About 85% of people who are infected by the hepatitis C virus (HCV) go on to develop chronic hepatitis C, which is defined by the presence of "persistent, detectable serum HCV RNA for a period greater than 6 months".

Chronic HCV infection has a variable course but usually includes many symptom-free years before complications such as cirrhosis, liver failure, and hepatocellular carcinoma develop. The specific HCV genotype is an important predictor of clinical outcome. Genotype 1 is the most common in the United States (75% of patients) and is associated with the poorest response to antiviral treatment.

The recommended regimen for patients who meet the criteria for antiviral treatment is dual therapy with "pegylated" interferon plus ribavirin (pegylated refers to the addition of polyethylene glycol to delay renal clearance). A sign that patients have responded to therapy is the elimination of the viral RNA from the serum - this is known as a viral response. A sustained viral response (SVR) is defined as the "absence of detectable HCV RNA from the serum in the six months after the end of therapy". Although a SVR is thought to result in decreased rates of important complications of chronic hepatitis C, dual therapy with pegylated interferon has not been available long enough to assess these clinical outcomes.

The "Drug Class Review on Pegylated Interferons for Chronic Hepatitis C Infection" compares the effectiveness and safety of two pegylated interferons: pegylated interferon alfa-2a (Pegasys) and pegylated interferon alfa-2b (PEG-intron). A summary of the findings is below.

How do pegylated interferons compare in treating chronic hepatitis C?

Data are limited, but indirect analysis suggests that there is no significant difference between the efficacy of peginterferon alfa-2a (Pegasys^®) plus ribavirin and alfa2b (PEG-intron^®) plus ribavirin in eliminating the hepatitis virus RNA from patients' serum. [full review]

Does the dose and duration of peginterferons alter their effectiveness in treating chronic hepatitis C?

No studies directly compared the effects of different doses or durations of the two pegylated interferons.

The optimal dose of peginterferon alfa-2b, when used as part of dual therapy with ribavirin, is 1.5 mcg/kg/week (the FDA-approved dose). No other dose has been shown to be more effective for achieving a SVR.

Studies comparing different doses of peginterferon alfa-2a have not been published. Almost all trials evaluated the FDA-approved dose of 180 mcg/week.

In patients with HCV genotype 1 infection, 48 weeks of dual therapy appears to be more effective than shorter courses. On the other hand, in patients with HCV genotype 2 or 3 infection, shorter courses may be sufficient. For example, in early responders to therapy, a 12 week-course of therapy appears to be as effective as 24 weeks. [full review]

Is one pegylated interferon safer or better tolerated than another, when given with ribavirin to treat chronic hepatitis C?

Indirect analysis does not show a significant difference in adverse events or the rate of withdrawal from clinical trials due to adverse events depending on whether pegylated interferon-alfa 2a or pegylated interferon-alfa 2b was used. Interpretation of the data is limited by differences among patients included in trials and inadequate reporting of results. [full review]

Are there any conditions for when one peginterferon is safer or more effective than another, when given with ribavirin to treat chronic hepatitis C?

There are almost no data to determine whether the efficacy or safety of peginterferons varies according to race, gender, age, presence of obesity, severity of baseline disease (e.g., higher viral loads, more severe fibrosis or inflammation) or other comorbid conditions (e.g., co-infection with HIV). [full review]

Drugs included in this review

Further information

This PubMed Clinical Q&A was reviewed by Susan Carson, MPH and Roger Chou, MD.

For the full report and evidence tables, please see:
Chou R, Carson S, Chan BKS, et al. Drug Class Review: Pegylated Interferons for Chronic Hepatitis C Infection: Final Report [Internet]. Portland (OR): Oregon Health & Science University; 2007 May. Available at: http://www.ncbi.nlm.nih.gov/books/NBK10662/.