核苷类似物单药口服预防肝移植术后乙型病毒性肝炎复发的研究
Research on the oral nucleoside analogues monotherapy in the prevention of hepatitis B recurrence of patients after liver transplantation
-
摘要:目的 探讨核苷类似物单药口服预防肝移植术后乙型病毒性肝炎(乙肝)复发的有效性和安全性。方法 回顾性分析1999年10月至2014年4月在广东佛山市第一人民医院行肝移植的32例乙肝相关性疾病患者的临床资料。根据供体来源分为两个阶段。第一阶段为1999年10月至2007年9月的6例无心跳供体肝移植,供肝的乙型肝炎病毒(HBV)血清标志物均为(-),受体术前血清乙型肝炎表面抗原(HBsAg)、乙型肝炎核心抗体(抗-HBc)均为(+),其中2例合并乙型肝炎e抗原(HBeAg)(+),1例合并乙型肝炎e抗体(抗-HBe)(+),5例受体术前血清HBV 脱氧核糖核酸(DNA)>1 000 copies/ml,1例HBV DNA<1 000 copies/ml。给予拉米夫定(100 mg/d)单药口服预防肝移植术后乙肝复发。第二阶段为2011年11月至2014年4月的26例心脏死亡器官捐献供体肝移植(其中1例为肝肾联合移植);供肝血清HBsAg(+)6例、(-)20例,乙型肝炎表面抗体(抗-HBs)(+)15例,HBeAg(+)2例,抗-HBc(+)14例,抗-HBe(+)5例;11例受体术前血清HBV DNA>500 copies/ml,15例HBV DNA<500 copies/ml;25例给予恩替卡韦0.5 mg/d、1例给予替比夫定600 mg/d单药口服预防乙肝复发。结果 第一阶段肝移植受体中位随访时间为104个月,全部受体术后血清HBsAg和HBV DNA均转阴,至今未见乙肝复发。第二阶段肝移植受体中位随访时间为50周,20例接受HBsAg(-)供肝,其中1例于术后39周出现一过性HBsAg(+),随后又转阴;另1例肝肾联合移植受体在移植术后28周发生乙肝复发,但血清HBV DNA(-);其中15例采用抗-HBc(+)供体肝移植术后均未见乙肝复发。6例采用HBsAg(+)供体的肝移植受体术后HBsAg均未转阴。所有随访受体均存活,术后均未见HBV DNA复制,亦未发现核苷类似物相关不良反应。结论 核苷类似物单药口服预防肝移植术后乙肝的复发是有效和安全的。Abstract:Objective To explore the efficacy and safety of the oral nucleoside analogues monotherapy in the prevention of hepatitis B recurrence of patients after liver transplantation (LT).Methods Clinical data of 32 patients with hepatitis B-related disease undergoing LT in the First People's Hospital of Foshan in Guangdong Province from October 1999 to April 2014 were retrospectively analyzed. The patients were divided into two phase groups according to the source of donors. Phase 1 was from October 1999 to September 2007 when 6 patients receiving LT of non-heart-beating donors. The serum hepatitis B virus(HBV) markers of 6 donor livers were all negative. The serum hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) of the recipients before operation were all positive, including 2 cases combined with Hepatitis B e antigen (HBeAg) positive, 1 case combined with hepatitis B virus e antibody (anti-HBe) positive. The serum HBV deoxyribonucleic acid (DNA) of 5 recipients before LT were over 1 000 copies/ml and 1 case were below 1 000 copies/ml. All the patients in phase 1 group were given lamivudine (100 mg/d) monotherapy orally for the prevention of hepatitis B recurrence after LT. Phase 2 was from November 2011 to April 2014 when 26 patients receiving LT of donation after cardiac death including 1 case of combined liver-kidney transplantation. Six of the donor livers were with serum HBsAg positive and 20 cases negative. Fifteen cases were with hepatitis B surface antibody (anti-HBs) positive and 2 cases with HBeAg positive, 14 cases with anti-HBc positive and 5 with anti-HBe positive. The serum HBV DNA of 11 recipients before LT were over 500 copies/ml and 15 cases below 500 copies/ml. Twenty-five cases were given entecarvir 0.5 mg/d and 1 case telbivudine 600 mg/d monotherapy orally for the prevention of hepatitis B recurrence.Results The median follow-up time of the recipients in group phase 1 was 104 months. The serum HBsAg and HBV DNA were both negative in all recipients and no hepatitis B recurrence was observed till now. The median follow-up time of the recipients in group phase 2 was 50 weeks. Twenty cases received donor livers of negative HBsAg, in which 1 case had transient positive HBsAg 39 weeks after LT and became negative later. The patient receiving combined liver-kidney transplantation suffered hepatitis B recurrence 28 weeks after LT but HBV DNA was observed negative. No hepatitis B recurrence was observed in the 15 cases receiving donor livers of positive anti-HBc. Six cases receiving donor livers of positive HBsAg failed to become negative HBsAg after LT. All the follow-up recipients survived. No HBV DNA replication was observed in the recipients after LT. No adverse reaction of related nucleoside analogues was observed.Conclusion It is effective and safe to use nucleoside analogues monotherapy for the prevention of hepatitis B recurrence in patients after LT.
下载: