FibroScan in Patients With Hepatitis B and C Presenting for Liver Biopsy

Study Overview
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Brief Summary
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This study will examine the effectiveness of the FibroScan device in differentiating fibrosis in patients with hepatitis B and C. The FibroScan measures liver stiffness and will be correlated to the liver biopsy to see if it can diagnose the stage of liver disease. Patients who are scheduled to have a liver biopsy will also have a fibroscan and the stiffness will be correlated with the biopsy stage.

Detailed Description
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STUDY OBJECTIVES: Co -Primary Aims: Diagnosis of cirrhosis in patients with chronic viral hepatitis B and C; Correlation of the FibroScan measurement with Metavir liver fibrosis scores by differentiating no/mild fibrosis (F0-F1) from severe fibrosis (F2-F4). STUDY DESIGN: This is a multi-center study in which the FibroScan measurements will be collected prospectively from patients with chronic hepatitis B and C virus presenting for liver biopsy. The study duration will be 12 months. The study will initially have 3 investigational sites in the United States. Up to 3 more investigational sites may be identified to participate in the trial. Study Sites: Initially the following three sites will participate in the trial: Duke University Medical Center, Durham, NC: Keyur Patel, M.D.; Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA: Nezam H. Afdhal, M.D.; St. Louis University, St. Louis, MO: Bruce R. Bacon M.D. Study Population: Subjects with chronic liver diseases secondary to chronic hepatitis C and hepatitis B, undergoing a liver biopsy as the standard of care for their disease, will be eligible for the study. Subjects with hepatitis C, co-infected with other infectious viral diseases, such as hepatitis B or HIV-1, or both, may also be candidates for study enrollment provided the inclusion/exclusion criteria are met. The subjects must be scheduled for liver biopsy either prior to treatment (treatment naïve) or, if previously treated, they must have been off treatment for at least three (3) months. The time between the date of the FibroScan reading and the date of biopsy must not exceed six (6) months. Sample Size: A total of at least 300 evaluable patients (males and females) will be enrolled in this study. Enrollment will be considered competitive with no site enrolling more than 50% of the study population. Sample size is based on a prevalence of 20% cirrhosis. Subject Inclusion Criteria: Subject is able to give informed consent for this study and agrees to provide a blood sample. Subject must be at least 18 years of age. Subject has had or will have a liver biopsy for chronic liver disease, secondary to HBV or HCV or within 6 months of FibroScan (experimental cohort 1 only). Subjects who have hepatitis C (HCV) or hepatitis B (HBV) should be treatment naïve or off interferon therapy or nucleoside/nucleotide analogs for HBV for a minimum of 3 months prior to the FibroScan and liver biopsy. Subject Exclusion Criteria: Unable or unwilling to provide informed consent. Confirmed diagnosis and/or history of malignancy, or other terminal disease. Uninterpretable biopsy specimen. Missing critical clinical, biochemical and/or demographic information. Receiving anti-viral therapy for infection of HCV or HBV within 3 months prior to the FibroScan and liver biopsy. Subject with other chronic liver disease, including Wilson's disease, alpha 1-antitrypsin deficiency, cholestatic liver disease, or hemochromatosis. Patient with clinical ascites Patients with morbid obesity defined as a body mass index (BMI) of greater than or equal to 40. Patients who are pregnant Patients who have an implantable cardiac device such as defibrillator or pacemaker SAMPLE REQUIREMENTS and TESTING: A minimum of 8 valid measurements will be obtained for each subject from the right lobe of the liver. The tip of the probe transducer will be covered with coupling gel and placed on the skin, between the ribs at the level of the right lobe of the liver. The operator, assisted by an ultrasonic time motion image, will locate a portion of the liver that is at least 4cm thick and free of large vascular structures. The depth of measurement will be between 25 mm and 65 mm. During the acquisition subjects will lie on their back with the right arm behind the head, in a similar position to that used for liver biopsy. The physician will take the measurements with the probe placed in the intercostal space. The median value of the estimates will be kept as the elasticity value of the liver for a given patient. The entire examination should last approximately 5 minutes.

Official Title
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Comparison of FibroScan With Histological Evaluations of Liver Fibrosis in Patients With Hepatitis B and C Presenting for Liver Biopsy

Conditions
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Cirrhosis, Hepatitis B, Hepatitis C

Intervention / Treatment
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* Device: FibroScan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is able to give informed consent for this study and agrees to provide a blood sample. Subject must be at least 18 years of age. Subject has had or will have a liver biopsy for chronic liver disease, secondary to HBV or HCV or within 6 months of FibroScan (experimental cohort 1 only). Subjects who have hepatitis C (HCV) or hepatitis B (HBV) should be treatment naïve or off interferon therapy or nucleoside/nucleotide analogs for HBV for a minimum of 3 months prior to the FibroScan and liver biopsy. Exclusion Criteria: Unable or unwilling to provide informed consent. Confirmed diagnosis and/or history of malignancy, or other terminal disease. Uninterpretable biopsy specimen. Missing critical clinical, biochemical and/or demographic information. Receiving anti-viral therapy for infection of HCV or HBV within 3 months prior to the FibroScan and liver biopsy. Subject with other chronic liver disease, including Wilson's disease, alpha 1-antitrypsin deficiency, cholestatic liver disease, or hemochromatosis. Patient with clinical ascites. Patients with morbid obesity defined as a BMI of greater than or equal to 40. Patients who are pregnant. Patients who have an implantable cardiac device such as defibrillator or pacemaker.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm undergoing FibroScan<br>Single arm active comparison of biopsy to vibration controlled elastography | Device: FibroScan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnosis Performance of VCTE for Determination of Cirrhosis (Metavir F4) in Patients With Chronic Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) | VCTE was used to diagnose cirrhosis F4 in 748 patients undergoing liver biopsy and VCTE within a 28 day time period. | 28 days | 
| Diagnostic Accuracy of VCTE for the Prediction of Metavir Fibrosis Scores by Differentiating no/Mild (F0/F1) From Severe Fibrosis (F2 - F4) | 95% CI for Metavir Fibrosis stage 0 -1 consistent with no or mild fibrosis compared to Metavir 2 - 4 which represents significant fibrosis or cirrhosis | Liver Biopsy and VCTE within a time frame of 6 months |