Chronic Hepatitis C Non-Responder Study With AdoMet and Betaine

Inclusion criteria

• Male and female between 18 and 65 years.
• Non-responders in previous treatments with IFNα plus ribavirin or pegylated IFNα plus ribavirin.
• Elevated ALT-levels on at least two occasions during >6 months preceding entry.
• Detection of HCV RNA in serum (PCR).
• Compensated liver disease (Child-Pugh A) and a Child-Pugh score <5.
• The following minimal hematologic and biochemical criteria:
• Hemoglobin for males and females >11g/dl
• Absolute Neutrophil count >1500 cells/mm3
• Platelets >75'000/mm3
• HBs Ag negative.
• ANA <1:320, and no evidence for autoimmune hepatitis.
• α-Fetoprotein <50μg/l (when between upper limit of normal and 50μg/l, ultrasonographical exclusion of hepatocellular carcinoma (HCC) is needed).
• Fasting blood glucose within normal limits, if history of diabetes or hypertension, a pre-therapy ocular examination is indicated.
• TSH within normal limits or adequately controlled.
• Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 2-3 week period prior to the first dose of study drug. Additionally, all fertile males and females must be using effective contraception during treatment and during the 6 months after treatment end. This may include, but is not limited to, using birth control pills, IUDs, condoms, diaphragms, or implants, being surgically sterilized, or being in a post-menopausal state.
• Willingness to give written informed consent and willingness to participate to and comply with the study

Exclusion criteria

• Women with ongoing pregnancy or breast feeding.
• Positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, HBe Ag.
• Positive test at screening for HIV.
• History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures).
• Hypersensitivity to study drugs.
• Participation in any other clinical trial within 30 days of entry into this protocol.
• Treatment with any investigational drug within 30 days of entry into this protocol.
• History or evidence of decompensated liver disease (Child-Pugh B/C) and a Child-Pugh score >5. Ascites, coagulopathy, hyperbilirubinemia, hepatic encephalopathy, or hypoalbuminemia and a Child-Pugh score >5 are conditions consistent with decompensated liver disease.
• History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease.
• Hepatocellular carcinoma (HCC) or α-Fetoprotein >50μg/l.
• Patients with organ transplants other than cornea and hair transplant.
• Therapy with any antisystemic or immunomodulatory treatment (including supra-physiologic doses of steroids or radiation) <6 months prior the first dose of study drug
• Hemoglobinopathy (e.g. thalassemia) or any other cause of or tendency for hemolysis.
• Any known preexisting medical condition that could interfere with the patient's participation in and completion of the study such as:
• Preexisting psychiatric condition, especially depression, or a history of severe psychiatric disorder, such as major psychosis, suicidal ideation and/or suicidal attempts (based on a mandatory psychiatric advice).
• CNS trauma or active seizure disorders requiring medication.
• Significant cardiovascular dysfunction.
• Poorly controlled diabetes mellitus.
• Renal dysfunction, i.e. serum creatinine levels >1.5 times upper limit of normal.
• Autoimmune diseases.
• Evidence of severe retinopathy (e.g. CMV retinitis, macular degeneration).
• Any medical condition requiring, or likely to require during the course of the study, chronic systemic administration of steroids.
• Clinical gout.
• Important substance abuse (alcohol >80 g/d, i.v. drugs etc.).
• Active opportunistic infections.
• Non-Hodgkin lymphoma or Hodgkin lymphoma.
• Kaposi sarcoma.
• Inability or unwillingness to provide informed consent or abide by the requirements of the study.
• Male partners of pregnant women.