• 1.四川大學華西臨床醫(yī)學院 （成都 610041） 2.四川大學華西醫(yī)院中國循證醫(yī)學中心 （成都 610041） 3.四川大學華西醫(yī)院信息中心 4.四川大學華西醫(yī)院感染疾病中心;

目的 　評價胸腺肽α1治療HBeAg陽性慢性乙型肝炎的療效和安全性。
方法 　檢索MEDLINE，Science Citation Index，Current Content Connect，Cochrane圖書館和CBMdisc（從建庫至2005年9月15日），納入胸腺肽α1與不治療/安慰劑/支持治療比較，治療HBeAg陽性慢性乙型肝炎成年患者的隨機對照試驗（RCT）。由兩名評價員獨立評價文獻質(zhì)量和提取資料。各研究間的異質(zhì)性檢驗采用χ2檢驗和Galbraith圖，若無異質(zhì)性采用固定效應(yīng)模型合并分析，若存在使用亞組分析，敏感性分析等方法檢測導(dǎo)致異質(zhì)性的原因，并采用隨機效應(yīng)模型合并數(shù)據(jù)按療程進行亞組分析。
結(jié)果 　共納入4個試驗，HBeAg陰轉(zhuǎn)率胸腺肽α1組（38.8%）高于對照組（12.4%），兩組間差異有統(tǒng)計學意義[RR 2.22，95%CI（1.55，3.21），P=0.000]；HBV-DNA清除率胸腺肽α1組（36.9%）高于對照組（13.8%），差異有統(tǒng)計學意義[RR 2.18，95%CI（1.50，3.17），P=0.000]。短療程（8～13周）和常規(guī)療程（26～52周）的HBeAg陰轉(zhuǎn)率與HBV-DNA清除率胸腺肽α1組也均優(yōu)于對照組；胸腺肽α1組完全應(yīng)答（32.3%）高于對照組（11.3%），差異有統(tǒng)計學意義[RR 2.91，95%CI（1.71，4.94），P=0.000]；HBeAg血清轉(zhuǎn)換率和血清ALT水平復(fù)常率，兩組間差異無統(tǒng)計學意義。所有試驗未發(fā)現(xiàn)明顯不良反應(yīng)。
結(jié)論 　對HBeAg陽性慢性乙型肝炎患者，胸腺肽α1可能有使血清HBeAg和HBV-DNA陰轉(zhuǎn)效能，但對其他抗病毒指標可能無效。受原研究質(zhì)量和不同研究干預(yù)措施差異的影響，胸腺肽α1的效能尚須更多高質(zhì)量RCT予以證實。

引用本文： 周榮樂,孫 鑫,李 攀,何 林,趙連三,李幼平. 胸腺肽α1治療HBeAg陽性慢性乙型肝炎療效與安全性的隨機對照試驗的Meta分析. 中國循證醫(yī)學雜志, 2006, 06(3): 189-194. doi: 復(fù)制

1. 中華醫(yī)學會肝病學分會，中華醫(yī)學會感染病學分會. 慢性乙型肝炎防治指南. 中華肝臟病雜志, 2005; 13(12): 881~891.
2. 武宗導(dǎo), 許潔, 王功大, 等. 不同劑量胸腺肽治療慢性乙型肝炎療效觀察. 交通醫(yī)學, 2002; 16(4): 321~323.
3. 周小茜. 精制胸腺肽單用及聯(lián)用阿昔洛韋治療慢性乙型肝炎療效觀察. 四川醫(yī)學, 2002; 23(7): 720.
4. 吳鎮(zhèn)鳳, 王鐵君, 遲景新, 等. 大劑量胸腺肽對腫瘤放療病人T細胞亞群的影響. 中國免疫學雜志, 1998; 14(6): 438~439.
5. 楊朝霞, 劉微, 陳亞杰, 等. HBV-DNA定量檢測方法的評價問題. 國外醫(yī)學臨床生物化學與檢驗學分冊, 2005; 26(2): 123~124.
