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Preliminary Clinical Study of Anti-HBV-DC Combine Lamivudine and Thymosin-a1 Treating the HBeAg Positive Chronic Hepatitis B Patients
发布时间: 2012-08-04    人气指数:2222

 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-a12010年北京第20届亚肝会吴邦富发言2010年北京第20届亚肝会吴邦富发言 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 have2 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(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。ALT2倍正常值者11例,ALT2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PBMCGM-CSFIL-4诱导扩增DC,第6天给予30μgHBsAg致敏DC,第7天收获抗HBV-DC,皮下和静脉各注射1/2。每21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0412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 0412周的HBsAg分别为(454.06±353.59)ng/ml(155.14±129.50)ng/ml(t=4.28P<0.001)(100.86±91.53)ng/ml(t=4.60P<0.001)HBeAg(26.46±38.16)PEIU/ml(5.57±8.68) PEIU/ml(t=2.74P=0.013)(4.47±7.96)PEIU/ml(t=2.90P=0.009)HBeAb(0.13±0.33)PEIU/ml(0.54±1.17)PEIU/ml(t=1.96P=0.064)(0.60±0.94)PEIU/ml(t=3.06P=0.006)HBV-DNA(76.28±129.35)×105copy/ml(0.61±0.99)×105copy/ml(t=2.62P=0.017)(0.50±1.20)×105copy/ml(t=2.63P=0.017)ALT(101.85±67.89)U/L(72.90±47.31)U/L(t=1.77P=0.093)(51.50±28.83)U/L(t=3.25P=0.004)全部患者治疗后412HBsAgHBeAgHBV-DNA明显下降。4周时5ALT降至正常,3例较前升高,但12周时下降,12周时另5ALT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112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11HBV-DNA转阴,HBV-DNA转阴率55%(11/20)12周时另2HBV-DNA转阴, HBV-DNA总转阴率65%(13/20)有效率100%(20/20)

    结论 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HBsAgHBeAgHBV-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。