Gauthier J, Bourne E J, Lutz M W, Crowther L M, Dienstag J L, Brown N A, Condreay L D
Department of Virology, Glaxo Wellcome, Inc., Research Triangle Park, NC 27709, USA.
J Infect Dis. 1999 Dec;180(6):1757-62. doi: 10.1086/315147.
Hepatitis B viremia and emergence of hepatitis B virus (HBV) YMDD variants with reduced susceptibility to lamivudine were analyzed in patient sera from a phase II study of extended lamivudine therapy. Within 12 weeks, all patients exhibited a marked virologic response to lamivudine: >99% reduction (median 5 log decrease) in serum HBV DNA levels. Virus remained at >104 genomes/mL in 11 patients and decreased to <104 genomes/mL in the remaining 12 patients. In 10 patients, detectable YMDD variants emerged during the course of treatment. Six patients, including 3 with YMDD variants, experienced hepatitis B e antigen seroconversion while on lamivudine therapy or soon after its discontinuation. No patients with HBV DNA levels >104 genomes/mL seroconverted. Thus, patients who respond to lamivudine therapy with dramatic reductions in viral DNA level (to <104 genomes/mL) appear more likely to seroconvert than patients who do not achieve this level of HBV clearance.
在一项关于拉米夫定延长治疗的II期研究中，对患者血清进行分析，以检测乙肝病毒血症以及对拉米夫定敏感性降低的乙肝病毒（HBV）YMDD变异体的出现情况。在12周内，所有患者对拉米夫定均表现出显著的病毒学应答：血清HBV DNA水平降低>99%（中位数下降5个对数）。11例患者的病毒载量仍>104基因组/mL，其余12例患者的病毒载量降至<104基因组/mL。10例患者在治疗过程中出现了可检测到的YMDD变异体。6例患者，包括3例携带YMDD变异体的患者，在接受拉米夫定治疗期间或停药后不久出现了乙肝e抗原血清学转换。病毒载量>104基因组/mL的患者无血清学转换情况。因此，与未达到这种乙肝病毒清除水平的患者相比，那些对拉米夫定治疗有应答且病毒DNA水平显著降低（至<104基因组/mL）的患者似乎更有可能发生血清学转换。