6. 李剛. 病毒性肝炎. 見: 楊紹基, 主編. 傳染病學 (全國高等醫(yī)藥院校七年制臨床醫(yī)學專業(yè)教材). 第1版. 北京: 人民衛(wèi)生出版社, 2002; 22~40.
7. 劉小英, 謝志軍. 大劑量胸腺肽與甘利欣聯(lián)合治療慢性乙型肝炎療效分析. 贛南醫(yī)學院學報, 2001; 21(4): 387~386.
8. Lee WM. Medical progress: hepatitis B virus infection. N Engl J Med, 1997; 337(24): 1733-1745.
9. World Health Organization. Hepatitis B. World Health Organization Fact Sheet 204 dex.(Revised October 2000).WHO Web site.Http://www.who.int/mediacentre/factsheets/fs204/en/index.html.
10. Rakesh A, Piyush R. Preventing and treating hepatitis B infection. BMJ, 2004; 329(7474): 1080-1086.
11. Liaw YF, Leung N, Guan R, et al. for the Asian-Pacific consensus update working party on chronic hepatitis B. (2005) Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2005 update. Liver International, 2005; 25(3): 472-489.
12. Hoofnagle JH, di Bisceglie AM. The treatment of chronic viral hepatitis. N Engl J Med, 1997; 336 (5)347-356.
13. Tiné F, Liberati A, Craxi A, et al. Interferon treatment in patients with chronic hepatitis B: a meta-analysis of the published literature. J Hepatol, 1993, 18(2): 154-162.
14. Sprengers D, Janssen HLA. Immunomodulatory therapy for chronic hepatitis B virus infection. Fund Clin Pharmacol, 2005; 19(1): 17-26.
15. Chang TT, Lai CL, Liaw YF, et al. Incremental increases in HBeAg seroconversion and continued ALT normalization in Asian chronic HBV patients treated with lamivudine for four years. Antivir Ther, 2000; 5(suppl 1): 44A.
16. Guan R, Lai CL, Liaw YF, et al. Eficacy and safety of 5 years lamivudine treatment of Chinese patients with chronic hepatitis B. J Gastroen hepatol, 2001; 16: A60.
17. Leung NW, Lai CL, Guan R, et al. The effect of longer duration of harbouring lamivudine-resistant hepatitis B virus (YMDD nmtants) on live histology during 3 years lamivudine therapy in Chinese patients. Hepatology, 2001; 34(2): 348A.
18. Chisari FV. Hepatitis B virus immunopathogenesis. Annu Rev Immunol, 1995; 13-: 29-60.
19. Sugahara S, Ichida T, Yamagiwa S, et al. Thymosin-alphal increases intrahepatic NK T cells and CTLs in patients with chronic hepatitis B. Hepatol Res, 2002; 24(4): 346-354.
20. Chinese Society of Hepatology , Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B. Chin J Hepatol, 2005; 13(12): 881-891.
21. Knodell MC, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology, 1981; 1(5): 431-435.
22. Baujat B, Mahe C, Pignon JP, et al. A graphical method for exploring heterogeneity in meta-analyses: application to a meta-analysis of 65 trials. Statist Med, 2002; 21(18): 2641–2652.
23. Chow WC, Ng KY, Mcscnas S, et al. The interim results of thymosin alpha 1 in a randomized controlled study in the treatment of chronic hepatitis B patients: Singapore experience. Hepatology, 1998; 28(2): 586A.
24. Wu ZD, Xu J, Wang GD, et al. The therapeutic efficacy of different dose of thymosin for treatment of chronic hepatitis B. Jiao Tong Yi Xue, 2002;16(4): 321-323.
25. Zhou XQ. Observation of efficacy of thymosin and combination with acyclovir for treatment of chronic hepatitis B. Sichuan Medical Journal, 2002; 23(7): 720.
26. Mutchnick MG, Lindsay KL, Schiff ER, et al. Thymosin a1 treatment of chronic hepatitis B: results of a phase III multicentre, randomized, double-blind and placebo controlled study. J Viral Hep, 1999; 6(5): 397-403.
