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肝移植患者乙肝病毒感染的管理

Management of HBV Infection in Liver Transplantation Patients.

作者信息

Vierling John M

机构信息

David Geffen School of Medicine at University of California, Los Angeles, CA, USA.

出版信息

Int J Med Sci. 2005;2(1):41-49. doi: 10.7150/ijms.2.41. Epub 2005 Jan 5.

Abstract

In the absence of preventative therapy, reinfection of allografts with hepatitis B virus (HBV) after orthotopic liver transplantation (OLT) resulted in dismal allograft and patient survival. Major advances in the management of HBV-infected recipients of OLT during the past 15 years have steadily reduced the rate of reinfection, resulting in improved outcomes. Initially, long-term use of hepatitis B immune globulin (HBIG) as a source of anti-HBs antibodies was effective in preventing or delaying reinfection. Lamivudine monotherapy made it possible to suppress HBV replication prior to OLT, markedly decreasing the risk of reinfection. Although lamivudine monotherapy used before and after OLT could prevent reinfection, its effectiveness was limited by progressive development of lamivudine-resistant mutant infections. Combination therapy with HBIG and lamivudine after OLT reduced both HBV recurrence and the risk of lamivudine resistance even in patients with active HBV replication. Introduction of adefovir provided a safe, alternative oral antiviral able to treat effectively lamivudine-resistant mutants HBV. Available strategies to prevent reinfection have resulted in OLT outcomes for HBV-infected patients comparable to those for patients transplanted for non-HBV indications. In the future, combination therapies of HBIG and both nucleoside and/or nucleotide agents will undoubtedly be optimized. Development of new drugs to treat HBV will increase opportunities to combine agents to enhance safety, efficacy and prevent emergence of HBV escape mutants. New vaccines and adjuvants may make it possible to generate anti-HBs in immunosuppressed patients, eliminating the need for HBIG.

摘要

在缺乏预防性治疗的情况下,原位肝移植(OLT)后乙肝病毒(HBV)对同种异体移植物的再感染导致移植物和患者的生存率极低。在过去15年中,OLT感染HBV患者的管理取得了重大进展,不断降低了再感染率,从而改善了治疗结果。最初,长期使用乙肝免疫球蛋白(HBIG)作为抗-HBs抗体的来源可有效预防或延迟再感染。拉米夫定单药治疗使得在OLT之前抑制HBV复制成为可能,显著降低了再感染风险。尽管OLT前后使用拉米夫定单药治疗可预防再感染,但其有效性受到拉米夫定耐药突变感染逐渐发展的限制。OLT后联合使用HBIG和拉米夫定即使在有活动性HBV复制的患者中也降低了HBV复发率和拉米夫定耐药风险。阿德福韦的引入提供了一种安全的替代性口服抗病毒药物,能够有效治疗拉米夫定耐药的HBV突变体。现有的预防再感染策略已使HBV感染患者的OLT治疗结果与非HBV适应症患者移植后的治疗结果相当。未来,HBIG与核苷和/或核苷酸药物的联合治疗无疑将得到优化。开发治疗HBV的新药将增加联合用药的机会,以提高安全性、疗效并防止HBV逃逸突变体的出现。新疫苗和佐剂可能使免疫抑制患者产生抗-HBs,从而无需使用HBIG。

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