拉米夫定治疗失代偿乙型肝炎肝硬化的疗效与HBV基因型及细胞毒性T淋巴细胞的关系

Relationship between effect of Lamivudine in the treatment of cirrhotic patients with uncompensated hepatitis B with HBV genotypes and cytotoxic T lymphocyte

目的探讨拉米夫定治疗失代偿乙型肝炎肝硬化的疗效与乙型肝炎病毒（HBV）基因型及HBV特异性细胞毒性T淋巴细胞（CTL）的关系。方法80例失代偿乙型肝炎肝硬化患者（B基因型和C基因型各40例），HBVDNA阳性、HBeAg阳性、人白细胞抗原（HLA）-A2阳性，用拉米夫定100mg／d治疗，观察1年后的疗效及其与HBV基因型、HBV特异性CTL的关系。结果HBVDNA转阴：B基因型感染者40例（100％），C基因型感染者治疗至9、10个月时各有1例发生YMDD变异加阿德福韦酯治疗，其余38例中HBVDNA转阴26例（68．42％），HBVDNA转阴率C基因型感染者低于B基因型感染者x^2=14．91，P〈0．01，HBeAg转阴：B基因型感染者18例（45％），多于c基因型感染者（7例，18．42％）x^2=6．32，P〈0．05，外周血HBV特异性CTL水平：治疗前，B基因型感染者（0．33±0．03）％，高于C基因型感染者[（0．11±0．02）％]，t=8．12，P〈0．001，治疗后1年：B基因型感染者0．44±0．04％，高于治疗前，t=4．01，P〈0．001，也高于c基因型感染者治疗后1年[（0．23±0．03）％]，t=5．63，P〈0．01，丙氨酸转氨酶（ALT）恢复正常：B基因型感染者38例（95％），多于C基因型感染者[（28例，73．68）％]x^2=6．79，P〈0．01。结论拉米夫定治疗失代偿乙型肝炎肝硬化患者，C基因型感染者的疗效差于B基因型感染者，其机制可能与C基因型感染者的HBV特异性CTL水平低于B基因型感染者有关。

Objective To explore relationship between effect of Lamivudine in the treatment of cirrhotic patients with uncompensated hepatitis B with hepatitis B virus （HBV）genotypes and HBV specific cytotoxic T lymphoeytes（CTL）. Methods 80 cases of uncompensated cirrhotic hepatitis B（40 cases with genotype B and 40 with genotype C）, HBV DNA positive, HBeAg positive and human leukocyte antigen （HLA）-A2 positive,were treated with Lamivudine 100rag/d, one year later, its effect and relationship with HBV genotypes and HBV specific CTL were observed. Results HBV DNA turned negative：40 cases with genotype B turned negative （ 100% ）. In the 9^th and 10th month of treatment, there was one case with genotype C had YMDD variation respectively and Adefovir dipivoxil was used for treatment, of the rest 38 cases, HBV DNA of 26 cases（68.42% ）turned negative, HBV DNA negative rate of patients with genotype is lower than that of patients with genotype B,X2 = 14. 91, P 〈 0. 01. HBeAg turned negative： 18 cases with genotype B（45% ）turned negative, more than that of patients with genotype C （7 cases, 18.42% ）,X2 = 6.32,P 〈 0. 05. Peripheral blood HBV specific CTL level： before treatment, it was （0. 33 ±0. 03 ） % of patients with genotype B, higher than that of patients with genotype C [ （ 0. 11 ± 0. 02 ） % ], t = 8.12, P 〈 0. 001. 1 year after treatment： it was （0.44 ±0. 04） % of patients with genotype B, higher than that before treatment,t =4.01 ,P 〈0. 001 ,it was also higher than that of patients with genotype C 1 year after treatment [ （0. 23 ±0.03 ） % ] , t = 5.63, P 〈 0.01, alanine amino-transferase （ALT） returned to normal ： 38 cases with genotype B （95%）returned to normal, more than that of patients with genotype C （28 cases,73.68% ） ,X2 = 6. 79 ,P 〈 0.01. Conclusion Effect of Lamivudinein the treatment of cirrhotic patients with uncompensated hepatitis B is better in patients with genotype B than patients with genotype C,its mechanism may be related to lower level of HBV specific CTL in patients with genotype C than patients with genotype B.