Combination Therapy for Chronic Hepatitis B

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The summary below is from the full report titled "A Randomized, Controlled Trial of Combination Therapy for Chronic Hepatitis B: Comparing Pegylated Interferon-2b and Lamivudine with Lamivudine Alone." It is in the 15 February 2005 issue of Annals of Internal Medicine (volume 142, pages 240-250). The authors are H.L.-Y. Chan, N.W.-Y. Leung, A.Y. Hui, V.W.-S. Wong, C.-T. Liew, A.M.-L. Chim, F.K.-L. Chan, L.C.-T. Hung, Y.-T. Lee, J.S.-L. Tam, C.W.-K. Lam, and J.J.-Y. Sung.

What is the problem and what is known about it so far?

Hepatitis B is an inflammation of the liver that is caused by a virus. The virus spreads through contact with infected body fluids. Most people who get hepatitis B recover within a few months, but some develop chronic infection. Chronic infection increases risk for liver failure and liver cancer. Persons with chronic infection often have virus-related protein substances in their blood (called hepatitis B surface antigens and e antigens) for many years. Persons with hepatitis B e antigens may have very active liver disease and a high level of hepatitis B virus. Doctors often treat these patients with powerful antiviral drugs. However, some patients develop viral forms (mutants) that are resistant to 1 or more antiviral drugs. To help prevent resistance and improve outcomes, doctors sometimes combine 2 different types of antiviral drugs. Few studies have assessed the benefits and harms of these combination therapies for chronic hepatitis B.

Why did the researchers do this particular study?

To see whether combining pegylated interferon-2b with lamivudine reduces the amount of hepatitis B virus in the body and liver inflammation more than lamivudine alone.

Who was studied?

100 adults with chronic hepatitis B who had hepatitis B e antigens. The average age was about 33 years, and about two thirds of the patients were men. All patients had abnormal liver test results that suggested inflammation.

How was the study done?

The researchers recruited patients with chronic hepatitis B and elevated liver test results (an alanine transaminase level 1.3 to 5 times the upper limit of normal) from a single hospital in Hong Kong. They randomly assigned patients to receive pegylated interferon-2b for 32 weeks plus lamivudine for 52 weeks or lamivudine alone for 52 weeks. In the first group, interferon was given for 8 weeks before the lamivudine was started. Interferon was injected under the skin once weekly, and lamivudine was taken as a daily pill. The researchers asked patients about side effects and tested blood for evidence of virus, resistant mutants, and liver inflammation routinely during treatment and also 24 weeks after treatment ended.

What did the researchers find?

Tests at the end of treatment and 24 weeks after treatment showed that viral amounts were reduced more with combination therapy than with single therapy. Also, at the end of treatment, more patients who received single therapy had viral mutants resistant to lamivudine than patient who received combination therapy. Liver inflammation did not differ between the 2 groups. Patients who received combination therapy had more side effects, such as brief influenza-like symptoms and swelling at injection sites, than those who received single therapy.

What were the limitations of the study?

Patients assigned to combination therapy received treatment for 8 weeks longer than those assigned to single therapy. Both the researchers and the patients knew who received combination therapy.

What are the implications of the study?

Combining pegylated interferon with lamivudine may reduce viral amounts and viral resistance more than lamivudine alone in some patients with chronic hepatitis B who have hepatitis B e antigens.