Pegylated Alfa-2b Interferon Therapy of Patients With Hepatitis C-related Cirrhosis and High Liver Cell Proliferation (P02733/MK-4031-085)
Condition: Carcinoma, Hepatocellular
MeSH terms: Hepatitis C; Carcinoma; Carcinoma, Hepatocellular
Intervention: Peginterferon alfa-2b; Observation (no treatment)
Intervention description: Peginterferon alfa-2b, 50 μg, weekly, SC, for a period of 3 years.; No treatment was given to participants enrolled in the control arm (Arm B).
Intervention MeSH terms: Peginterferon alfa-2b
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 150.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This study aims to compare the role of peginterferon α-2b (50 μg/week) vs. control (no
      treatment) in the prevention of hepatocellular carcinoma, in adult patients with cirrhosis
      and initial signs of portal hypertension who did not respond to previous combined therapy
      with interferon alfa + ribavirin or peginterferon alfa + ribavirin or to interferon alfa
      monotherapy and with a high proliferation rate before entering the study. The duration of
      treatment will be 3 years, and the follow-up period will be 2 years.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Cirrhotic participants, both sexes, Child Pugh A, B, HCV-RNA positive, age < 70 years

          -  Participants non-responders to IFN + Ribavirin or PegIFN + Ribavirin or IFN
             monotherapy

          -  Pre-therapy liver biopsy (< 36 months) with PCNA-LI > 2.0

          -  Fibrosis score 5-6 (Ishak)

          -  Initial portal hypertension, such as gastroesophageal varices or one of the following
             US sign:

               -  Collateral circles

               -  Spleen longitudinal diameter > 12 cm

               -  Portal vein diameter at hilus > 12 mm

               -  Portal flow > 12 cm/sec

               -  Participants must have the following minimum hematologic and biochemical
                  criteria:

               -  Hemoglobin >= 11 g/dL

               -  Granulocyte count > 1,000/mm^3

               -  Platelets > 70,000/mm^3

               -  Prothrombin activity > 50%

               -  Total bilirubin <3 mg/dL

               -  Albumin >= 3.5 g/dL

               -  Serum creatinine within normal limits

          -  Uric Acid within normal limits

          -  Thyroid Stimulating Hormone (TSH), within normal limits

          -  Antinuclear antibodies (ANA) < 1:160

          -  Written informed consent

          -  Women of childbearing potential must have a negative pregnancy test

          -  Acceptance of patients of both sexes of proper contraceptive measures for the study
             period

        Exclusion Criteria:

          -  Pregnant or breast-feeding women

          -  Co-infection with HIV and/or HBV

          -  Autoimmune hepatitis or history of autoimmune disease

          -  Alcoholic liver disease

          -  Metabolic disease

          -  HCC

          -  Participants with liver and kidney transplants

          -  Evidence of decompensated liver disease such as history or presence of ascites,
             bleeding varices, spontaneous encephalopathy

          -  Chronic renal failure or creatinine clearance < 50 mL/min

          -  Pre-existing thyroid disease unless it can be controlled with conventional treatment

          -  History or presence of psychiatric condition, especially depression, or a history of
             severe psychiatric disorder, such as major psychoses, suicidal ideation and/or
             suicidal attempt

          -  Epilepsy and/or compromised central nervous system (CNS) function

          -  Significant cardiovascular dysfunction within the previous 6 months before the study
             starts (eg, angina, congestive heart failure, recent myocardial infarction, moderate
             or severe hypertension, significant arrhythmia)

          -  Hemoglobinopathies

          -  Poorly controlled diabetes mellitus

          -  Chronic pulmonary disease (eg, chronic obstructive pulmonary disease)

          -  Clinical gout

          -  Hypersensitivity to interferons or any component of the drug