INCLUSION CRITERIA
- Age 18 years or above, male or female
- Serum alanine or aspartate aminotransferase (ALT & AST) activities that are above the upper limit of normal (ALT greater than 41 or AST greater than 31 IU/L).
- Presence of anti-HCV in serum.
- Presence of HCV RNA genotype 1 in serum at levels above 10,000 copies/ml.
- Previous adequate therapy with interferon and ribavirin or peginterferon and ribavirin without a sustained virological response. An adequate course of therapy is defined as at least 12 weeks of interferon in doses of 3 million units three times weekly or peginterferon in doses of 180 micrograms for peginterferon alfa-2a or 1.5 micrograms/kg for peginterferon alfa 2b once weekly and ribavirin in starting doses of at least 1000 mg daily. Patients who initiated therapy at these doses, but required dose modification due to side effects will also be eligible.
- Written informed consent: Patients will be informed of the risk/benefits and side-effects of the medications used in this protocol and will be advised of the research blood drawn at each clinic visit. They will be given ample time to read the consent form and to ask any protocol related questions. Once this is done, the patient's signature will be obtained on the consent form to enroll them into the protocol.
EXCLUSION CRITERIA
- Evidence of other forms of liver disease.
- Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg) in serum.
- Primary sclerosing cholangitis as defined by liver histology.
- Wilson disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilson disease.
- Autoimmune hepatitis as defined by antinuclear antibody (ANA) of 3 EU or greater (ELISA) and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy for autoimmune hepatitis.
- Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency.
- Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. Patients with iron saturation indices of greater than 45% and serum ferritin levels of greater than 300 ng/ml for men and greater than 250 ng/ml for women will undergo genetic testing for C282Y and H63D.
- Drug induced liver disease as defined on the basis of typical exposure and history.
- Bile duct obstruction as suggested by imaging studies done within the previous six months.
- Decompensated liver disease, as marked by bilirubin greater than 4 mg/dl, albumin less than 3.0 gm/l, prothrombin time greater than 2 sec prolonged, Child-Pugh score of 7 or greater or history of bleeding esophageal varices, ascites or hepatic encephalopathy. Patients with ALT levels greater than 1000 U/L (greater than 25 times the upper limit of the normal range) will not be enrolled but may be followed until three determinations are below this level.
- Significant systemic or major illnesses other than liver disease, including congestive heart failure, coronary artery disease, cerebrovascular disease, pulmonary disease with hypoxia, renal failure, organ transplantation, serious psychiatric disease including depression, malignancy and any other conditions that in the opinion of the investigator would preclude treatment.
- Pre existing, severe bone marrow compromise; anemia (hematocrit less than 34%), neutropenia (less than 1000 polymorphonuclear cells/mm(3)) or thrombocytopenia (less than 70,000 cells/mm(3)).
- Any known diagnosis of hemolytic disorder.
- Serious autoimmune disease that, in the opinion of the investigators, might be worsened by interferon therapy, such as lupus erythematous, rheumatoid arthritis or Crohn's disease
- Known HIV infection.
- Active substance abuse, such as alcohol, inhaled or injection drugs within the previous one year.
- Pregnancy, lactation 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 spermicide, birth control pills/depot injection, or an intrauterine device.
- Evidence of hepatocellular carcinoma; either alpha-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.
- Immunosuppressive therapy with either corticosteroids (more than 5 mg of prednisone daily) or major immunosuppressive agents (such as azathioprine or 6-mercaptopurine).
- Consumption of SAMe or SAMe containing medication in the previous 6 months.
- Clinical gout at presentation.
- History of hypersensitivity reactions to S-adenosyl methionine.
- History of serious side effects leading to discontinuation of peg-interferon and/or ribavirin during the previous course of therapy.
- Serum creatinine greater than 1.5mg/dl in men and greater than 1.4 mg/dl for women.
- Any other condition, which in the opinion of the investigators, would impede the patient's participation or compliance in the study.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 09/15/2008