背景:肝移植后HBV(乙型肝炎病毒)的再激活可能与共价闭合环状(ccc)DNA的持久性有关。我们调查了选定的HBV移植患者HBV预防戒断的安全性。
方法:30例患者在64-195个月前移植(23例男性,中位年龄56岁),HBsAg阳性,HBeAg,移植时HBV-DNA阴性(43%HCV/HDV共感染),与检测不到肝内总和ccc-DNA入组。所有患者均接受HBIg停药,并继续拉米夫定,每月进行HBsAg和HBV-DNA监测以及序贯肝活检。那些在停止HBIg后24周确认肝内总和ccc-DNA无法检测的人也接受了拉米夫定戒断,并在没有预防的情况下进行了随访。
结果:25例患者在预防性停药后没有表现出HBV复发的迹象(中位随访28.7个月,范围22-42)。五名患者成为HBsAg阳性:HBIg停药后早期,其他四个后HBIg和拉米夫定退出。这些患者均未出现临床相关事件。在第一个病人中,HBIg恢复并迅速HBsAg阴性。在其他四个中,一个仍然是HBsAg阳性,可检测到HBV-DNA和轻度丙氨酸转氨酶升高,并成功地与替诺福韦治疗。剩下的三个,HBsAg阳性是短暂的,然后是抗HBs转化;因此不需要抗病毒治疗。
结论:患者在移植时检测不到HBV病毒血症,没有证据表明肝内总和ccc-DNA可以安全地进行谨慎的断奶预防,显示2年随访后HBV复发率低。肝内ccc-DNA的不可检测性可能有助于识别复发风险低的患者;但需要更长的随访研究。
BACKGROUND: HBV (hepatitis B virus) reactivation after liver transplantation may be related to persistence of covalently closed circular (ccc) DNA. We investigated the safety of HBV prophylaxis withdrawal in selected HBV transplanted patients.
METHODS: Thirty patients transplanted 64-195 months earlier (23 males, median age 56 years), HBsAg-positive, HBeAg, and HBV-DNA-negative at transplant (43% HCV/HDV coinfected), with undetectable intrahepatic total and ccc-DNA were enrolled. All patients underwent HBIg withdrawal and continued lamivudine with monthly HBsAg and HBV-DNA monitoring and sequential liver biopsies. Those with confirmed intrahepatic total and ccc-DNA undetect-ability 24 weeks after stopping HBIg also underwent lamivudine withdrawal and were followed up without prophylaxis.
RESULTS: Twenty-five patients did not exhibit signs of HBV recurrence after prophylaxis withdrawal (median follow-up 28.7 months, range 22-42). Five patients became HBsAg-positive: one early after HBIg withdrawal, the other four after HBIg and lamivudine withdrawal. None of these patients experienced clinically relevant events. In the first patient, HBIg were reinstituted with prompt HBsAg negativization. Of the other four, one remained HBsAg-positive with detectable HBV-DNA and mild alanine transaminase elevation and was successfully treated with tenofovir. In the remaining three, HBsAg positivity was transient and followed by anti-HBs se-roconversion; thus no antiviral treatment was needed.
CONCLUSIONS: Patients with undetectable HBV viremia at transplant and no evidence of intrahepatic total and ccc-DNA may safely undergo cautious weaning of prophylaxis, showing the low rate of HBV recurrence after a 2-year follow-up. Undetectability of intrahepatic ccc-DNA may help to identify patients at low risk of recurrence; yet studies with longer follow-up are needed.