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肝移植后乙型肝炎复发的抗病毒预防:当前概念。

Antiviral prophylaxis against hepatitis B recurrence after liver transplantation: Current concepts.

机构信息

Academic Department of Gastroenterology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece.

First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece.

出版信息

Liver Int. 2021 Jul;41(7):1448-1461. doi: 10.1111/liv.14860. Epub 2021 Mar 12.

Abstract

The advance in treatment against hepatitis B virus (HBV) infection with the development of nucleos(t)ide analogues (NAs) with high genetic barrier to resistance, including entecavir and tenofovir, has improved clinical outcomes of patients transplanted for HBV infection, by preventing HBV recurrence after liver transplantation (LT) effectively. Currently, after LT, the combination of hepatitis B immunoglobulin (HBIG) and a high-barrier NA is considered as the standard of care for prophylaxis against HBV recurrence. However, because of the high cost of intravenous high-dose HBIG, other routes of HBIG administration, such as intramuscular or subcutaneous, have come to the foreground. In addition, several transplant centres tend to use a NA as monoprophylaxis, following a short post-LT period of HBIG and NA combination. Lately, studies using HBIG-free prophylactic regimens with entecavir or tenofovir have shown promising outcomes in preventing HBV recurrence, mostly regarding patients with undetectable HBV DNA at the time of LT. Although vaccination against HBV has been an attractive prophylactic approach, its efficacy has been controversial. Moreover, further studies are needed regarding long-term outcomes of complete withdrawal anti-HBV prophylaxis. For patients transplanted for HBV/HDV co-infection, combined regimen should be administered for a longer period post-LT. Finally, the use of grafts from hepatitis B core antibody-positive donors is safe for HBV-negative recipients, with the administration of lifelong antiviral prophylaxis.

摘要

随着具有高耐药遗传屏障的核苷(酸)类似物(NAs)的发展,乙型肝炎病毒(HBV)感染的治疗取得了进展,包括恩替卡韦和替诺福韦,这有效预防了肝移植(LT)后 HBV 的复发,从而改善了 HBV 感染患者的临床转归。目前,LT 后,联合使用乙型肝炎免疫球蛋白(HBIG)和高屏障 NA 被认为是预防 HBV 复发的标准治疗方法。然而,由于静脉内高剂量 HBIG 的成本较高,HBIG 的其他给药途径,如肌肉内或皮下,已成为研究热点。此外,一些移植中心倾向于在 LT 后使用 NA 进行单药预防,在 HBIG 和 NA 联合治疗的短期阶段后。最近,使用恩替卡韦或替诺福韦的无 HBIG 预防性方案的研究表明,在预防 HBV 复发方面取得了有希望的结果,主要针对 LT 时 HBV DNA 不可检测的患者。虽然乙型肝炎疫苗接种是一种有吸引力的预防方法,但它的疗效存在争议。此外,还需要进一步研究完全停止抗 HBV 预防的长期结果。对于乙型肝炎/丁型肝炎病毒(HDV)合并感染的患者,联合方案应在 LT 后更长时间内使用。最后,对于 HBV 阴性受者,使用乙型肝炎核心抗体阳性供体的移植物是安全的,需要终身抗病毒预防。

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