27. Chien RN, Liaw YF, Chen TC, et al. Efficacy of Thymosin a1 in Patients With Chronic Hepatitis B: A Randomized, Controlled Trial. Hepatology, 1998; 27 (5): 1383-1387.
28. Wu ZF, Wang TJ, Chi JX, et al. Effect of large dose thymopeptides on T-cells of patients with tumor under radiotherapy. Chinese Journal of Immunology, 1998; 14(6): 438-439.
29. Yang CX, Liu W, Chen YJ, et al. Evaluation of methods of HBV-DNA quantitive analysis. Sect Clin Biochem &Lab Med Foreign Med Sci, 2005; 26(2): 123-124.
30. Chan HL, Tang JL, Tam W, et al. The efficacy of thymosin in the treatment of chronic hepatitis B virus infection :a meta-analysis. Aliment Pharmacol Ther, 2001; 15(12): 1899-1905.
31. Li G. Hepatitis. In: Yang SJ, ed. Infectious Diseases (textbook for the 7-year program of clinic medicine) 1st ed. Beijing: People’s Medical Publishing House, 2002; 22-40.
32. Liu XY, Xie ZJ. A study on the curative effect of combination treatment with a large amount of thymosin and potenline for chronic hepatitis B. Journal of Gannan Medical College, 2001; 21(4): 384-386.
  1. 1. 中華醫(yī)學會肝病學分會，中華醫(yī)學會感染病學分會. 慢性乙型肝炎防治指南. 中華肝臟病雜志, 2005; 13(12): 881~891.
  2. 2. 武宗導(dǎo), 許潔, 王功大, 等. 不同劑量胸腺肽治療慢性乙型肝炎療效觀察. 交通醫(yī)學, 2002; 16(4): 321~323.
  3. 3. 周小茜. 精制胸腺肽單用及聯(lián)用阿昔洛韋治療慢性乙型肝炎療效觀察. 四川醫(yī)學, 2002; 23(7): 720.
  4. 4. 吳鎮(zhèn)鳳, 王鐵君, 遲景新, 等. 大劑量胸腺肽對腫瘤放療病人T細胞亞群的影響. 中國免疫學雜志, 1998; 14(6): 438~439.
  5. 5. 楊朝霞, 劉微, 陳亞杰, 等. HBV-DNA定量檢測方法的評價問題. 國外醫(yī)學臨床生物化學與檢驗學分冊, 2005; 26(2): 123~124.
  6. 6. 李剛. 病毒性肝炎. 見: 楊紹基, 主編. 傳染病學 (全國高等醫(yī)藥院校七年制臨床醫(yī)學專業(yè)教材). 第1版. 北京: 人民衛(wèi)生出版社, 2002; 22~40.
  7. 7. 劉小英, 謝志軍. 大劑量胸腺肽與甘利欣聯(lián)合治療慢性乙型肝炎療效分析. 贛南醫(yī)學院學報, 2001; 21(4): 387~386.
  8. 8. Lee WM. Medical progress: hepatitis B virus infection. N Engl J Med, 1997; 337(24): 1733-1745.
  9. 9. World Health Organization. Hepatitis B. World Health Organization Fact Sheet 204 dex.(Revised October 2000).WHO Web site.Http://www.who.int/mediacentre/factsheets/fs204/en/index.html.
  10. 10. Rakesh A, Piyush R. Preventing and treating hepatitis B infection. BMJ, 2004; 329(7474): 1080-1086.
  11. 11. Liaw YF, Leung N, Guan R, et al. for the Asian-Pacific consensus update working party on chronic hepatitis B. (2005) Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2005 update. Liver International, 2005; 25(3): 472-489.
  12. 12. Hoofnagle JH, di Bisceglie AM. The treatment of chronic viral hepatitis. N Engl J Med, 1997; 336 (5)347-356.
  13. 13. Tiné F, Liberati A, Craxi A, et al. Interferon treatment in patients with chronic hepatitis B: a meta-analysis of the published literature. J Hepatol, 1993, 18(2): 154-162.
