拉米夫定聯合乙型肝炎免疫球蛋白預防肝移植后乙肝病毒復發的系統評價_《中國循證醫學雜志》

作者：

江自成 ,  江建寧

廣西醫科大學第一附屬醫院感染性疾病科（南寧 530021）;

關鍵詞：

肝移植乙型肝炎病毒復發拉米夫定乙型肝炎高效價免疫球蛋白 Meta分析

DOI：

10.7507/1672-2531.20100527

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目的 ?評價拉米夫定（lamivudine，LAM）聯合乙型肝炎免疫球蛋白（hepatitis B immunoglobulin，HBIG）預防肝移植后乙肝病毒復發的價值。
方法 ?計算機檢索MEDLINE（Ovid）、PubMed、EMbase、CENTRAL（Cochrane Central Register of Controlled Trials）、CBM、CNKI、VIP關于LAM聯合HBIG與LAM單用預防肝移植后乙肝病毒復發的隨機雙盲對照、非隨機同期對照及病例對照研究。檢索時間截至2008年12月。兩名研究者獨立按Cochrane系統評價方法選擇試驗、提取資料，并采用RevMan 5.0.18軟件進行Meta分析。
結果? 共納入11項研究，均為非隨機同期對照試驗，共1 421例患者，其中LAM聯合HBIG組1 035例，LAM單用組386例。結果顯示，LAM聯合HBIG治療組較單用LAM治療組：① 減少乙肝病毒復發風險達73%［RR=0.27，95%CI（0.20，0.37），P lt;0.000 01］；② 減少乙肝病毒YMDD變異風險達72%［RR=0.28，95%CI（0.15，0.53），P=0.000 01］；③ 減少乙肝病毒復發所致的死亡風險達79%［RR=0.21，95%CI（0.09，0.49），P=0.000 3］；④ 受者和移植物總的生存率兩組相似［RR=1.03，95%CI（0.95，1.11），P=0.51；RR=1.04，95%CI（0.97，1.12），P=0.26］。
結論 ?現有研究顯示LAM聯合HBIG治療比LAM單用可明顯減少肝移植后乙肝病毒復發、發生YMDD變異及乙肝病毒復發所致的死亡風險。LAM聯合HBIG是預防肝移植后乙肝病毒復發的有效措施。

引用本文： 江自成,江建寧. 拉米夫定聯合乙型肝炎免疫球蛋白預防肝移植后乙肝病毒復發的系統評價. 中國循證醫學雜志, 2010, 10(8): 964-971. doi: 10.7507/1672-2531.20100527 復制

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.	全國人群乙肝血清流行病學調查結果.衛生部與中國疾病預防控制中心, 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.	吳泰相, 劉關鍵. 隱蔽分組(分配隱藏)和盲法的概念、實施與報告.中國循證醫學雜志, 2007, 7(3): 222-225.
13.	王家良, 主編. 循證醫學. 北京: 人民衛生出版社, 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.	陳耀敏, 鄭樹森, 王偉林, 等. 拉米夫定聯合乙型肝炎免疫球蛋白防治肝移植后乙型肝炎復發的療效研究. 浙江醫學, 2008, 30(9): 989-990.
20.	朱建平, 李磊, 張同琳, 等. 拉米夫定及乙型肝炎免疫球蛋白預防肝移植后乙型肝炎復發的療效觀察. 外科理論與實踐, 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.	焦作義, 嚴律南, 李波, 等. 拉米夫定聯合小劑量乙型肝炎免疫球蛋白預防肝移植術后乙型肝炎復發. 中華肝臟病雜志, 2007, 15(11): 804-808.
25.	史憲杰, 周寧新, 紀文斌, 等. 肝移植術后乙型肝炎病毒再感染的預防. 中華醫院感染學雜志, 2007, 17(5): 527-529.
26.	王正昕, 丁國善, 付宏, 等. 173例肝移植術后乙型肝炎病毒再感染防治經驗回顧. 中華肝膽外科雜志, 2006, 12(9): 616-618.
27.	夏杰, 楊占宇, 陳佳, 等. 肝移植術后乙型肝炎病毒再感染的預防與診治. 中華消化外科雜志, 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, 張同琳, 等. 小劑量乙型肝炎免疫球蛋白與拉米夫定聯合使用對肝移植后乙肝復發的療效. 實用臨床醫藥雜志, 2003, 7(3): 239-242.
30.	孫麗瑩, 沈中陽, 朱志軍, 等. 肝移植后乙型肝炎復發的回顧性分析. 外科理論與實踐, 2008, 13(4): 326-329.
31.	張相良, 朱曉峰, 石慧娟, 等. 肝移植術后乙肝復發的預防和治療. 廣東醫學, 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.	巫林偉, 何曉順, 朱曉峰, 等. 乙肝免疫球蛋白預防肝移植后乙肝復發. 熱帶醫學雜志, 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. 全國人群乙肝血清流行病學調查結果.衛生部與中國疾病預防控制中心, 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. 吳泰相, 劉關鍵. 隱蔽分組(分配隱藏)和盲法的概念、實施與報告.中國循證醫學雜志, 2007, 7(3): 222-225.
13. 王家良, 主編. 循證醫學. 北京: 人民衛生出版社, 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. 陳耀敏, 鄭樹森, 王偉林, 等. 拉米夫定聯合乙型肝炎免疫球蛋白防治肝移植后乙型肝炎復發的療效研究. 浙江醫學, 2008, 30(9): 989-990.
20. 朱建平, 李磊, 張同琳, 等. 拉米夫定及乙型肝炎免疫球蛋白預防肝移植后乙型肝炎復發的療效觀察. 外科理論與實踐, 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. 焦作義, 嚴律南, 李波, 等. 拉米夫定聯合小劑量乙型肝炎免疫球蛋白預防肝移植術后乙型肝炎復發. 中華肝臟病雜志, 2007, 15(11): 804-808.
25. 史憲杰, 周寧新, 紀文斌, 等. 肝移植術后乙型肝炎病毒再感染的預防. 中華醫院感染學雜志, 2007, 17(5): 527-529.
26. 王正昕, 丁國善, 付宏, 等. 173例肝移植術后乙型肝炎病毒再感染防治經驗回顧. 中華肝膽外科雜志, 2006, 12(9): 616-618.
27. 夏杰, 楊占宇, 陳佳, 等. 肝移植術后乙型肝炎病毒再感染的預防與診治. 中華消化外科雜志, 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, 張同琳, 等. 小劑量乙型肝炎免疫球蛋白與拉米夫定聯合使用對肝移植后乙肝復發的療效. 實用臨床醫藥雜志, 2003, 7(3): 239-242.
30. 孫麗瑩, 沈中陽, 朱志軍, 等. 肝移植后乙型肝炎復發的回顧性分析. 外科理論與實踐, 2008, 13(4): 326-329.
31. 張相良, 朱曉峰, 石慧娟, 等. 肝移植術后乙肝復發的預防和治療. 廣東醫學, 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. 巫林偉, 何曉順, 朱曉峰, 等. 乙肝免疫球蛋白預防肝移植后乙肝復發. 熱帶醫學雜志, 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.

《中國循證醫學雜志》

拉米夫定聯合乙型肝炎免疫球蛋白預防肝移植后乙肝病毒復發的系統評價

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《中國循證醫學雜志》

拉米夫定聯合乙型肝炎免疫球蛋白預防肝移植后乙肝病毒復發的系統評價

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