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

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.