| Preliminary Clinical Study of Anti-HBV-DC Combine Lamivudine and Thymosin-a1 Treating the HBeAg Positive Chronic Hepatitis B Patients |
发布时间： 2010-04-02 人气指数：3808 |
The 20th Conference of the Asian Pacific Association for the Study of the Liver
Oral Presentations(FP021)
Hepatology International.2010, 4(1):18-19 Bang-Fu Wu1,2, Jiang-Ying Yang2, Fang-Qin Li1, Fu-Xin Lin1,Wen-Bao Zhu1,Yun Zhou2, Yan-Ping Fu1, Jun Yang2, Xue-Song Li1, Wei Zheng1, Wei Chen1,Hui-Hua Zhou1, Chun-Qiong Hou1 1Gastroenterology and Hepatology Center, Tongji Medical College Affiliated Dongguan Hospital, Huazhong University of Science and Technology, Liaobu Southwest Road, No.171-175, Dongguan, China, 2Guangzhou Pubang Biological Immune Technology Research Center, Room 904, D District,Guangzhou International Business Incubator, Guangzhou Science City,Luogang District, Guangzhou, China
Background: To observe the clinical treatment effects of the HBsAg pulsed autologous dendritic cells (anti-HBV-DC) derived from peripheral blood mononuclear cells (PBMC) combine lamivudine and Thymosin-a1 for the HBeAg positive chronic hepatitis B (CHB) patients.
Methods: 20 patients with HBeAg positive CHB included in the study. 11 patients have ≤2 times the normal value ALT. 9 patients have＞2 times the normal value ALT. Taking peripheral venous blood 50 ml, by density gradient centrifugation and adhesion method to obtain PBMC, GM-CSF and IL-4 induced expansion of DC. At 6 days, a 30 μg HBsAg was give to pulse the DCs. At seventh days, the anti-HBV-DCs were harvested and were injected into body by subcutaneous and intravenous. Every 2 weeks one time, a total of six times. 100 mg Lamivudine every day, and 1.6 mg thymosin-a1 every one week 2 times. The HBVM (TRFIA), HBVDNA and ALT were respectively detected at 0, 4, 12 weeks.
Result: All patient’s the serum HBsAg, HBeAg and HBVDNA were significantly decreased at 4, 12 weeks. Ten patient’s ALT decreased to normal. The HBeAg/HBeAb seroconversion occurred in 4 patients at 4 weeks. The conversion rate was 20% (4/20). The HBeAg/HBeAb seroconversion occurred in other five patients at 12 weeks. The total HBeAg/HBeAb seroconversion rate was 45% (9/20). The serum HBVDNA negative conversion occurred in 11 patients at 4 weeks, the conversion rate was 55% (11/20). The serum HBVDNA negative conversion occurred in other two patients at 12 weeks. The total serum HBVDNA negative conversion rate was 65% (13/20). The total effective rate was 100% (20/20).
Conclusion: The anti-HBV-DC combine lamivudine and Thymosin-a1 can effectively inhibit HBVDNA replication, decrease rapidly the serum HBsAg, HBeAg and HBVDNA levels, promote to the HBeAb production, and enhance the HBeAg/HBeAb seroconversion rate, which were a safe and efficient treatment method for the HBeAg positive CHB patients.
抗HBV-DC联合拉米夫定和胸腺肽a1治疗e抗原阳性慢性乙型肝炎的初步临床研究 第20届亚太肝脏研究会年会(北京) 口头发言(FP021) Hepatology International.2010, 4(1):18-19 华中科技大学同济医学院附属东莞医院消化肝病中心 吴邦富 李芳琴 凌佛鑫 朱文宝 付彦平 李雪松 侯春琼 郑硕 陈伟 周慧华 广州普邦生物免疫技术研究院 杨江英 周赟 杨军 目的 观察HBsAg致敏自体外周血单个核细胞(PBMC)来源的树突状细胞(抗HBV-DC)联合拉米夫定和胸腺肽a1治疗HBeAg阳性慢性乙型肝炎(CHB)的临床效果。 方法 HBeAg阳性CHB患者20人接受临床研究。ALT≤2倍正常值者11例，ALT＞2倍者9例。取肝素抗凝外周静脉血50ml，以密度梯度离心及贴壁法获得PBMC，GM-CSF和IL-4诱导扩增DC，第6天给予30μg的HBsAg致敏DC，第7天收获抗HBV-DC，皮下和静脉各注射1/2。每2周1次，共6次。口服拉米夫定每次100mg，每天1次。皮下注射1.6mg胸腺肽a1，每周2次。分别于0、4、12周检测HBVM定量(时间分辨荧光免疫分析技术，TRFIA)、HBV-DNA定量及肝功能。 结果 0、4、12周的HBsAg分别为(454.06±353.59) ng/ml、(155.14±129.50) ng/ml(t=4.28，P<0.001) 和(100.86±91.53) ng/ml (t=4.60，P<0.001)； HBeAg(26.46±38.16) PEIU/ml、(5.57±8.68) PEIU/ml(t=2.74，P=0.013)和(4.47±7.96)PEIU/ml (t=2.90，P=0.009)； HBeAb(0.13±0.33)PEIU/ml、(0.54±1.17)PEIU/ml (t=1.96，P=0.064) 和(0.60±0.94) PEIU/ml (t=3.06，P=0.006)；HBV-DNA (76.28±129.35)×105 copy/ml、(0.61±0.99)×105copy/ml (t=2.62，P=0.017) 和(0.50±1.20)×105 copy/ml(t=2.63，P=0.017)； ALT(101.85±67.89)U/L、(72.90±47.31)U/L(t=1.77，P=0.093)和(51.50±28.83)U/L(t=3.25，P=0.004)。全部患者治疗后4、12周的HBsAg、HBeAg和HBV-DNA均明显下降。4周时5例ALT降至正常，3例较前升高，但12周时下降，12周时另5例ALT降至正常。4周时6例出现HBeAg/HBeAb血清学转换，转换率30%(6/20), 其中1例12周时转回HBeAg阳性和HBeAb阴性；12周时另4例出现HBeAg/HBeAb血清学转换，总转换率45%(9/20)。4周时11例HBV-DNA转阴，HBV-DNA转阴率55%(11/20)；12周时另2例HBV-DNA转阴， HBV-DNA总转阴率65%(13/20)。总有效率100%(20/20)。 结论 抗HBV-DC皮下和静脉注射联合拉米夫定和胸腺肽a1治疗，可有效地抑制HBeAg阳性CHB患者的HBV-DNA复制，快速降低血中HBsAg、HBeAg和HBV-DNA，促进HBeAb的产生，提高HBeAg/HBeAb的血清学转换率，是一种安全、高效的治疗HBeAg阳性CHB患者的方法。 |
