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接受乙型肝炎核心抗原阳性肝移植物的受者应用乙型肝炎免疫球蛋白时发生乙型肝炎病毒变异的逃逸。

Escape hepatitis B virus mutations in recipients of antibody to hepatitis B core antigen-positive liver grafts receiving hepatitis B immunoglobulins.

机构信息

Centre Hepato-Biliaire, AP-HP Hopital Paul Brousse, Villejuif, France.

出版信息

Liver Transpl. 2010 Jul;16(7):885-94. doi: 10.1002/lt.22084.

DOI:10.1002/lt.22084
PMID:20583085
Abstract

A variety of prophylactic strategies are used to prevent the risk of hepatitis B virus (HBV) transmission from antibody to hepatitis B core antigen (anti-HBc)-positive donors. The mechanisms underlying the failure of HBV immunoglobulin monoprophylaxis have been poorly evaluated. Seventy-seven anti-HBc-positive grafts were used in 21 hepatitis B surface antigen (HBsAg)-positive recipients and 56 HBsAg-negative recipients. HBsAg-positive recipients received prophylaxis comprising hepatitis B immunoglobulins (HBIG) and antiviral agents, 45 HBsAg-negative recipients received a modified HBIG regimen, and 11 HBsAg-negative recipients received no prophylaxis. Both donors and recipients were screened for HBsAg, antibody to HBsAg (anti-HBs) and anti-HBc in their sera and for HBV DNA in both their sera and liver. S gene mutations were investigated after HBV reinfection. HBV infection occurred in 15 HBsAg-negative recipients (19.4%) at a median interval of 16 months (range = 6-67 months) post-transplant and in none of the HBsAg-positive recipients. HBV infections were observed in 31.6% of HBV-naive recipients and 7.7% of HBV-immune recipients receiving HBIG prophylaxis versus 100% of HBV-naive recipients (P = 0.0068) and 33% of HBV-immune recipients (P = 0.08) with no such prophylaxis. S gene mutations were identified in 9 recipients. In conclusion, priority should be given to using anti-HBc positive grafts for HBsAg-positive or HBV-immune recipients. Our study has confirmed the high risk of HBV transmission to naive recipients. HBIG monoprophylaxis was associated with a significant risk of de novo HBV infection and HBV escape mutations. In these patients, we therefore recommend prophylaxis with lamivudine or new nucleos(t)ides analogues. The potential benefits of HBIG prophylaxis combined with antiviral drugs require further evaluations. Long-term prophylaxis is needed because of the long interval of de novo HBV infection post-transplant in some patients.

摘要

预防乙型肝炎病毒 (HBV) 从抗乙型肝炎核心抗原 (抗-HBc) 阳性供体传播的策略多种多样。HBV 免疫球蛋白单预防失败的机制尚未得到很好的评估。21 例乙型肝炎表面抗原 (HBsAg) 阳性受者和 56 例 HBsAg 阴性受者使用了 77 例抗-HBc 阳性移植物。HBsAg 阳性受者接受包括乙型肝炎免疫球蛋白 (HBIG) 和抗病毒药物的预防,45 例 HBsAg 阴性受者接受改良 HBIG 方案,11 例 HBsAg 阴性受者未接受预防。供者和受者均接受血清 HBsAg、抗 HBs 和抗-HBc 筛查,并接受血清和肝组织 HBV DNA 筛查。HBV 再感染后研究 S 基因突变。HBV 感染发生在 15 例 HBsAg 阴性受者中(19.4%),中位时间为移植后 16 个月(范围=6-67 个月),无一例 HBsAg 阳性受者发生。在未接受 HBIG 预防的 HBV 无感染受者中,HBV 感染发生率为 31.6%,在接受 HBIG 预防的 HBV 免疫受者中为 7.7%,而在未接受 HBIG 预防的 HBV 无感染受者中为 100%(P=0.0068),在接受 HBIG 预防的 HBV 免疫受者中为 33%(P=0.08)。9 例受者中鉴定出 S 基因突变。总之,应优先为 HBsAg 阳性或 HBV 免疫受者使用抗-HBc 阳性移植物。本研究证实了 HBV 对无感染受者传播的高风险。HBIG 单预防与新的 HBV 感染和 HBV 逃逸突变显著相关。因此,我们建议在这些患者中使用拉米夫定或新型核苷(酸)类似物进行预防。HBIG 预防联合抗病毒药物的潜在益处需要进一步评估。由于一些患者移植后新的 HBV 感染间隔时间较长,因此需要长期预防。

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