• 四川大學華西醫(yī)院循證醫(yī)學與臨床流行病學中心（成都 610041）;

目的 　系統(tǒng)評價當前研究血清透明質(zhì)酸診斷肝纖維化文獻的質(zhì)量，分析偏倚和變異產(chǎn)生的來源，并了解血清透明質(zhì)酸對診斷慢性病毒性肝炎所致早期肝硬化、肝纖維化的準確性。
方法　 采用計算機和手工檢索全面收集當前研究血清透明質(zhì)酸對慢性病毒性肝炎所致肝纖維化的診斷性試驗文獻，并根據(jù)QUADAS（quality assessment of diagnostic accuracy studies）質(zhì)量評價標準評價符合納入標準的文獻的質(zhì)量，用Meta-disc軟件對敏感性、特異性、陽性似然比（+LR）、陰性似然比（-LR）、診斷性試驗比值比等進行合并分析和異質(zhì)性檢驗，對無異質(zhì)性的文獻用DPS2005軟件繪制SROC曲線。
結果 　共納入符合納入標準的文獻24篇，其中中、英文文獻各占一半。在合并分析中，放射免疫法診斷肝硬化文獻，以及區(qū)分有無肝纖維化的文獻合并+LR分別為7.029、3.608；合并-LR分別為0.198、0.319。酶聯(lián)免疫法中，診斷肝硬化的文獻、鑒別輕、重度肝纖維化的文獻，區(qū)分有無肝纖維化的文獻的合并+LR分別為6.093、9.806和4.308；合并-LR分別為0.354、0.347和0.563。
結論 　本系統(tǒng)評價所納入24篇文獻的偏倚主要來自參考標準判讀時未實施盲法，存在變異的可能性較大，報告質(zhì)量較差。放射免疫法和酶聯(lián)免疫法血清透明質(zhì)酸對肝硬化具有較好的診斷價值，對有無肝纖維化的判別價值也可認可，但該兩種檢測方法在鑒別輕、重度肝纖維化的診斷價值尚需進一步研究。

引用本文： 張雅,劉關鍵,吳泰相. 血清透明質(zhì)酸對慢性病毒性肝炎肝纖維化診斷價值的系統(tǒng)評價. 中國循證醫(yī)學雜志, 2007, 07(2): 112-120. doi: 復制