  14. 14. Sprengers D, Janssen HLA. Immunomodulatory therapy for chronic hepatitis B virus infection. Fund Clin Pharmacol, 2005; 19(1): 17-26.
  15. 15. Chang TT, Lai CL, Liaw YF, et al. Incremental increases in HBeAg seroconversion and continued ALT normalization in Asian chronic HBV patients treated with lamivudine for four years. Antivir Ther, 2000; 5(suppl 1): 44A.
  16. 16. Guan R, Lai CL, Liaw YF, et al. Eficacy and safety of 5 years lamivudine treatment of Chinese patients with chronic hepatitis B. J Gastroen hepatol, 2001; 16: A60.
  17. 17. Leung NW, Lai CL, Guan R, et al. The effect of longer duration of harbouring lamivudine-resistant hepatitis B virus (YMDD nmtants) on live histology during 3 years lamivudine therapy in Chinese patients. Hepatology, 2001; 34(2): 348A.
  18. 18. Chisari FV. Hepatitis B virus immunopathogenesis. Annu Rev Immunol, 1995; 13-: 29-60.
  19. 19. Sugahara S, Ichida T, Yamagiwa S, et al. Thymosin-alphal increases intrahepatic NK T cells and CTLs in patients with chronic hepatitis B. Hepatol Res, 2002; 24(4): 346-354.
  20. 20. Chinese Society of Hepatology , Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B. Chin J Hepatol, 2005; 13(12): 881-891.
  21. 21. Knodell MC, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology, 1981; 1(5): 431-435.
  22. 22. Baujat B, Mahe C, Pignon JP, et al. A graphical method for exploring heterogeneity in meta-analyses: application to a meta-analysis of 65 trials. Statist Med, 2002; 21(18): 2641–2652.
  23. 23. Chow WC, Ng KY, Mcscnas S, et al. The interim results of thymosin alpha 1 in a randomized controlled study in the treatment of chronic hepatitis B patients: Singapore experience. Hepatology, 1998; 28(2): 586A.
  24. 24. Wu ZD, Xu J, Wang GD, et al. The therapeutic efficacy of different dose of thymosin for treatment of chronic hepatitis B. Jiao Tong Yi Xue, 2002;16(4): 321-323.
  25. 25. Zhou XQ. Observation of efficacy of thymosin and combination with acyclovir for treatment of chronic hepatitis B. Sichuan Medical Journal, 2002; 23(7): 720.
  26. 26. Mutchnick MG, Lindsay KL, Schiff ER, et al. Thymosin a1 treatment of chronic hepatitis B: results of a phase III multicentre, randomized, double-blind and placebo controlled study. J Viral Hep, 1999; 6(5): 397-403.
  27. 27. Chien RN, Liaw YF, Chen TC, et al. Efficacy of Thymosin a1 in Patients With Chronic Hepatitis B: A Randomized, Controlled Trial. Hepatology, 1998; 27 (5): 1383-1387.
  28. 28. Wu ZF, Wang TJ, Chi JX, et al. Effect of large dose thymopeptides on T-cells of patients with tumor under radiotherapy. Chinese Journal of Immunology, 1998; 14(6): 438-439.
  29. 29. Yang CX, Liu W, Chen YJ, et al. Evaluation of methods of HBV-DNA quantitive analysis. Sect Clin Biochem &Lab Med Foreign Med Sci, 2005; 26(2): 123-124.
  30. 30. Chan HL, Tang JL, Tam W, et al. The efficacy of thymosin in the treatment of chronic hepatitis B virus infection :a meta-analysis. Aliment Pharmacol Ther, 2001; 15(12): 1899-1905.
  31. 31. Li G. Hepatitis. In: Yang SJ, ed. Infectious Diseases (textbook for the 7-year program of clinic medicine) 1st ed. Beijing: People’s Medical Publishing House, 2002; 22-40.
  32. 32. Liu XY, Xie ZJ. A study on the curative effect of combination treatment with a large amount of thymosin and potenline for chronic hepatitis B. Journal of Gannan Medical College, 2001; 21(4): 384-386.