拉米夫定联合乙型肝炎免疫球蛋白预防肝移植后乙肝病毒复发的系统评价_《中国循证医学杂志》

作者：

江自成 ,  江建宁

广西医科大学第一附属医院感染性疾病科（南宁 530021）;

关键词：

肝移植乙型肝炎病毒复发拉米夫定乙型肝炎高效价免疫球蛋白 Meta分析

DOI：

10.7507/1672-2531.20100527

视频：

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摘要 全文 图表 视频 参考文献 施引文献 补充材料

目的评价拉米夫定（lamivudine，LAM）联合乙型肝炎免疫球蛋白（hepatitis B immunoglobulin，HBIG）预防肝移植后乙肝病毒复发的价值。
方法计算机检索MEDLINE（Ovid）、PubMed、EMbase、CENTRAL（Cochrane Central Register of Controlled Trials）、CBM、CNKI、VIP关于LAM联合HBIG与LAM单用预防肝移植后乙肝病毒复发的随机双盲对照、非随机同期对照及病例对照研究。检索时间截至2008年12月。两名研究者独立按Cochrane系统评价方法选择试验、提取资料，并采用RevMan 5.0.18软件进行Meta分析。
结果共纳入11项研究，均为非随机同期对照试验，共1 421例患者，其中LAM联合HBIG组1 035例，LAM单用组386例。结果显示，LAM联合HBIG治疗组较单用LAM治疗组：① 减少乙肝病毒复发风险达73%［RR=0.27，95%CI（0.20，0.37），P lt;0.000 01］；② 减少乙肝病毒YMDD变异风险达72%［RR=0.28，95%CI（0.15，0.53），P=0.000 01］；③ 减少乙肝病毒复发所致的死亡风险达79%［RR=0.21，95%CI（0.09，0.49），P=0.000 3］；④ 受者和移植物总的生存率两组相似［RR=1.03，95%CI（0.95，1.11），P=0.51；RR=1.04，95%CI（0.97，1.12），P=0.26］。
结论现有研究显示LAM联合HBIG治疗比LAM单用可明显减少肝移植后乙肝病毒复发、发生YMDD变异及乙肝病毒复发所致的死亡风险。LAM联合HBIG是预防肝移植后乙肝病毒复发的有效措施。

引用本文： 江自成,江建宁. 拉米夫定联合乙型肝炎免疫球蛋白预防肝移植后乙肝病毒复发的系统评价. 中国循证医学杂志, 2010, 10(8): 964-971. doi: 10.7507/1672-2531.20100527 复制

