拉米夫定对湖北地区乙型肝炎病毒基因型的影响

目的研究拉米夫定对湖北地区乙型肝炎病毒基因型的影响及其临床意义。方法采用多对型特异性引物-聚合酶链反应检测160例慢性乙型肝炎患者血清HBV基因型;采用基因芯片技术对86例拉米夫定治疗18个月的慢性乙型肝炎患者进行酪氨酸—蛋氨酸—天冬氨酸—天冬氨酸(YMDD)基序、G1896A、A1814C、A1792T和G1764A单碱基变异检测。结果160例慢性乙型肝炎患者,B基因型127例(79%),C基因型24例(15%),BC混合型9例(6%),未发现A、D和E基因型。拉米夫定治疗的86例患者中,17例(19.7%)发生YMDD变异,B型14例,C型2例,BC混合基因型1例,其中6例发生多重变异,包括B型4例,C型2例;HBeAg/HBeAb血清转换率B型41例(68.3%)高于C型8例(40%)(P<0.05)。另外17例患者,经拉米夫定治疗后,HBVDNA仍阳性,亦未发现YMDD变异株。结论湖北地区HBV存在B、C和BC混合基因型,B型为本地区优势基因型,B型在拉米夫定治疗中更易发生YMDD变异;未变异者,血清HBeAg/HBeAb转换率高。

Effect of Lamivudine on Genotypes of Hepatitis B Virus in Hubei Province

Objective: To investigate the effect of lamivudine on genotypes of hepatitis B virus and its clinical significance in Hubei Province. Methods: Serum samples from 160 cases with chronic HBV infection were collected and tested for HBV genotypes by type-specific primers. The YMDD gene order, G1896A, A1814C, A1792T and G1764A were analyzed by gene chips technique for 86 cases with chronic hepatitis B 18 months after treatment with lamivudine. Results: Of 160 patients, 127 cases (79%) were genotype B, 24 cases (15%) were genotype C, 9 cases (6%) were BC mixed genotype, no genotype A, D and E were found. Among 86 patients with 18 months lamivudine treatment, 17 cases ( 19.7% ) were found to have YMDD mutations, including 14 cases with genotype B, 2 cases with genotype C and one case with genotype BC. Six cases developed multi-mutation, including 4 cases of genotype B and 2 cases of genotype C. The conversion rate of serum HBeAg in patients with genotype B (41case) virus infection was significantly higher than those with genotype C (8 cases) infection ( 68.3% vs 40%, P< 0.05 ). The HBV DNA of the other 17 cases were positive without YMDD mutation after treatment with lamivudine. Conclusions: Genotype B, genotype C and BC combination existed in Hubei Province, genotype B is the major genotype in this area and is easliy develop YMDD mutations during lamivudine treatment. The conversion rate of serum HBeAg in patients with genotype B virus infection is higher in those without YMDD mutations during lamivudine treatment.