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发表于 2003-11-11 23:06
UPDATE-Hepatitis B Treatment
by Steven Han, MD
Assistant Clinical Professor
UCLA Division of Digestive Diseases
Dumont UCLA Liver Transplant Center
Chronic hepatitis B virus (HBV) is a global health problem, infecting an estimated 350 million people worldwide. High-prevalence areas include Asia, Southeast Asia, sub-Saharan Africa, South America, and the Middle East where over 8% of the population are carriers of HBV. In the United States, there are approximately 1.25 million chronic carriers of HBV, accounting for 17,000 hospitalizations and 5,500 deaths annually. Chronic HBV infection can lead to cirrhosis of the liver and is associated with a high risk for developing liver cancer.
Risk factors for acquiring chronic HBV infection include a history of multiple sexual partners, injection drug use, and blood transfusions in the remote past. Additionally, a family history of HBV infection or liver cancer, especially in persons of Asian, African, South American or Middle Eastern decent, should prompt screening for chronic HBV. Persons at high risk for acquiring HBV infection, including healthcare workers and family members of HBV infected persons, should be evaluated by their physician to determine if they require the hepatitis B vaccination to prevent HBV infection.
Currently, there are three medications approved by the Food and Drug Administration for the treatment of chronic HBV infection. The first medication approved was interferon-alfa2b, which is administered by subcutaneous injection. Take at a dose of 5 million units daily or 10 million units three times weekly for 12-24 weeks, viral suppression is achieved in about 33% with viral clearance (loss of HBsAg) seen in about 7%-8%. However, interferon therapy is associated with significant side effects including, fatigue, flu-like symptoms, depression, anorexia, hair loss, and mood swings.
The second medication approved for chronic HBV was lamivudine, which is taken orally once daily. At a dose of 100 mg daily for one year, viral suppression is achieved in 17%-32%. Lamivudine is very well tolerated with few significant side effects; however, long-term treatment with lamivudine can lead to the development of a lamivudine-resistant mutant HBV in about 14%-32%. The clinical implications of developing this lamivudine-resistant mutant are not known.
The third medication recently approved for chronic HBV is adefovir dipivoxil, which is also administered orally. At a daily dose of 10 mg for 1 year, viral suppression is achieved in 21%. There have been few side effect reported with adefovir dipivoxil, and to date, the use of adefovir dipivoxil has not been associated with the development of an adefovir-resisitant mutant. Adefovir dipivoxil may be considered as first-line treatment for chronic HBV, but has until recently been use predominantly in patients who failed lamivudine or in patients who have developed a lamivudine-resitant mutant.
Newer therapies for chronic HBV including medications such as entecavir, telbivudine (LdT), emtricitabine (FTC), and pegylated interferon are currently in clinical trials. Research in the area of chronic HBV is rapidly advancing, and the future holds promise that we will eventually eliminate this disease.
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