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肝移植治疗乙型肝炎后,无需使用乙型肝炎免疫球蛋白的口服核苷(酸)类似物。

Oral nucleoside/nucleotide analogs without hepatitis B immune globulin after liver transplantation for hepatitis B.

机构信息

Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.

出版信息

Am J Gastroenterol. 2013 Jun;108(6):942-8. doi: 10.1038/ajg.2013.111. Epub 2013 Apr 30.

Abstract

OBJECTIVES

The long-term outcomes of oral antiviral therapy without hepatitis B immune globulin (HBIG) in prevention of reinfection with hepatitis B after liver transplantation are not known. We aimed to determine the long-term outcomes from a large population of chronic hepatitis B (CHB) liver transplant recipients using oral antiviral therapy alone.

METHODS

A total of 362 consecutive CHB patients transplanted from January 2003 to May 2011 were included. None of the patients received HBIG. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow-up.

RESULTS

Of the 362 patients, 176 (49%), 142 (39%), and 44 (12%) were on lamivudine (LAM), entecavir (ETV), and combination therapy (predominantly LAM+adefovir), respectively, at the time of transplant. The median follow-up length was 53 months. The rate of hepatitis B surface antigen seronegativity and hepatitis B virus (HBV) DNA suppression to undetectable levels at 8 years was 88 and 98%, respectively. The virological relapse rates (>1 log increase IU/ml) at 1, 3, 5, and 8 years was 5, 10, 13 and 16%, respectively. The virological relapse rate at 3 years for LAM, ETV, and combination group was 17, 0, and 7%, respectively (P<0.001). Forty-two patients had virological relapse, of which 36 had YMDD mutation (31 in the LAM group and 5 in the combination group). The overall 8-year survival was 83%, with no difference between the three treatment groups (P=0.94). No mortality from HBV recurrence occurred in the 362 patients.

CONCLUSIONS

Oral nucleoside/nucleotide analogs without HBIG are effective in preventing graft loss secondary to hepatitis B recurrence after liver transplantation. However, new agents with a high barrier to resistance should be used to minimize drug resistance and to prevent virological rebound.

摘要

目的

在预防乙型肝炎(HBV)肝移植后再感染方面,不使用乙型肝炎免疫球蛋白(HBIG)的口服抗病毒治疗的长期结果尚不清楚。我们旨在通过单独使用口服抗病毒治疗来确定来自大量慢性乙型肝炎(CHB)肝移植受者的长期结果。

方法

共纳入 2003 年 1 月至 2011 年 5 月期间接受 CHB 治疗的 362 例连续患者。所有患者均未接受 HBIG。在随访期间,定期进行病毒学检测、病毒载量和肝功能检查。

结果

362 例患者中,176 例(49%)、142 例(39%)和 44 例(12%)分别在移植时使用拉米夫定(LAM)、恩替卡韦(ETV)和联合治疗(主要为 LAM+阿德福韦)。中位随访时间为 53 个月。8 年后乙型肝炎表面抗原阴性和 HBV DNA 抑制至不可检测水平的比例分别为 88%和 98%。1、3、5 和 8 年后病毒学复发率(>1 log IU/ml)分别为 5%、10%、13%和 16%。LAM、ETV 和联合组 3 年的病毒学复发率分别为 17%、0%和 7%(P<0.001)。42 例患者发生病毒学复发,其中 36 例存在 YMDD 突变(LAM 组 31 例,联合组 5 例)。8 年总体生存率为 83%,三组间无差异(P=0.94)。362 例患者均未因 HBV 复发而死亡。

结论

不使用 HBIG 的口服核苷(酸)类似物在预防乙型肝炎肝移植后因乙型肝炎复发导致移植物丢失方面是有效的。然而,应该使用耐药屏障高的新型药物,以最大限度地减少耐药性并防止病毒学反弹。

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