HBV活跃复制肝移植受体在拉米夫定预防下HBV标志物动态变化的研究

Investigation on the dynamic alterations of HBV markers in HBV active replication recipient after liver transplantation

目的 了解乙型肝炎病毒 (HBV )活跃复制的受体在拉米夫定预防下肝移植术后HBV标志物的动态变化 ,为预防复发寻找切入点。方法 用酶联放免法、HBVDNA荧光定量法、免疫组化LSAB法及肝穿组织HBVDNA原位杂交法定期检测 15例受体血清及肝穿组织 ,观察肝移植术后HBV标志物在血清及组织中的动态变化。结果 术前口服拉米夫定平均 2周能使 80 %以上的病人血清HBVDNA转阴 ;术后继续口服 ,部分血清乙型肝炎病毒抗体 (抗 HBs、抗 HBc及抗 HBe)可在术后 1～ 2周出现 ,至半年时可逐渐消失 ;血清中HBVDNA荧光定量可一直维持阴转的状态 ;肝穿组织中HBsAg、HBcAg及HBVDNA原位杂交则可长期维持阴性 ;7例HBV活跃复制受体 ,其HBV血清标志物及肝穿组织中HBV标志物在 12周至 44周之间完全消失。若血清中出现表面抗原、HBVDNA荧光定量阳性、肝穿组织免疫组化及HBVDNA原位杂交阳性 ,则可诊断新肝再感染 ;若合并有转氨酶及血清胆红素升高 ,应诊断为新肝乙型肝炎。结论 拉米夫定能有效地预防HBV活跃复制的受体肝移植术后新肝HBV再感染直至清除受体体内残存的HBV。

Objective To investigate the dynamic alternations of HBV markers in HBV active replication recipient after liver transplantation under lamivudine prophylaxis. Methods The serial liver biopsy specimens and sera of 15 recipients have been collected and detected with Enzyme linked radioimmunoassay for HBsAg, HBeAg, Anti HBs, Anti HBc and Anti HBe; fluorecent quantitative assay for quantitation of HBV DNA in serology; immunohistochemistry stain of HBsAg, HBcAg and HBV DNA hybridization in situ for detection of HBV markers in liver biopsy specimens. Results That 100mg lamivudine per oral daily for 2 weeks prior to transplantation enable 12 (80%) of 15 active viral replication recipient (HBV DNA positive) to convert to HBV DNA negative. Anti HBs, Anti HBc and Anti HBe in serum appear in 1～2 weeks after LTX, and subside gradually within 6 months; HBV DNA fluorecent quantitative assay shows negative serum conversion postoperatively. Immunohistochemistry stain of HBsAg, HBcAg and HBV DNA hybridization in situ in liver biopsy specimens shows negative result. 7 of 15 active viral replication recipients lose their HBV markers thoroughly in both serology and HBV DNA hybridization in situ of liver biopsy specimens between 12～44 weeks after liver transplantation. If HBsAg appears, or HBV DNA become positive serologically or immunohistochemistryly in the liver tissue, the de novo liver graft infection can be diagnosed; furthermore if associated with elevation of serum ALT and bilirubin, recurrence of the HBV can be established. Conclusion The graft infecton of HBV active viral replication recipient can be prevented by lamivudine prophylaxis, and furthermore the extinction of HBV is not impossible if proper measures are taken.