Suzuki Fumitaka, Tsubota Akihito, Arase Yasuji, Suzuki Yoshiyuki, Akuta Norio, Hosaka Tetsuya, Someya Takashi, Kobayashi Masahiro, Saitoh Satoshi, Ikeda Kenji, Kobayashi Mariko, Matsuda Marie, Satoh Junko, Takagi Kimiko, Kumada Hiromitsu
Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan.
Intervirology. 2003;46(3):182-9. doi: 10.1159/000071460.
Several reports have examined the efficacy of long-term lamivudine therapy and the risk factors involved in emergence of viral resistance in Japanese patients with hepatitis B virus (HBV) infection. However, the patient cohorts in such studies are relatively small.
We analyzed 234 chronically HBV-infected Japanese patients who were treated with lamivudine for more than 12 months. They comprised patients with HBV genotype A (n = 8), genotype B (n = 21), genotype C (n = 203) and other HBV genotypes (n = 2).
In most patients, lamivudine resulted in normalization of alanine transaminase (ALT) levels at 6 and 12 months, and suppression of serum HBV DNA to undetectable levels by the branched chain DNA probe assay (bDNA). Rates of ALT normalization and non-detection of HBV DNA were higher among patients with genotype B than genotype C disease. The proportions of patients who achieved HBeAg loss were 27, 42 and 45% after 6 months, 1 year and 2 years, respectively. The emergence of mutations was not different among genotypes A, B and C by the Kaplan-Meier method. Multivariate analyses identified high HBV DNA level (bDNA >or=100 MEq/ml) as an independent factor associated with emergence of the YMDD motif mutation in all patients. Among patients with genotype C disease, which is the predominant HBV genotype in Japan, multivariate analysis also identified high HBV DNA level and HBeAg positivity as factors associated with emergence of resistance.
Patients exhibiting these factors at the commencement of lamivudine treatment must be monitored carefully at regular intervals for emergence of viral resistance.
多项报告探讨了长期拉米夫定治疗的疗效以及日本乙型肝炎病毒（HBV）感染患者出现病毒耐药的相关危险因素。然而，此类研究中的患者队列相对较小。
我们分析了234例接受拉米夫定治疗超过12个月的慢性HBV感染日本患者。他们包括HBV A基因型（n = 8）、B基因型（n = 21）、C基因型（n = 203）和其他HBV基因型（n = 2）的患者。
在大多数患者中，拉米夫定在6个月和12个月时使丙氨酸转氨酶（ALT）水平恢复正常，并通过分支链DNA探针分析（bDNA）将血清HBV DNA抑制到检测不到的水平。B基因型患者的ALT正常化率和HBV DNA未检出率高于C基因型疾病患者。实现HBeAg消失的患者比例在6个月、1年和2年后分别为27%、42%和45%。通过Kaplan-Meier方法，A、B和C基因型之间的突变出现情况没有差异。多变量分析确定高HBV DNA水平（bDNA≥100 MEq/ml）是所有患者中与YMDD基序突变出现相关的独立因素。在日本占主导地位的HBV C基因型疾病患者中，多变量分析还确定高HBV DNA水平和HBeAg阳性是与耐药出现相关的因素。
在拉米夫定治疗开始时表现出这些因素的患者必须定期仔细监测病毒耐药的出现。
