Low-Dose Peginterferon and Ribavirin to Treat Chronic Hepatitis C in Patients Infected With HCV Genotype 2 or 3
Low-Dose Peginterferon and Ribavirin to Treat Chronic Hepatitis C in Patients Infected With HCV Genotype 2 or 3
This study will examine the effectiveness of low-dose peginterferon and ribavirin therapy for
 certain patients with chronic hepatitis C-a liver disease that, in some patients, can
 progress to cirrhosis of the liver, liver cancer, and liver failure.
Sixty patients with chronic hepatitis C infected with HCV genotype 2 or 3 will be treated
 using the combination of either low- or standard dose peginterferon and ribavirin for 24
 weeks, with re-treatment using the standard doses and a longer duration (48 weeks) for those
 who do not respond to or relapse after initial low dose therapy.

 Adult patients with chronic hepatitis C who have HCV genotype 2 or 3 and previously have not
 received anti-viral treatment will be given peginterferon alfa-2a (90 or 180 micrograms
 weekly by injection) and ribavirin (800 mg daily by mouth). Patients will be monitored at 2-
 to 4-week intervals for side effects, compliance, complete blood counts, liver biochemical
 tests and HCV RNA. Patients becoming HCV RNA negative by week 12 will be considered
 on-treatment responders, continue therapy to week 24, and be monitored thereafter for another
 24 weeks. Patients who do not become HCV RNA negative by week 12 as well as patients who
 relapse after therapy will be retreated with 180 micrograms of peginterferon weekly and 800
 mg of ribavirin for another 48 weeks.

 The primary outcome will be sustained loss of HCV RNA at 24 weeks after low- or standard-dose
 combination therapy. Secondary outcomes include viral kinetics and side effects. Because of
 preliminary results in the initial 31 patients enrolled in this study, the dose of
 peginterferon was changed from 90 to 180 micrograms weekly for the remaining 29 patients to
 be enrolled, allowing for a direct comparison of efficacy, viral kinetics and side effects of
 standard- vs low-dose peginterferon therapy.

 This study will evaluate the relative efficacy and safety of the standard versus lower doses
 of peginterferon with ribavirin in patients with chronic hepatitis C and HCV genotype 2 or 3.
-  INCLUSION CRITERIA:

 Age above 18 years, male or female.

 Presence of anti-HCV in serum.

 Positive HCV RNA determination in serum.

 HCV genotype 2 or 3 as determined by Inno LiPa assay or by direct sequencing. Patients with
 mixed genotypes will not be eligible if they have genotypes other than 2 or 3.

 Written informed consent.

 EXCLUSION CRITERIA:

 Previous treatment with interferon alpha or peginterferon.

 Decompensated liver disease, as marked by bilirubin greater than 4 mg/dL, albumin less than
 3.0 g/dL, prothrombin time greater than 2 sec prolonged, or history of bleeding esophageal
 varices, ascites or hepatic encephalopathy.

 Patients with ALT levels greater than 1000 U/L (greater than 25 times ULN) will not be
 enrolled but may be followed until three determinations are below this level.

 Pregnancy or, in women of child-bearing potential or in spouses of such women, inability to
 practice adequate contraception, defined as vasectomy in men, tubal ligation in women, or
 use of condoms and spermicidal, or birth control pills, or an intrauterine device.

 Significant systemic or major illnesses other than liver disease, including congestive
 heart failure, renal failure (creatinine clearance less than 50 ml/min), organ
 transplantation, serious psychiatric disease not controlled by psychotropic agents, and
 angina pectoris.

 Evidence of coronary artery disease or cerebral vascular disease, including abnormalities
 on exercise stress testing in patients with defined risk factors who will be screened for
 evidence of underlying coronary artery disease.

 Pre-existing, severe bone marrow compromise; anemia (hematocrit less than 30%), neutropenia
 (less than 1000 neutrophils/microliter) or thrombocytopenia (less than 70,000
 cells/microliter).

 History of hemolytic anemia.

 Evidence of another form of liver disease in addition to hepatitis C (for example hepatitis
 B, autoimmune liver disease, Wilson's disease, alcoholic liver disease).

 Active substance abuse, such as alcohol, inhaled or injection drugs within the previous six
 months.

 Evidence of hepatocellular carcinoma: either alfa-fetoprotein (AFP) levels greater than 50
 ng/ml (normal less than 9 ng/ml) and/or ultrasound (or other imaging study) demonstrating a
 mass suggestive of liver cancer.

 Clinical gout.

 HIV infection.

 Quiescent or active, serious autoimmune disease such as lupus erythematosus, ulcerative
 colitis, Crohn's disease or rheumatoid arthritis that in the opinion of the investigators
 might be exacerbated by therapy with alfa interferon.

 The use of immunosuppressive medications, including corticosteroids in doses of 10 mg of
 prednisone or its equivalent and higher.