High-dose Ribavirin in Treatment of Chronic Hepatitis C Genotype 1 or 4 (VIRID)

Inclusion Criteria:

• hepatitis C genotype 1 or 4
• high viral load (>400000 IU/ml)
• indication for antiviral treatment or patient's desire for antiviral treatment
• hepatitis C treatment naive
• liver biopsy within 3 years of screening visit or when biopsy is contraindicated e.g in patients with clotting diseases or when a patient refuses to undergo a new biopsy in case the liver biopsy is older than 3 years, substitution by fibroscan is allowed.
• age 18-70 years

Exclusion Criteria:

• serum bilirubin >35 μmol/l
• albumin <36 g/l
• prothrombin time >4 sec prolonged
• platelets <90x109/l
• decompensated cirrhosis (Child-Pugh Grade B or C)
• hepatic imaging (ultrasound, CT or MRI) with the evidence of hepatocellular carcinoma (hepatic imaging should be performed within 3 months prior to screening for cirrhotic patients and within 6 months prior to screening for non-cirrhotic patients)
• alcoholic liver disease (indicator: MCV>100)
• obesity induced liver disease (indicators: steatosis proven by biopsy or ultrasound in association with a body mass index >30)
• drug related liver disease (indicator: positive history of hepatic toxic drug intake with a causal relation)
• auto-immune hepatitis (indicators: IgG >30g/l, anti smooth-muscle or antinuclear antibodies titer ³1:40)
• hemochromatosis (indicator: ferritin >1000 μg/l)
• Wilson's disease (indicator: ceruloplasmin (<0.2 g/l)
• alpha-1 antitrypsin deficiency (indicator alpha-1 antitrypsin <0.8 g/L)
• co-infection with hepatitis B virus or human immunodeficiency virus (HIV)
• any cardiovascular dysfunction (e.g. cardiac decompensation, myocardial infarction, present or history of arrythmia)
• other medical illness that might interfere with this study: significant pulmonary or renal dysfunction, malignancy other than skin basocellular carcinoma in previous 5 years, immunodeficiency syndromes (e.g.: steroid therapy, organ transplants other than cornea and hair transplant)
• contra-indications for peginterferon and/or ribavirin:
• severe psychiatric disorder, such as major psychoses, suicidal ideation, suicidal attempt and/or manifest depression. 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
• visual symptoms related to retinal abnormalities
• pregnancy, breast-feeding or inadequate contraception
• thalassemia, spherocytosis
• females who are pregnant or intending to become pregnant or male partners of females who are pregnant or intending to become pregnant
• absolute neutrophil count (ANC) <1.40x109/l
• hemoglobin (Hb) <7.5 mmol/l (female) or <8.1 mmol/l (male)
• serum creatinine concentration >1.5 times the upper limit of normal at screening
• substance abuse, such as I.V. drugs or alcohol (indicator: >28 drinks/week). 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 1 year
• 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