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.

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.