The Therapeutic Effects of Lamivudine and Detection of Mutations in YMDD Motif of Hepatitis B Virus Genome in Chronic Hepatitis B Patients

Kim, Mi Sung; Chae, Hee Bok; Choi, Ki Won; Lee, Tae Won; Park, Seon Mee; Youn, Sei Jin; Bae, Suk Chul

Abstract

BACKGROUND/AIMS: Recipients, at 13 months after administration of daily doses of 100 mg of lamivudine, were likely to have the highest rate of HBeAg seroconversion (32%); the greatest suppression of HBV DNA (98% reduction at week 52); and the highest rate of sustained normalization of ALT levels (72%). In a 1-year trial of lamivudine for chronic hepatitis B patients, the incidence of YMDD mutations was known to be about 14%. We intend to determine the incidence of YMDD mutations and the correlation between the mutation of the virus and the clinical characteristics of the patient.
METHODS
Between Feb. 1999 and Sept. 2000 we conducted a prospective study. Patients received 100 mg of lamivudine per day orally for at least 9 months. The average period of follow-up was 15 months. The patients enrolled in this study were composed of 20 chronic hepatitis B patients and 3 liver cirrhosis patients. The male to female ratio was 18:5. The average age of the patients was 40 years. The HBV DNA was extracted from the initial serum and the serum on abnormal ALT level, and then PCR was done. Finally we sequenced a 459-bp fragment and analyzed which samples had YMDD mutation or did not.
RESULTS
(1) The genetic mutations in the YMDD locus occurred in 3 of the 23 patients (13%), two patients exhibited YIDD mutation, and one patient exhibited YVDD at 24, 52, 48 weeks of therapy respectively. (2) During the 3 months of treatment, serum ALT levels returned to normal in 13 of the 23 patients (56%). The HBV DNA disappearance rate at 3 and 8 months was 63% and 84% respectively. The 8 of 19 patients who lost the HBV DNA during lamivudine treatment experienced the breakthrough at about 13 months (the range: 8~27 months). 4 patients experienced HBeAg seroconversion during the treatment period (17%).
CONCLUSIONS
The mutations in the YMDD motif, especially the YIDD type, may aggravate the clinical outcome of the patients. We concluded that the treatment duration should be prolonged with these patients.