Journal Club

Peginterferon and Ribavirin Therapy in Hepatitis C

brought to you by

Instructions

  Take Another Course

Post-Test

Resources

Treating hepatitis quickly is very important to treatment success. Unless the patient’s body has fought off the infection by itself, treatment may be needed to control chronic hepatitis C infection. Sometimes, the treatment takes a long time to work, and sometimes it may not help. But because this disease can get worse over time, it is very important that the patient seek proper treatment and care. It is also crucial to monitor treatments for adverse events and compliance to assure the best possible outcomes.

The goal of treatment for hepatitis is to reduce the virus load early to prevent its progression to serious, end-stage liver disease.

The current approach to treating chronic hepatitis C is combination therapy with a pegylated alpha interferon (peginterferon) and ribavirin. Peginterferon is indicated for use alone or in combination with ribavirin for the treatment of chronic hepatitis C in patients not previously treated with interferon alpha that have compensated liver disease and are at least 18 years of age. Early diagnosis and treatment are crucially important. While there is no guaranteed cure for chronic hepatitis B or C, a significant percentage of people who are treated in this manner improve.

Pegylation is a process whereby a substance called polyethylene glycol (PEG) is attached to a protein in order to extend protein activity. PEG is used in everyday products, such as foods and cosmetics. When used in prescription medications, active substances stay in the body longer before they are broken down and eliminated.

Interferon was developed in its alfa-2b form as the first FDA-approved therapy for hepatitis C. Now with pegylated interferon, the interferon stays in the body longer to help maximize treatment outcomes. Standard unmodified interferon only stays in the body for about a day. Pegylated interferon provides longer, more constant drug levels to better suppress the hepatitis C virus. Pegylated interferon also allows for once-weekly dosing, compared to dosing three times a week with standard unmodified interferon. This can mean fewer shots over the course of treatment. In fact, patients on pegylated interferon can experience 2/3 less (104 fewer) injections over a one-year treatment course.

The most common adverse events associated with pegylated interferon are "flu-like" symptoms which have been reported in approximately 50% of patients, which may decrease in severity as treatment continues. Application site disorders are common (47%), but are mild (43%) or moderate (4%), and include injection site inflammation and reaction (i.e., bruising, itchiness, irritations). Injection site pain is also reported in 2% of patients receiving pegylated interferon. Alopecia (thinning of the hair) is another often reported side-effect of therapy with alpha interferons including pegylated interferon.

Ribavirin is given orally and used in combination with interferon therapy. The most common side effect associated with ribavirin therapy is anemia. Other side effects include neutropenia, thrombocytopenia, myocardial infarction (associated with low red cell count), and severe birth defects. Caution should be taken in patients with known heart disease. Both male and female patients should use effective contraception to prevent accidental pregnancy.

Anemia associated with ribavirin therapy can negatively impact quality of life through increased fatigue, and is frequently relieved by decreasing ribavirin dosing. Epoetin alfa has been shown to relieve many of the symptoms related to chronic anemia in a number of cancer chemotherapy studies, and in a preliminary report from patients undergoing hepatitis C therapy.³ Neutropenia tends to be induced to a greater degree with peginterferon therapy than with unmodified therapy putting the patient at greater risk of infection when neutrophil counts fall below 500 cells/mm.⁴ And although rapid decreases in neutrophil counts can be seen within the first couple of weeks after initiation of therapy, they tend to stabilize over the next four weeks of therapy. Once therapy is discontinued, neutrophil levels quickly return to baseline. Current practice calls for a peginterferon dose reduction when neutrophil counts fall below 750 cells/mm, but there is some debate as to this number as a starting point for dose reductions.⁵ Thrombocytopenia has also been seen in this population, but it is in rare. Rare instances of autoimmune thrombocytopenic purpura have been seen with peginterferon therapy, but in such instances platelet counts should be investigated for their role in autoimmunity. Depression is seen in approximately 20-30% of patients undergoing peginterferon and ribavirin therapy. Quality of life is affected, and is often relieved through dose reduction or discontinuation. Of note in the Fried et al. study in this Journal Club, depression was reported less frequently in patients receiving peginterferon than those receiving unmodified interferon. Also of note, most cases of peginterferon-induced depression are deemed mild to moderate, and can be successfully managed through the use of antidepressants.⁶