Pegylated Interferon to Treat Chronic Hepatitis D
Condition: Hepatitis D
MeSH terms: Hepatitis A; Hepatitis D; Hepatitis
Intervention: Peginterferon Alpha-2a
Intervention description: Treatment
Intervention MeSH terms: Peginterferon alfa-2a
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cirrhosis; Chronic Hepatitis; Alpha Interferon; Hepatitis D Virus; Delta Hepatitis; Viral Hepatitis; Antiviral Agents; Hepatitis D; HDV; Liver; Hepatitis

Summary:

      This study will evaluate the safety and effectiveness of a long-acting form of alpha
      interferon called pegylated interferon in treating hepatitis D virus (HDV) infection. HDV
      only infects people who already have hepatitis B infection. HDV is often severe and
      progressive. Alpha interferon is the standard treatment for HDV, given by injection once a
      day or three times a week for up to 12 months. However, this treatment does not work for
      everyone, and those who respond usually relapse when the drug is stopped. The
      sustained-release form of the drug, pegylated interferon, is given just once a week.
      Pegylated interferon is more effective than standard interferon in hepatitis C patients, with
      patients experiencing longer-term improvement. This study will evaluate the effects of
      pegylated interferon on hepatitis D and hepatitis B. It will determine whether long-term
      therapy with this drug improves inflammation and scarring of the liver, thereby delaying or
      reversing cirrhosis, and whether the improvement can be maintained.

      Patients with chronic hepatitis D over 6 years old may be eligible for this study.
      Participants will have a medical evaluation, including a history and physical examination,
      blood tests, routine urinalysis and 24-hour urine collection. Chest X-ray, electrocardiogram,
      abdominal ultrasound and liver biopsy will be done if these tests have not been done within
      the last year. In addition, depending on their age and individual health status, some
      patients may have exercise stress testing, an eye examination, hearing test, and psychiatric
      consultation. All patients will fill out a health-related quality of life questionnaire.

      Patients will receive pegylated interferon by injection once a week and have blood tests to
      measure the effects of treatment on the liver and on HBV and HDV levels. The medical
      examination and liver biopsy will be repeated at the end of 12 months. Patients who improved
      with treatment may continue therapy long-term. Medical evaluations and liver biopsies will be
      repeated at 3 years and at 5 years.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Age greater than or equal to 18 years, male or female

        Serum alanine or aspartate aminotransferase activities that are above the upper limit of
        normal (ALT greater than 41 or AST greater than 31 U/L) on an average of three
        determinations taken during the previous 6 months. The mean of the three determinations
        will be defined as 'baseline' levels.

        Presence of anti-HDV in serum.

        Evidence of chronic hepatitis on liver biopsy done within the previous 12 months with a
        necroinflammatory score in histology activity index of at least 5 (out of a maximum of 18)
        and at least 1 for hepatic fibrosis (out of a maximum of 6).

        Presence of HDV antigen in liver tissue.

        Written informed consent.

        Previous standard alpha interferon or other antiviral activity will not exclude patients.

        Active HBV replication will not exclude patients.

        All ethnicities.

        Patients will need to meet the first six entry criteria to enroll.

        EXCLUSION CRITERIA:

        Decompensated liver disease, as marked by bilirubin greater than 4 mg%, albumin less than
        3.0 gm%, prothrombin time greater than 2 sec prolonged, or history of bleeding esophageal
        varices, ascites or hepatic encephalopathy. Patients with ALT levels greater than 1000 U/L
        (greater than 25 times ULN) will not be enrolled but may be followed until three
        determinations are below this level.

        Pregnancy 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, or birth control pills, or an intrauterine device, or
        Depo-Provera, or Norplant.

        Significant systemic or major illnesses other than liver disease, including, but not
        limited to, congestive heart failure, renal failure (creatinine clearance less than 50
        ml/min), organ transplantation, serious psychiatric disease or depression (only if felt to
        be at high risk by the NIH psychiatric consultation service), and angina pectoris.

        Immunosuppressive therapy within the last 6 months.

        Evidence of another form of liver disease in addition to viral hepatitis (for example
        autoimmune liver disease, Wilson's disease, alcoholic liver disease, hemochromatosis, and
        alpha-1-antitrypsin deficiency).

        Any evidence of coronary artery disease or cerebral vascular disease, including
        abnormalities on exercise stress testing in patients with defined risk factors who will be
        screened for evidence of underlying coronary artery disease.

        Active substance abuse, such as alcohol, inhaled or injection drugs within the previous
        year.

        Evidence of hepatocellular carcinoma; either alphafetoprotein (AFP) levels greater than 200
        ng/ml (normal less than 9 ng/ml) and/or ultrasound (or other imaging study) demonstrating a
        mass suggestive of liver cancer.