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