1.	Rohit L, Rowley AK, Wesley R, et al. Hepatitis B immunoglobulin and lamivudine improve hepatitis B related outcomes after liver transplantation: meta-analysis. Clinical Gastroenterology and Hepatolog, 2008, 6(6): 696-700.
2.	Alter MJ. Epidemiology of hepatitis B in Europe and worldwide. J Hepatol, 2003, 39(Suppl 1): S64-69.
3.	全国人群乙肝血清流行病学调查结果.卫生部与中国疾病预防控制中心, 2008. http://www.chinacdc.net.cn/n272442/n272530/n3246177 /23316.html.
4.	Seehofer D, Rayes N, Neuhaus P. Prophylaxis and treatment of hepatitis B recurrence after liver transplantation in the antiviral era. Expert Rev Anti Infect Ther, 2003, 1(2): 307-318.
5.	Konig V, Hopf U, Neuhaus P, et al. Long-term follow-up of hepatitis B virus-infected recipients after orthotopic liver transplantation. Transplantation, 1994, 58(5): 553-559.
6.	Samuel D, Muller R, Alexander G, et al. Liver transplantation in European patients with the hepatitis B surface antigen. N Engl J Med, 1993, 329(25): 1842-1847.
7.	Large, muticenter, European retrospective study of more than 300 transplant patients illustrating that the risk of recurrence among patients with hepatitis B decreased with hepatitis B immunoglobulin (HBIG) usage.
8.	Fontana RJ, Lok AS. Combination of HBIG and lamivudineresistant mutations: a formula for trouble? Liver Transpl, 2002, 8: 1082-1084.
9.	Saab S, Kim M, Wright TL, et al. Successful orthotopic liver transplantation for lamivudine-associatied YMDD mutant hepatitis B virus. Gastroenterology, 2000, 119(5): 1382-1384.
10.	Dumortier J, Le Derf Y, Guillem P, et al. Favorable outcome of livertransplantation despite a high hepatitis B virus replication: beyond the limits? Transpl Infect Dis, 2006, 8(3): 182-184.
11.	Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology, 2001, 33(2): 464-470.
12.	吴泰相, 刘关键. 隐蔽分组(分配隐藏)和盲法的概念、实施与报告.中国循证医学杂志, 2007, 7(3): 222-225.
13.	王家良, 主编. 循证医学. 北京: 人民卫生出版社, 2005: 60-72.
14.	Sutton AJ, Abrams KR, Jones DR, et al. Methods for meta-analysis in medical research. Wiley: Chichester, 2000.
15.	Hedges LV. Modeling Publication selection effects in meta-analysis. Stat Sci, 1992, 7(2): 246-265.
16.	Freshwater DA, Dudley T, Cane P, et al. Viral persistence after liver transplantation for hepatitis B virus: a cross-sectional study. Transplantation, 2008, 85(8): 1105-1111.
17.	Neff,GW, O’Brien CB, Nery J, et al. Outcomes in liver transplant recipients with hepatitis B virus: Resistance and recurrence patterns from a large transplant center over the last decade. Liver Transplantation, 2004, 10(11): 1372-1378.
18.	Buti M, Mas A, Prieto M, et al. Adherence to lamivudine after an early withdrawal of hepatitis B immune globulin Plays an important role in the long-term prevention of hepatitis B virus recurrence. Transplantation, 2007, 84(5): 650-654.
19.	陈耀敏, 郑树森, 王伟林, 等. 拉米夫定联合乙型肝炎免疫球蛋白防治肝移植后乙型肝炎复发的疗效研究. 浙江医学, 2008, 30(9): 989-990.
20.	朱建平, 李磊, 张同琳, 等. 拉米夫定及乙型肝炎免疫球蛋白预防肝移植后乙型肝炎复发的疗效观察. 外科理论与实践, 2003, 8(6): 479-481.
21.	Zhu JP, Zhang TL, Li L, et al. Prevention and treatment of hepatitis B recurrence after liver transplantation. Hepatobillary & Pancreatic Diseases International, 2003, 2(4): 500-503.
22.	Oldakowska-Jedynak U, Paczek L, Foroncewicz B, et al. Prevention of hepatitis B recurrence after liver transplantation using lamivudine and hepatitis B immune globulin. Ann Transplant, 2007, 12(3): 28-32.
23.	Anselmo DM, Ghobrial RM, Jung LC, et al. New era of liver transplantation for hepatitis B: a 17-year single-center experience. Ann Surg, 2002, 235(5): 611-620.
24.	焦作义, 严律南, 李波, 等. 拉米夫定联合小剂量乙型肝炎免疫球蛋白预防肝移植术后乙型肝炎复发. 中华肝脏病杂志, 2007, 15(11): 804-808.
25.	史宪杰, 周宁新, 纪文斌, 等. 肝移植术后乙型肝炎病毒再感染的预防. 中华医院感染学杂志, 2007, 17(5): 527-529.
26.	王正昕, 丁国善, 付宏, 等. 173例肝移植术后乙型肝炎病毒再感染防治经验回顾. 中华肝胆外科杂志, 2006, 12(9): 616-618.
27.	夏杰, 杨占宇, 陈佳, 等. 肝移植术后乙型肝炎病毒再感染的预防与诊治. 中华消化外科杂志, 2007, 6(5): 348-351.
28.	Zheng S, Chen YM, Liang TB, et al. Prevention of hepatitis B recurrence after liver transplantation using lamivudine or lamivudine combined with hepatitis B Immunoglobulin prophylaxis. Liver Transpl, 2006, 12(2): 253-258.
29.	朱建平, 李磊, 张同琳, 等. 小剂量乙型肝炎免疫球蛋白与拉米夫定联合使用对肝移植后乙肝复发的疗效. 实用临床医药杂志, 2003, 7(3): 239-242.
30.	孙丽莹, 沈中阳, 朱志军, 等. 肝移植后乙型肝炎复发的回顾性分析. 外科理论与实践, 2008, 13(4): 326-329.
31.	张相良, 朱晓峰, 石慧娟, 等. 肝移植术后乙肝复发的预防和治疗. 广东医学, 2008, 29(1): 115-117.
32.	Yoshida H, Kato T, Levi DM, et al. Lamivudine monoprophylaxis for liver transplant recipients with non-replicating hepatitis B virus infection. Clinical Transplantation, 2007, 21(2): 166-171.
33.	巫林伟, 何晓顺, 朱晓峰, 等. 乙肝免疫球蛋白预防肝移植后乙肝复发. 热带医学杂志, 2006, 6(7): 788-790.
34.	Rao W, Wu X, Xiu D. Lamivudine or lamivudine combined with hepatitis B immunoglobulin in Prophylaxis of hepatitis B recurrence after liver transplantation: a meta-analysis. Transpl Int, 2009, 22(4): 387-394.
35.	Lo CM, Fung JT, Lau GK, et al. Development of antibody to hepatitis B surfae antigen after liver transplantation for chronic hepatitis B. Hepatology, 2003, 37(1): 36-43.

