GASTROENTEROLOGY LITERATURE ALERT!
LANDMARK ARTICLE - Required reading
| Dienstag JL, Schiff ER, Wright TL, et al. Lamivudine As Initial Treatment For Chronic Hepatitis B In The United States. N Engl J Med 1999;341:1256-63 |
Major Findings
First large trial in the U.S. looking at the efficacy of lamivudine for the treatment of chronic hepatitis B infections.
137 patients studied, lamivudine compared to placebo. Treatment course was 52 weeks (almost 1 year). Lamivudine dose was 100 mg orally once a day.
Histologic improvement was more likely in treated group: 52% vs. 32%
Suppression of HBV-DNA to undetectable levels was more common in the treatment group (44% vs. 16%), as well as normalization of ALT (41% vs. 7%)
HBeAG seroconversion was more common in the treated group (17% vs. 6%). About 32% lost HBeAG but did not develop HBeAB. Only one patient lost HBsAG
Side effects were comparable to placebo
FACTS TO REMEMBER FOR BOARDS
Lamivudine is a nucleoside analogue. It interferes with the reverse transcriptase present in HBV. Hepatitis C virus does not have a reverse transcriptase, so lamivudine is not effective for the treatment of hepatitis C infection
The goal of anti-viral therapy for hepatitis B is HBeAG seroconversion - the HBeAG becomes negative, the HBeAB positive. When that occurs, therapy may stop.
After one year of lamivudine therapy, about 15% have HBeAG seroconversion, with longer therapy, higher percentage seroconvert (up to 35% at 3 years)
Lamivudine therapy is associated with the emergence of lamivudine-resistant mutants, also known as YMDD mutations, the longer the therapy, the higher the risk.
YMDD mutants are associated with less hepatic inflammation and lower viral load and ALT levels, when they appear, treatment should continue to avoid re-appearance of the more pathogenic wild strain.
Most patients that have HBeAG seroconversion maintain that response for 16 weeks after stopping therapy
Clinical Application
Lamivudine is now an option for the initial therapy of hepatitis B infection. Compared to interferon, lamivudine-treated patients are less likely to become HBsAG negative, and the risk of YMDD mutants exist, which is not a problem with interferon. Which drug to use first is controversial. Combining both drugs does not appear to be better than either one alone.