Clinical and virological characteristics of lamivudine resistance in chronic hepatitis B patients: A single center experience

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 × 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. J. Med. Virol. 75:391–398, 2005. © 2005 Wiley‐Liss, Inc.