1. Rohit L, Rowley AK, Wesley R, et al. Hepatitis B immunoglobulin and lamivudine improve hepatitis B related outcomes after liver transplantation: meta-analysis. Clinical Gastroenterology and Hepatolog, 2008, 6(6): 696-700.
2. Alter MJ. Epidemiology of hepatitis B in Europe and worldwide. J Hepatol, 2003, 39(Suppl 1): S64-69.
3. 全国人群乙肝血清流行病学调查结果.卫生部与中国疾病预防控制中心, 2008. http://www.chinacdc.net.cn/n272442/n272530/n3246177 /23316.html.
4. Seehofer D, Rayes N, Neuhaus P. Prophylaxis and treatment of hepatitis B recurrence after liver transplantation in the antiviral era. Expert Rev Anti Infect Ther, 2003, 1(2): 307-318.
5. Konig V, Hopf U, Neuhaus P, et al. Long-term follow-up of hepatitis B virus-infected recipients after orthotopic liver transplantation. Transplantation, 1994, 58(5): 553-559.
6. Samuel D, Muller R, Alexander G, et al. Liver transplantation in European patients with the hepatitis B surface antigen. N Engl J Med, 1993, 329(25): 1842-1847.
7. Large, muticenter, European retrospective study of more than 300 transplant patients illustrating that the risk of recurrence among patients with hepatitis B decreased with hepatitis B immunoglobulin (HBIG) usage.
8. Fontana RJ, Lok AS. Combination of HBIG and lamivudineresistant mutations: a formula for trouble? Liver Transpl, 2002, 8: 1082-1084.
9. Saab S, Kim M, Wright TL, et al. Successful orthotopic liver transplantation for lamivudine-associatied YMDD mutant hepatitis B virus. Gastroenterology, 2000, 119(5): 1382-1384.
10. Dumortier J, Le Derf Y, Guillem P, et al. Favorable outcome of livertransplantation despite a high hepatitis B virus replication: beyond the limits? Transpl Infect Dis, 2006, 8(3): 182-184.
11. Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology, 2001, 33(2): 464-470.
12. 吴泰相, 刘关键. 隐蔽分组(分配隐藏)和盲法的概念、实施与报告.中国循证医学杂志, 2007, 7(3): 222-225.
13. 王家良, 主编. 循证医学. 北京: 人民卫生出版社, 2005: 60-72.
14. Sutton AJ, Abrams KR, Jones DR, et al. Methods for meta-analysis in medical research. Wiley: Chichester, 2000.
15. Hedges LV. Modeling Publication selection effects in meta-analysis. Stat Sci, 1992, 7(2): 246-265.
16. Freshwater DA, Dudley T, Cane P, et al. Viral persistence after liver transplantation for hepatitis B virus: a cross-sectional study. Transplantation, 2008, 85(8): 1105-1111.
17. Neff,GW, O’Brien CB, Nery J, et al. Outcomes in liver transplant recipients with hepatitis B virus: Resistance and recurrence patterns from a large transplant center over the last decade. Liver Transplantation, 2004, 10(11): 1372-1378.
