Bienzle Ulrich, Günther Matthias, Neuhaus Ruth, Vandepapeliere Pierre, Vollmar Jens, Lun Andreas, Neuhaus Peter
Institute of Tropical Medicine, Charité, Humboldt University, Spandauer Damm 130, 14050 Berlin, Germany.
Hepatology. 2003 Oct;38(4):811-9. doi: 10.1053/jhep.2003.50396.
Patients who undergo transplantation for hepatitis B virus (HBV)-related diseases are treated indefinitely with hepatitis B hyperimmunoglobulin (HBIG) to prevent endogenous HBV reinfection of the graft. Active immunization with standard hepatitis B vaccines in these patients has recently been reported with conflicting results. Two groups of 10 liver transplant recipients on continuous HBIG substitution who were hepatitis B surface antigen (HBsAg) positive and HBV DNA negative before transplantation were immunized in a phase I study with different concentrations of hepatitis B s antigen formulated with the new adjuvants 3-deacylated monophosphoryl lipid A (MPL) and Quillaja saponaria (QS21) (group I/vaccine A: 20 microg HBsAg, 50 microg MPL, 50 microg QS21; group II/vaccine B: 100 microg HBsAg, 100 microg MPL, 100 microg QS21). Participants remained on HBIG prophylaxis and were vaccinated at weeks 0, 2, 4, 16, and 18. They received 3 additional doses of vaccine B at bimonthly intervals if they did not reach an antibody titer against hepatitis B surface antigen (anti-HBs) greater than 500 IU/L. Sixteen (8 in each group) of 20 patients (80%) responded (group I: median, 7,293 IU/L; range, 721-45,811 IU/L anti-HBs; group II: median, 44,549 IU/L; range, 900-83,121 IU/L anti-HBs) and discontinued HBIG. They were followed up for a median of 13.5 months (range, 6-22 months). The vaccine was well tolerated. In conclusion, most patients immunized with the new vaccine can stop HBIG immunoprophylaxis for a substantial, yet to be determined period of time.
接受乙型肝炎病毒（HBV）相关疾病移植的患者需长期接受乙型肝炎高效价免疫球蛋白（HBIG）治疗，以预防移植物的内源性HBV再感染。近期有报道称，对这些患者使用标准乙型肝炎疫苗进行主动免疫，结果相互矛盾。在一项I期研究中，两组接受持续HBIG替代治疗的肝移植受者，在移植前乙型肝炎表面抗原（HBsAg）呈阳性且HBV DNA呈阴性，分别用含有新型佐剂3-脱酰基单磷酰脂质A（MPL）和皂树（QS21）配制的不同浓度乙型肝炎表面抗原进行免疫（I组/疫苗A：20μg HBsAg、50μg MPL、50μg QS21；II组/疫苗B：100μg HBsAg、100μg MPL、100μg QS21）。参与者继续接受HBIG预防，并在第0、2、4、16和18周接种疫苗。如果他们的乙型肝炎表面抗原抗体（抗-HBs）滴度未超过500 IU/L，将每两个月额外接种3剂疫苗B。20名患者中有16名（每组8名，80%）产生了应答（I组：抗-HBs中位数为7293 IU/L；范围为721 - 45811 IU/L；II组：抗-HBs中位数为44549 IU/L；范围为900 - 83121 IU/L），并停止使用HBIG。他们的中位随访时间为13.5个月（范围为6 - 22个月）。该疫苗耐受性良好。总之，大多数接种新型疫苗的患者在一段尚未确定的相当长的时间内可以停止HBIG免疫预防。
