Short Course of Interferon Treatment in Patients With HCV Infection
Short Course of Interferon Treatment in Patients With HCV Infection
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.
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.
Inclusion Criteria:

 -  Adult males and non-pregnant females (more than 18 and less than equal to 50 years of
 age).

 -  Treatment naïve patients.

 -  Serological evidence of hepatitis C infection by an anti-HCV antibody test

 -  HCV PCR positive

 -  Genotype 3

 -  Absence of cirrhosis on liver biopsy.

 -  Absence of alcohol or drug abuse.

 Exclusion Criteria:

 -  Patients who do not consent to be included in the study.

 -  Pregnant or breast feeding females.

 -  Patients with a hemoglobin of <10g/dl, ANC <1500c/mm, and a platelet count <90000c/mm.

 -  Genotype non 3

 -  HCV PCR positive at the end of 4 weeks of treatment.

 -  Presence of cirrhosis on liver biopsy.

 -  Decompensated liver disease.

 -  History or other evidence of a medical condition associated with chronic liver disease
 other than CHC (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease,
 alcoholic liver disease, toxin exposure)

 -  History of having received IFN, PEG-IFN, RBV therapy previously.

 -  History of systemic antiviral therapy or investigational drug 3 months prior to the
 first dose of study treatment.

 -  Patients expected to need systemic antiviral therapy at any time during their
 participation in the study.

 -  Exceptions from the last two exclusion criteria are patients who have had a limited
 (less than 7 day) course of acyclovir or valacyclovir for herpetic lesions more than 1
 month prior to the first administration of trial treatment.