We have investigated the characteristics of lamivudine-resistant strains in patients with chronic hepatitis B in Guangdong, China, where the predominant genotypes are B and C. Two hundred forty-seven patients treated with lamivudine in Nanfang Hospital were followed-up. Patients with hepatitis B e antigen (HBeAg) positive and hepatitis B virus (HBV)-DNA levels over 7.5 x 10(6) copies/ml at baseline had a shorter time to the selection of YMDD mutant (P = 0.02 and 0.00, respectively). The detection of YMDD mutant precedes HBV-DNA breakthrough and alanine transaminase (ALT) flare in about 2 and 3 months, respectively. The ALT flare after the appearance of YMDD mutants was more evident in HBeAg positive patients than HBeAg negative patients (P = 0.02). After emergence of YMDD mutant, the HBV-DNA level was significantly higher in genotype C patients compared with genotype B patients (P = 0.02). No significant difference of YMDD mutant pattern was found between patients with genotype B and C. Four kinds of new mutants were found in over two patients including rtL80I, rtG172E, rtG174C, and rtG172E/rtG174C. In vitro transfection and real-time analysis showed that rtG172E, rtG174C, and rtG172E/rtG174C mutants had a decreased replication competence compared with wild type (33%, 27%, and 15% of the wild type HBV, respectively). Our result suggest that genotypic monitoring of YMDD mutant is important for the management of patients treated with lamivudine.
2005 Wiley-Liss, Inc.