Long-Term Lamivudine Therapy for Chronic Hepatitis B

This study will evaluate the long-term safety and effectiveness of lamivudine therapy and the possibility of stopping therapy in patients whose hepatitis B is chronic, that is, long lasting, and which has responded to treatment. Chronic hepatitis B, caused by a virus, is a common form of liver disease affecting about 1 million Americans and about 5 percent of the world's population. Health effects include a continuous state of being infectious and the risk of transmitting hepatitis to other people, symptoms of liver disease, and development of cirrhosis-that is, severe damage to the liver-and liver cancer. Lamivudine is a medication that blocks hepatitis B effectively but does not make it disappear completely. Scientists believe that the immune system must also be active to rid the body of the last traces of hepatitis B.

Patients ages 18 and older who have chronic hepatitis B and are being treated with lamivudine may be eligible to participate in this study. They will undergo a medical history and physical examination and will be given lamivudine in 100 mg tablets to be taken as one tablet, once each day. Patients will be asked to return to the outpatient clinic every 3 months, when they will undergo a brief interview and measurement of vital signs-such as blood pressure, pulse, and body weight. During the visits, they will fill out questionnaires about any symptoms or side effects they have, and they will be seen by a doctor and have a brief medical history and examination. There will be a collection of blood for complete blood counts, liver enzymes, and hepatitis B virus. Extra blood tests may be done to analyze patients' immune reactions to hepatitis B. Patients will also receive refills of their lamivudine tablets. They will continue to be treated with lamivudine as long as it seems to control the hepatitis infection and liver disease.

At intervals of about 1 year, patients will have ultrasound examinations, lasting about 1 hour, of the liver and abdomen. Then at intervals of about 5 years, patients will undergo liver biopsies, which require a hospital stay of 2 to 3 days. A liver biopsy is done by passing a needle through the skin into the liver to obtain a piece of liver about 2 inches long and 1/16-inch in diameter. A small amount of bleeding probably occurs with most liver biopsies. Internal bleeding is a risk, which may require that the patient stay in the hospital a few days longer, for rest, observation and pain medicine. The biopsy provides information that proves whether lamivudine is controlling the liver disease and preventing it from worsening or progressing to cirrhosis.

Side effects of lamivudine include fatigue, muscle aches, fever and chills, sore throat, nausea, stomach pain or cramps, and diarrhea. Serious side effects are rare, occurring in less than 1% of people taking lamivudine. They include inflammation of the pancreas, nerve damage, and buildup of lactic acid in the blood. About 25% of patients experience a temporary worsening, or flare, of hepatitis during the first few months of treatment. If flares are severe, it is important for researchers to determine whether they are caused by resistance to lamivudine or by the immune system acting against the hepatitis B virus or another liver condition. A flare of hepatitis can also occur when lamivudine is stopped, that is, a withdrawal. In such situations, testing for hepatitis B virus levels and other liver conditions is important. It may lead to other treatments or stopping lamivudine and taking another medication instead. While patients are participating in the study, they will have a careful evaluation of their hepatitis and general condition. They may have an improvement in their disease as a result of long-term lamivudine therapy.