The purpose of the research study is to evaluate a group of African Americans and Caucasians with hepatitis C virus infection, compare their response rates to treatment with a combination of pegylated interferon and ribavirin, and to identify possible causes for racial differences in response to therapy.

The purpose of this study is to identify causes for racial differences in response to therapy for treatment of the hepatitis C virus. This will involve examining differences between racial groups in the hepatitis virus, how the body processes the medications and the genetic make-up of persons. The patients will be taking standard treatment of hepatitis C - combination of pegylated interferon alpha 2b and ribavirin for either 24 or 48 weeks. Clinic visits and blood samples will be at study entry and 1, 2, 4 and 8 weeks after beginning treatment and then once a month until medication is stopped. Subjects will have clinic visits for 6 months after completion of therapy.

• Biological: Interferon
• Drug: Ribavirin

Inclusion Criteria:

1. Adult, male or female, African-American or Caucasian, age 18 or older and never been treated with interferon or ribavirin
2. Serum positive for hepatitis C virus by PCR or other assays (e.g. BDNA).
3. Liver biopsy prior to entry to this protocol with a pathology report confirming that the histological diagnosis is consistent with chronic hepatitis.

4. Compensated liver disease with the following laboratory parameters at the Entry visit:

   • Hemoglobin values of > 12 mg/dL for females or > 13 gm/dL for males
   • WBC > 3,000/mm3
   • Neutrophil count > 1,500/mm3
   • Platelets > 80,000/mm
   • Albumin > 3.0 g/dL or within 20% of LLN
   • Serum creatinine < 1.4 mg/dL
   • Thyroid Stimulating Hormone (TSH) within normal limits or thyroid disease under control
   • Reconfirmation and documentation that sexually active female patients of childbearing potential are practicing adequate contraception (intrauterine device, oral contraceptives, progesterone implanted rods (Norplant), medroxyprogesterone acetate (Depo-Provera), surgical sterilization, barrier method (diaphragm + spermicide), or monogamous relationship with a male partner who has had a vasectomy or is using a condom + spermicide) during the treatment period and for 6 months after discontinuation of therapy. A urine pregnancy test obtained at entry prior to the initiation of treatment must be negative. Female patients must not be breast-feeding. Documentation that sexually active male patients are practicing acceptable methods of contraception (vasectomy, use of a condom + spermicide, monogamous relationship with a female partner who practices an acceptable method of contraception) during the treatment period and for 6 months after discontinuation of therapy.
5. Written informed consent specific for this protocol has been obtained prior to entry.

Exclusion Criteria:

1. Hypersensitivity to alpha interferon or ribavirin.
2. Any cause for chronic liver disease other than chronic hepatitis C.
3. Hemoglobinopathies (e.g., Thalassemia) or any other cause of hemolytic anemia.
4. Evidence of advanced liver disease such as a history of or presence of ascites, bleeding varices, or spontaneous encephalopathy.
5. Any known preexisting medical condition that could interfere with the patient's participation in the protocol including: CNS trauma or active seizure disorders requiring medication; poorly controlled diabetes mellitus; serious pulmonary disease; immunologically-mediated diseases; gout or any medical condition requiring, or likely to require during the course of the study, chronic administration of steroids.
6. Patients with evidence of ischemia or stress testing, ECG evidence of ischemia, a significant arrhythmia, cardiac failure, recent coronary surgery, uncontrolled hypertension, angina or a myocardial infarction within 12 months. Pretreatment stress test will be required for all participants > 50 years of age.
7. Patients with clinically significant retinal abnormalities.
8. Substance abuse, such as alcohol (>80 gm/day), I.V. Drugs and inhaled drugs. If the patient has a history of substance abuse, to be considered for inclusion into the protocol, the patient must have abstained from using the abused substance for at least 1 year. Patients receiving methadone within the past year are also excluded unless a program of testing for continued substance abuse is initiated (testing at entry and then randomly at least every 2-3 months) and the patient is withdrawn from therapy for any violations.
9. Patients with a history of organ transplantation will be excluded.
10. Patients infected with Human Immunodeficiency Virus.
11. Preexisting psychiatric conditions; especially severe depression, or a history of severe psychiatric disorder, such as major psychoses, suicidal ideation and/or suicidal attempt are excluded. Patients with a history of mild depression may enter the protocol if they meet the following eligibility criterion and are monitored more intensively. Mild depression including either situational depression of a limited period or depressive symptoms, which do not significantly interfere with the patient's work or daily functions. Any patient with a manic element to his/her previous symptom complex will be excluded. All patients will complete the Center for Epidemiological Studies Depression Scale (CES-D). The CES-D is a 20-item self-report scale designed to measure depressive symptomatology experienced during the week prior to the interview. The items are scored on a four-point scale (0-3), with the total score ranging from zero to 60. CES-D scores of 16-20 suggest minor depression, and scores greater than 20 suggest major depression. The score can be determined in real time. A score of 16 or higher should prompt further questioning and consideration of treatment or referral to psychiatry. Detailed follow-up of each patient may be individualized according to his/her need; this would usually include predetermined visits.