Subcutaneous Continuous Infusion of Interferon Alfa-2b and Ribavirin in Hepatitis C Genotype 1 Nonresponders

Inclusion Criteria: * Hepatitis C genotype 1 unresponsive to (peg)interferon /ribavirin therapy * In the past, peginterferon or conventional interferon plus ribavirin combination therapy for at least 12 weeks and less than 2-log HCV RNA decrease at week 12, HCV RNA positivity at week 24, breakthrough during therapy or relapse after therapy * At least 12 weeks between end of (peg)interferon/ribavirin therapy and start of high-dose IFN/ribavirin therapy * Persistent indication for antiviral therapy such as persistently elevated serum ALT or histological evidence of continuing or progressive fibrosis * Age 18-60 years Exclusion Criteria: * Signs of progressive liver disease since end of previous therapy, beyond generally accepted criteria for HCV antiviral therapy: * serum bilirubin \>35 μmol/l, albumin \<36 g/l, prothrombin time \>4 sec prolonged or platelets \<100,000/mm3 * decompensated cirrhosis (defined as jaundice in the presence of cirrhosis, ascites, gastric bleeding, esophageal varices or encephalopathy) * Hepatic imaging (US, CT or MRI) with the evidence of hepatocellular carcinoma (hepatic imaging should be performed within 3 months prior to screening) or an alpha fetoprotein \>50 ng/ml * Other acquired or inherited causes of liver disease that could explain liver disease activity * Co-infection with hepatitis B virus or human immunodeficiency virus (HIV) * Other significant medical illness that might interfere with this study: significant cardiovascular, pulmonary or renal dysfunction, malignancy other than skin basocellular carcinoma in previous 5 years, immunodeficiency syndromes (e.g.: HIV positivity, steroid therapy, organ transplants other than cornea and hair transplant) * History of a severe seizure disorder or current anticonvulsant use * History of thyroid disease poorly controlled on prescribed medications * Contra-indications for IFN and/or ribavirin: * Severe psychiatric disorder, such as major psychoses, suicidal ideation, suicidal attempt and/or manifest depression during previous (peg)interferon therapy. Severe depression would include the following: (a) subjects who have been hospitalized for depression, (b) subjects who have received electroconvulsive therapy for depression, or (c) subjects whose depression has resulted in a prolonged absence of work and/or significant disruption of daily functions. Subjects with a history of mild depression may be considered for entry into the protocol provided that a pretreatment assessment of the subject's mental status supports that the subject is clinically stable and that there is ongoing evaluation of the patient's mental status during the study * Reactivation of immunological disorders during previous therapy * Visual symptoms related to retinal abnormalities * Pregnancy, breast-feeding or inadequate contraception * Thalassemia, spherocytosis * Substance abuse, such as alcohol (³80 gm/day) and I.V. drugs. If the subject has a history of substance abuse, to be considered for inclusion into the protocol, the subject must have abstained from using the abused substance for at least 2 years * Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study