Short Course of Interferon Treatment in Patients With HCV Infection
Condition: Hepatitis C; Chronic Disease; Treatment
MeSH terms: Hepatitis C; Hepatitis; Chronic Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      To determine if a shorter course of interferon and ribavirin therapy will be sufficient in
      carefully selected patients with chronic hepatitis C virus genotype 3 infection, as compared
      to the standard length of treatment of 6 months.
    

Detailed description: 
      1. INTRODUCTION

           1.1 Hepatitis C Hepatitis C Virus (HCV) is a major cause of chronic hepatitis and
           hepatic fibrosis1. Acute infection advances to chronicity in up to 80% of patients,
           which can further progress to cirrhosis and hepatocellular carcinoma in a significant
           number1.

           Hepatitis C is a global problem, prevalent in industrialized as well as in the
           developing world2. It is a major cause of chronic liver disease (CLD) in Pakistan and
           has surpassed hepatitis B as the single most important cause for cirrhosis and
           hepatocellular carcinoma (HCC) in Pakistan 3.

           1.2 Study Medications A combination of interferon and ribavirin therapy has been the
           standard of care world-wide for the past few years1, 2. Standard treatment duration is
           for 24 weeks for genotype non 1, and 48 weeks for genotype 12.

           1.2.1 Interferon Alfa 2a Interferon Alfa was the first drug shown to have bioactivity
           against HCV. Combining ribavirin with interferon Alfa was found to be more effective
           than interferon Alfa mono-therapy in previously untreated patients as well in patients
           who relapsed after one or more courses of interferon Alfa therapy2.

           1.2.2 Ribavirin Ribavirin is a guanosine analogue that inhibits the in vitro replication
           of a wide range of RNA and DNA viruses1. The mechanism of antiviral activity is not
           fully defined, although it may involve alteration of cellular nucleotide pools and
           inhibition of viral RNA synthesis1, 4. Ribavirin monotherapy has little or no effect on
           the replication of HCV but can result in normalization of serum ALT activity and
           improvement in liver histology. However, relapse occurs in nearly all patients treated
           with ribavirin alone1.

           Combining Ribavirin with Interferon has been found to be more effective than Interferon
           monotherapy in the treatment of chronic hepatitis C. In a large clinical trial of 1121
           patients, a sustained virological response (SVR) was achieved in 53% of patients treated
           with Interferon plus Ribavirin as compared to 29% of patients treated with Interferon
           alone1, 4.

        2. RATIONALE Most treatment related studies on HCV have come from the West, where the most
           prevalent genotype is 1; their results however do not necessarily reflect the outcome in
           a developing country like Pakistan, where studies have already confirmed that the most
           prevalent genotype is 32. Success rates have globally been reported to be high when
           treating genotype 3: it has long been observed that patients infected with genotype 2
           and 3 respond better to interferon therapy than patients infected with genotype 11, 3.

           Favorable prognostic factors have been identified which predict a better response to
           therapy in the treatment of chronic HCV. These include:

             -  Younger age

             -  Genotype 3

             -  No cirrhosis on liver biopsy, and

             -  Absence of alcohol or drug abuse1, 7.

           Few studies have investigated the efficacy of a short course therapy for patients with
           favorable predictive factors; most of these studies have used interferon monotherapy4,
           5, while others have used a combination treatment for shorter duration in relapsed
           patients6. There is evidence that combination treatment may be beneficial when used as
           induction therapy, followed by interferon in a short course program, 7. Cases infected
           with HCV genotype 3 being treated for as little as 4-12 weeks and remaining sustained
           responders have been reported8

           Since HCV genotype 3 responds so well to a combination of interferon and Ribavarin, it
           has been suggested that this patient population may have a similar response to a shorter
           duration of therapy7, 8, 9. The efficacy of a short course interferon and Ribavarin
           combination therapy compared to a longer course of therapy has not been compared in the
           treatment of patients with favorable predictive factors.

           2.1 Rationale for Dosage Selection

           1.2.2.1 Interferon Alfa 2a The dose chosen for interferon Alfa 2a (3 million units
           thrice weekly, sc) is the dose currently approved in Pakistan for combination therapy
           with ribavarin1.

           1.2.2.2 Ribavarin The dose chosen for Ribavarin (800-1200 mg per day) is the dose
           currently approved in Pakistan for combination therapy with interferon in patients with
           HCV.1

        3. HYPOTHESIS In patients with chronic hepatitis C infection with favorable predictive
           factors for treatment, a short course of combination therapy with interferon and
           Ribavarin is equally efficacious as the longer course of treatment.

        4. OBJECTIVE To determine whether 16 weeks of interferon and Ribavarin therapy is as
           effective as 24 weeks of therapy in achieving sustained virological response in patients
           with favorable predictive factors who are infected with HCV genotype 3.

        5. SIGNIFICANCE Pakistan has an enormous burden of chronic HCV infection. The cost of
           treatment is prohibitive and is unaffordable for a large proportion of our population2,
           3. A short course therapy comparable to the standard regimen would have significant
           implications; a striking decrease in financial burden on the health care system of the
           country, as well as the patients and a reduction in patient exposure to both
           medications, resulting in decreased treatment related adverse effects. In addition a
           larger number of patients will be able to afford the treatment due to a decrease in
           treatment duration and in turn the overall cost.
    

Intervention name(s): 16 weeks Interferon Tiw with Ribavirin; 24 weeks Interferon
Intervention type(s): Drug; Drug
Intervention description(s): 16 weeks Interferon Tiw; 24 weeks Interferon Tiw with Ribavirin
Other intervention name(s): Uniferon; Uniferon
Intervention MeSH terms: Interferons; Ribavirin; Iron-Dextran Complex
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chronic HCV; Treatment