used to test the association of Breast Cancer diagnosis with anti-HCV test result in women younger than 45 years.

One-hundred forty-five adult females from Dakahlia governorate were sampled in a published population-based cross sectional study from 2015 to 2017.

Prevalence of HCV Seropositivity in Breast Cancer Patients.

Anti-HCV Positive Patients

Anti-HCV Negative Patients

At the time of analysis, median survival has not been reached. This Outcome Measure was pre-specified to be collected only for the Study Group. The outcome is not applicable to the control group (non-cancer population).

Disease-related Events

One-hundred forty-five adult females from Dakahlia governorate were sampled in a published population-based cross sectional study from 2015 to 2017.

\[El-Ghitany EM, Farghaly AG (2019) Geospatial epidemiology of hepatitis C infection in Egypt 2017 by governorate. Heliyon 5 (8):e02249. doi:10.1016/j.heliyon.2019.e02249}

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Antiviral Agent HARVONI® for the Treatment of HCV-associated Indolent B-Cell Lymphoma	NCT03261349	Indolent Lympho...	Ledipasvir and ...	20 Years -	National Taiwan University Hospital
Sleep Apnoea Syndrome and Hepatocellular Carcinoma	NCT04190498	Sleep Apnea, Ob... Hepatocellular ... Non Alcoholic S...	Nocturnal oxime...	18 Years -	University Hospital, Grenoble
Association Between Hepatitis C Virus Infection and Hematologic and Thyroid Cancers	NCT00342641	Hepatitis C Vir...		-	National Institutes of Health Clinical Center (CC)
Hepatitis C Virus Detection in Oral Squamous Cell Carcinoma	NCT03109457	Hepatitis C	oral squamous c...	-	Cairo University
Association of Hepatitis C Virus With Breast Cancer	NCT04090164	Breast Cancer Hepatitis C		18 Years -	Mansoura University
Sleep Apnoea Syndrome and Hepatocellular Carcinoma	NCT04190498	Sleep Apnea, Ob... Hepatocellular ... Non Alcoholic S...	Nocturnal oxime...	18 Years -	University Hospital, Grenoble
Prediction of Incidence of Liver Cancer by Use of Real-time Tissue Elastography	NCT01360892	Chronic Hepatit... Chronic Hepatit...		20 Years -	Kindai University
The Second Multicenter Hemophilia Cohort Study	NCT00341705	Liver Decompens... Hepatocellular ... Non-Hodgkin Lym...		13 Years -	National Institutes of Health Clinical Center (CC)
The Second Multicenter Hemophilia Cohort Study	NCT00341705	Liver Decompens... Hepatocellular ... Non-Hodgkin Lym...		13 Years -	National Institutes of Health Clinical Center (CC)
Hepatitis C Virus Detection in Oral Squamous Cell Carcinoma	NCT03109457	Hepatitis C	oral squamous c...	-	Cairo University
Antiviral Agent HARVONI® for the Treatment of HCV-associated Indolent B-Cell Lymphoma	NCT03261349	Indolent Lympho...	Ledipasvir and ...	20 Years -	National Taiwan University Hospital
Prediction of Incidence of Liver Cancer by Use of Real-time Tissue Elastography	NCT01360892	Chronic Hepatit... Chronic Hepatit...		20 Years -	Kindai University
Telaprevir Plus Standard of Care (SOC) in HCV Associated Hepatocellular Carcinoma (HCC)	NCT01821963	Infection	Pegylated Inter... Ribavirin Telaprevir	18 Years - 69 Years	M.D. Anderson Cancer Center
Telaprevir Plus Standard of Care (SOC) in HCV Associated Hepatocellular Carcinoma (HCC)	NCT01821963	Infection	Pegylated Inter... Ribavirin Telaprevir	18 Years - 69 Years	M.D. Anderson Cancer Center
Association of Hepatitis C Virus With Breast Cancer	NCT04090164	Breast Cancer Hepatitis C		18 Years -	Mansoura University

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