Ignite Creation Date:
2024-05-05 @ 11:51 AM
Last Modification Date:
2024-10-26 @ 9:14 AM
Study NCT ID:
NCT00152880
Status:
UNKNOWN
Last Update Posted:
2005-12-01
First Post:
2005-09-08
Brief Title:
Apoptosis and Hepatitis B The Role of Apoptosis in Patients Who Are HBeAg Negative
Sponsor:
University Health Network Toronto
Organization:
University Health Network Toronto
Study Overview
Official Title:
Apoptosis and Hepatitis B The Role of Apoptosis in Patients Who Are HBeAg Negative Have Normal ALT and HBV DNA 10000 CopiesmL
Status:
UNKNOWN
Status Verified Date:
2005-09
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
A large number hepatitis B surface antigen positive individuals are HBeAg negative with normal liver tests Historically such patients were thought to have suppressed viral replication and were considered to be at low risk for complications With the use of more sensitive technology physicians are now able to identify a group of patients who are HBeAg negative have normal liver enzymes and detectable HBV DNA Some of these patients develop signs of liver inflammation and fibrosis on biopsy We intend to investigate whether normal programmed cell death apoptosis plays a role in causing the silent liver injury in this group of patients In other words the purpose of this study is to see whether apoptosis may be responsible for the silent liver death and injury that occurs in these so called inactive carriers who are HBeAg negative have normal serum ALT values and HBV DNA 10000 copiesmL In this study the liver biopsies would be routinely collected in the clinic and investigated for the evidence of inflammation and fibrosis and special testing would be performed to detect for evidence of apoptosis Around 30 patients from UHN would be participating in this study This study will test the hypothesis that subjects who are HBeAg negative have normal ALT and have HBV DNA 10000 copiesmL will demonstrate an increased rate of apoptosis in liver tissue compared to healthy age-matched controls If this hypothesis is confirmed it will imply that the previous assumption that this group of patients has inactive disease is false and would implicate apoptosis as an important mechanism responsible for causing liver damage If apoptotic activity is indeed elevated further study of these pathways could potentially yield therapeutic interventions to inhibit apoptosis
Detailed Description:
Through a retrospective chart review patients with HBsAg who are HBeAg negative have normal ALT and HBV DNA 10000 copiesmL and who have or who are about to undergo liver biopsy will be identified These individuals will be patients at the Toronto Western Hospital Liver Clinics Inclusion criteria1 HBsAg positive2 Stable HBeAg status for at least one year prior to biopsy3 Normal ALT levels defined as 15 x the upper limit of normal for at least 90 days prior to biopsy4 HBV DNA 10000 copiesmL by PCR measured within 90 days of liver biopsyExclusion criteria1 Coinfection with viral hepatitis A C or D2 Coinfection with HIV3 Presence of Hepatoma4 Known presence of other malignancy5 Previous antiviral treatmentThe diagnosis of hepatitis B will be based on standard serological assay results and HBV DNA detected with polymerase chain reaction using the Cobas Amplicor HBV Monitor Test Roche Diagnostics inc This testing is part of the usual blood work regularly performed on these patientsWe intend to stain the liver biopsies for quantitative assessment of apoptotic activity using three staining techniques1 TUNEL2 Immunohistochemistry for activated caspase-3 caspase-9 and cytochrome-C release3 Western blotting for caspase 3678 and 9 Liver biopsies will only be performed if clinically indicated independent of this study protocolAt the time of liver biopsy liver tissue waswill be buffered in formalin and embedded in paraffin Tissue will also be frozen at minus 80 degrees for Western blotting Two age-matched control groups of patients will also be randomly selected and compared to the study population These control liver biopsies will be stained for apoptotic activity and for disease activity as well These control groups will include patients who are1 HBeAg negative unstable elevated ALT2 Healthy controls living donor biopsies All sections will be assessed for apoptotic activity using the appropriate technique that is specific for TUNEL immunohistochemistry and Western blotting respectively Liver histology will also be reviewed for grade and stage by an experienced hepatopathologist at the UHN Necroinflammatory activity will be assessed using Ishaks hepatitis activity index and the Laennec grading system a minor modification of the METAVIR system will be used for assessment of hepatic fibrosis Liver cell apoptosis assessed by the various techniques will be reported for the study group and the control groups as means - SEM To compare the means between groups ANOVA or Students t test will be performed Pearsons correlation coefficient will be used to measure the degree of association between apoptosis and histopathological activity on liver biopsy Only the principal investigator will have access to personal and demographic information relating to the individuals included Those performing pathological review and statistical analysis will be blinded to patient information
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None