Response to long-term lamivudine treatment in patients infected with hepatitis B virus genotypes A, B, and C

✍ Scribed by Mariko Kobayashi; Fumitaka Suzuki; Norio Akuta; Yoshiyuki Suzuki; Yasuji Arase; Kenji Ikeda; Tetsuya Hosaka; Hitomi Sezaki; Masahiro Kobayashi; Satomi Iwasaki; Junko Sato; Sachiyo Watahiki; Yuzo Miyakawa; Hiromitsu Kumada

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 207 KB
• Volume: 78
• Category: Article
• ISSN: 0146-6615
• DOI: 10.1002/jmv.20701

✦ Synopsis

Abstract

Response to lamivudine treatment longer than 1 year was compared in 15 patients persistently infected with hepatitis B virus (HBV) genotype A, 38 with genotype B, and 449 with genotype C. Patients with genotype A were younger (median age 37 [range 24–49] vs. 47 [24–67] or 44 [18–73], P = 0.015), possessed hepatitis B e antigen (HBeAg) more frequently (73% vs. 21% or 56%, P < 0.001) and HBV DNA in higher levels (8.6 [6.1–8.7] vs. 6.5 [<3.7–8.7] or 6.5 [<3.7–8.7] log genome equivalents (LGE)/ml, P = 0.024) than those with genotype B or C. During lamivudine, YMDD mutants (89% vs. 53% or 42%, P = 0.0001) and breakthrough hepatitis developed more often (47% vs. 21% or 29%, P = 0.023) in patients with genotype A than B or C. YMDD mutants elicited more frequently in patients with genotype A than B or C who were positive (82% [9/11] vs. 25% [2/8] or 48% [117/245], P = 0.037) or negative for HBeAg (75% [3/4] vs. 30% [9/30] or 33% [68/204], P = 0.003). HBeAg (hazard ratio 2.1 [95% confidence interval 1.53–2.92], P < 0.001) and genotype A (2.78 [1.08–7.12], P = 0.034) enhanced the emergence of YMDD mutants by the Cox proportional hazard model. The risk for breakthrough hepatitis was increased by the baseline alanine aminotransferase level <500 IU/L (2.56 [1.82–5.50], P = 0.018), HBeAg (2.11 [1.40–3.16], P < 0.001), cirrhosis (1.92 [1.24–2.97], P = 0.004) and HBV DNA ≥8.0 LGE/ml (1.57 [1.04–2.36], P = 0.03); it was influenced by genotypes only in patients with HBeAg. In conclusion, HBV genotypes help in predicting response to long‐term lamivudine treatment and development of YMDD mutants in patients with chronic hepatitis B. J. Med. Virol. 78:1276–1283, 2006. © 2006 Wiley‐Liss, Inc.