日本东京虎门医院（Toranomon）的小林真理子（Mariko Kobayashi）等报告，乙型肝炎患者中，病毒基因型为B型者对拉米夫定抗病毒治疗反应最佳，而A基因型者反应最差。
小林真理子等的研究共纳入了502例乙肝病毒（HBV）长期感染者，其中15例感染的HBV为A基因型，38例为B基因型，其余449例为C基因型，三组感染者年龄中位数分别为37岁、47岁和44岁。比较1年以上拉米夫定治疗对三组感染者的疗效。
结果显示，A基因型者乙肝病毒e抗原（HBeAg）阳性率显著高于B、C基因型者（分别为73%、21%和56%，P<0.001），前者HBV-DNA水平亦显著高于后两者（每毫升对数基因组当量分别为8.6、6.5和6.5，P=0.024）。在拉米夫定治疗过程中，A、B、C基因型者YMDD突变发生率分别为89%、53%和42%，反弹发生率分别为47%、21%和29%，A基因型者均显著高于后两者（P=0.0001，P=0.023）。A基因型者无论HBeAg阳性与否，YMDD突变引出率均高于B、C基因型者（P=0.037，P=0.003）。Cox比例危险模型分析显示，HBeAg阳性和A基因型可促使YMDD突变出现。
研究提示：检测HBV基因型，有助于预测慢性乙肝患者对拉米夫定长期治疗的反应性和YMDD突变的发生情况。对治疗应答较弱的A基因型患者，可考虑采用阿德福韦酯治疗，因为无论患者HBeAg是否阳性，后者均具有较好的疗效且不易导致耐药突变。
J Med Virol. 2006 Oct;78(10):1276-83.
Response to long-term lamivudine treatment in patients infected with hepatitis B virus genotypes A, B, and C.
Kobayashi M, Suzuki F, Akuta N, Suzuki Y, Arase Y, Ikeda K, Hosaka T, Sezaki H, Kobayashi M, Iwasaki S, Sato J, Watahiki S, Miyakawa Y, Kumada H.
Research Institute for Hepatology, Toranomon Hospital, Tokyo, Japan.
Research Institute for Hepatology, Toranomon Hospital, Tokyo, Japan.
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 > or =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.
发表于 2006-11-10 07:00