18. Buti M, Mas A, Prieto M, et al. Adherence to lamivudine after an early withdrawal of hepatitis B immune globulin Plays an important role in the long-term prevention of hepatitis B virus recurrence. Transplantation, 2007, 84(5): 650-654.
19. 陈耀敏, 郑树森, 王伟林, 等. 拉米夫定联合乙型肝炎免疫球蛋白防治肝移植后乙型肝炎复发的疗效研究. 浙江医学, 2008, 30(9): 989-990.
20. 朱建平, 李磊, 张同琳, 等. 拉米夫定及乙型肝炎免疫球蛋白预防肝移植后乙型肝炎复发的疗效观察. 外科理论与实践, 2003, 8(6): 479-481.
21. Zhu JP, Zhang TL, Li L, et al. Prevention and treatment of hepatitis B recurrence after liver transplantation. Hepatobillary & Pancreatic Diseases International, 2003, 2(4): 500-503.
22. Oldakowska-Jedynak U, Paczek L, Foroncewicz B, et al. Prevention of hepatitis B recurrence after liver transplantation using lamivudine and hepatitis B immune globulin. Ann Transplant, 2007, 12(3): 28-32.
23. Anselmo DM, Ghobrial RM, Jung LC, et al. New era of liver transplantation for hepatitis B: a 17-year single-center experience. Ann Surg, 2002, 235(5): 611-620.
24. 焦作义, 严律南, 李波, 等. 拉米夫定联合小剂量乙型肝炎免疫球蛋白预防肝移植术后乙型肝炎复发. 中华肝脏病杂志, 2007, 15(11): 804-808.
25. 史宪杰, 周宁新, 纪文斌, 等. 肝移植术后乙型肝炎病毒再感染的预防. 中华医院感染学杂志, 2007, 17(5): 527-529.
26. 王正昕, 丁国善, 付宏, 等. 173例肝移植术后乙型肝炎病毒再感染防治经验回顾. 中华肝胆外科杂志, 2006, 12(9): 616-618.
27. 夏杰, 杨占宇, 陈佳, 等. 肝移植术后乙型肝炎病毒再感染的预防与诊治. 中华消化外科杂志, 2007, 6(5): 348-351.
28. Zheng S, Chen YM, Liang TB, et al. Prevention of hepatitis B recurrence after liver transplantation using lamivudine or lamivudine combined with hepatitis B Immunoglobulin prophylaxis. Liver Transpl, 2006, 12(2): 253-258.
29. 朱建平, 李磊, 张同琳, 等. 小剂量乙型肝炎免疫球蛋白与拉米夫定联合使用对肝移植后乙肝复发的疗效. 实用临床医药杂志, 2003, 7(3): 239-242.
30. 孙丽莹, 沈中阳, 朱志军, 等. 肝移植后乙型肝炎复发的回顾性分析. 外科理论与实践, 2008, 13(4): 326-329.
31. 张相良, 朱晓峰, 石慧娟, 等. 肝移植术后乙肝复发的预防和治疗. 广东医学, 2008, 29(1): 115-117.
32. Yoshida H, Kato T, Levi DM, et al. Lamivudine monoprophylaxis for liver transplant recipients with non-replicating hepatitis B virus infection. Clinical Transplantation, 2007, 21(2): 166-171.
33. 巫林伟, 何晓顺, 朱晓峰, 等. 乙肝免疫球蛋白预防肝移植后乙肝复发. 热带医学杂志, 2006, 6(7): 788-790.
34. Rao W, Wu X, Xiu D. Lamivudine or lamivudine combined with hepatitis B immunoglobulin in Prophylaxis of hepatitis B recurrence after liver transplantation: a meta-analysis. Transpl Int, 2009, 22(4): 387-394.
35. Lo CM, Fung JT, Lau GK, et al. Development of antibody to hepatitis B surfae antigen after liver transplantation for chronic hepatitis B. Hepatology, 2003, 37(1): 36-43.

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拉米夫定联合乙型肝炎免疫球蛋白预防肝移植后乙肝病毒复发的系统评价

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《中国循证医学杂志》

拉米夫定联合乙型肝炎免疫球蛋白预防肝移植后乙肝病毒复发的系统评价

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