1. Wang BE, Zhang DF, editor-in-chief. Modern study of liver disease. 1st edition. BeiJing: Science Press, 2003; 513.
2. Luo KX, editor in chief. Hepatitis B-basic and clinical. 1st edition. BeiJing: People’s Health Press, 1997; 370.
3. Xie SB, Chen YM, Xie DY, et al. Clinical significance of serum hyaluronic acid in the diagnosis of hepatic fibrosis. Academic Journal of Sun Yat-sen University of Medical Sciences, 1998, 19(3): 211–213.
4. Jian XY; Zheng GA; Liao XH, et al, The study on evaluating fibrosis degrees and diagnosing liver cirrhosis by combining ultrasonography and serology. Medicine Industry Information, 2006; 3(11): 7–9.
5. Chen YP, Feng XR, Dai L, et al. Screening and evaluation of non-invasive diagnosis markers for compensated liver cirrhosis in patients with chronic hepatitis B. Chinese Journal of Hepatology, 2003; 11(4): 225–227.
6. Zhang M, Zhang LX, Zhao JM, et al. Evaluation of several serum markers for liver fibrosis in patients with viral hepatitis. Infections Disease Information, 2001; 14(2): 69–70, 57.
7. Wang YQ. Analysis of the Correlation between Serum Markers and Pathology of Chronic Hepatitis. The Journal of Medical Theory and Practice, 2001; 14(11): 1093–1094.
8. Chen Y, Duan ZP, Wang BE, et al. Serological diagnosis of early liver cirrhosis. Clinical Focus, 2003; 18(20): 1151–1153.
9. Dong HY, Li Y, Zhao GM. The Contrast Study of Serum Liver Fibrosis Indexes and Liver Pathology. Chinese Journal of Clinical Gastroenterology, 2006; 18(2): 93–94.
10. Cai WM, Zhang BB, Weng HL, et al. The diagnostic value of eight serum indices for liver fibrosis. Chinese Journal of Hepatology, 2004; 12(4): 219–222.
11. Gu Lixiang, Jiang Shenyung, He Wei fang, et al. The Values of PGA Index and HA in Diagnosis of Fibrosis in the Liver with Chronic Hepatitis B. Clinical Medical Journal of China, 2002; 9(5): 496–498.
12. Zheng M, Cai WM, Weng HL, et al. ROC curve in evaluation of serum fibrosis index for diagnosing hepatic fibrosis. Chinese Journal of Infectious Diseases, 2002; 20(4): 225–228.
13. Hao JH, Zou JW, Gao P. Clinical Study of serum hyaluronic acid, type IV collagen and laminin. Shangdong Medicine, 1999; 39(3): 1–2.
14. Zhang SL, Yang YP, Chen DY, et al. Diagnostic significance of serum hyaluronic acid, type III collagen aminopeptide, type IV collagen, laminin and PGA index for hepatic fibrosis. Chinese Journal Infectious Disease, 1999; 17(4): 261–262.
15. 王寶恩, 張定鳳, 主編. 現(xiàn)代肝臟病學. 第1版. 北京: 科學出版社, 2003; 513.
16. 駱抗先, 主編. 乙型肝炎－基礎和臨床. 第1版. 北京: 人民衛(wèi)生出版社, 1997; 370.
17. Poynard T, Munteanu M, Imbert-Bismut F, et al. Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C. Clinical chemistry, 2004; 50(8): 1344–1355.
18. Lichtinghagen R, Bahr M. Noninvasive diagnosis of fibrosis in chronic liver disease. Expert. Rev. Mol. Diagn. 2004, 4(5): 715–726.
19. Battaglia M, Bucher H, Egger M, et al. The Bayes Library of Diagnostic Studies and Reviews. 2nd edition. 2002.
20. Whiting P, Rutjes AW, Reitsma JB, et al. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC medical research methodology, 2003: 3: 25.
21. 謝仕斌, 陳幼明, 謝冬英, 等. 血清透明質(zhì)酸測定對肝纖維化診斷的臨床意義. 中山醫(yī)科大學學報, 1998; 19(3): 211～213.
22. 簡希堯, 鄭國安, 廖小輝, 馬松炎. 血清纖維化指標與超聲聯(lián)合評價肝纖維化程度的研究. 國藥產(chǎn)業(yè)資訊, 2006; 3(11): 7～9.
23. 陳永鵬, 馮筱榕, 戴琳, 等. 代償性肝硬化無創(chuàng)性診斷指標的篩選及評價. 中華肝臟病雜志, 2003; 11(4): 225～227.
24. 張敏, 張玲霞, 趙景民, 等. 慢性病毒性肝炎血清纖維化診斷指標評估. 傳染病信息, 2001; 14(2): 69～70, 57.
25. Plevris JN, Haydon GH, Simpson KJ, et al. Serum hyaluronan-A non-invasive test for diagnosing liver cirrhosis. European Journal of Gastroenterology and Hepatology, 2000; 12(10 ): 1121–1127.
26. McHutchison JG, Blatt LM, De Medina M, et al. Measurement of serum hyaluronic acid in patients with chronic hepatitis C and its relationship to liver histology. Journal of Gastroenterology and Hepatology, 2000; 15(8): 945–951.
27. Guechot J, Laudat A, Loria A, et al. Diagnostic accuracy of hyaluronan and type III procollagen amino-terminal peptide serum assays as markers of liver fibrosis in chronic viral hepatitis C evaluated by ROC curve analysis. Clinical Chemistry, 1996; 42(4): 558–563.
28. 王迎秋. 血清指標與慢性肝炎病理關系分析. 醫(yī)學理論與實踐, 2001; 14(11): 1093～1094.
29. 陳煜, 段鐘平, 王寶恩, 等. 早期肝硬化的血清學診斷臨床研究. 臨床薈萃, 2003; 18(20): 1151～1153.
30. Gordon A, Bailey MJ, Gibson PR, et al. Comprehensive clinical assessment improves the accuracy of predicting cirrhosis in chronic hepatitis C. Journal of Gastroenterology and Hepatology, 2005; 20(6): 825–832.
31. Murawaki Y, Ikuta Y, Koda M, et al. Clinical significance of serum hyaluronan in patients with chronic viral liver disease. Journal of Gastroenterology and Hepatology, 1996; 11(5): 459–465.
32. Halfon P, Bourliere M, Penaranda G, et al. Accuracy of hyaluronic acid level for predicting liver fibrosis stages in patients with hepatitis C virus. Comparative Hepatology, 2005; 4: - (7p) .
33. Montazeri G, Estakhri A, Mohamadnejad M, et al. Serum hyaluronate as a non-invasive marker of hepatic fibrosis and inflammation in HBeAg-negative chronic hepatitis B. BMC Gastroenterology, 2005; 5:- (24p).
34. Leroy V, Monier F, Bottari S, et al. Circulating Matrix Metalloproteinases 1, 2, 9 and Their Inhibitors TIMP-1 and TIMP-2 as Serum Markers of Liver Fibrosis in Patients with Chronic Hepatitis C: Comparison with PIIINP and Hyaluronic Acid. American Journal of Gastroenterology, 2004; 99(2): 271–279.
35. Murawaki Y, Ikuta Y, Okamoto K, et al. Diagnostic value of serum markers of connective tissue turnover for predicting histological staging and grading in patients with chronic hepatitis C. Journal of Gastroenterology, 2001; 36(6): 399–406.
36. Wong VS, Hughes V, Trull A, et al. Serum hyaluronic acid is a useful marker of liver fibrosis in chronic hepatitis C virus infection. Journal of Viral Hepatitis, 1998; 5(3): 187–192.
37. 董紅筠, 李穎, 趙桂鳴. 血清肝纖維化指標與肝臟病理學對照觀察. 臨床消化病雜志, 2006; 18(2): 93～94.
38. 蔡衛(wèi)民, 張彬彬, 翁紅雷, 等. 八項肝纖維化血清標志物比較研究. 中華肝臟病雜志, 2004; 12(4): 219～222.
39. 顧立祥, 江圣勇, 何偉芳, 等. PGA指數(shù)和透明質(zhì)酸在診斷慢性乙肝肝纖維化中的價值. 中國臨床醫(yī)學, 2002; 9(5): 496～498.
40. 鄭敏, 蔡衛(wèi)民, 翁紅雷, 等. ROC 曲線評價血清纖維化指標對診斷肝纖維化的價值. 中華傳染病雜志, 2002; 20(4): 225～228.
41. 郝菁華, 鄒建文, 高鵬. 血清透明質(zhì)酸、IV型膠原及層連蛋白檢測的臨床應用研究. 山東醫(yī)藥, 1999; 39(3): 1～2.
42. 張世蘭, 楊永平, 陳德永, 等. 血清透明質(zhì)酸、III型膠原氨基肽、IV型膠原及層粘蛋白與PGA指數(shù)對肝纖維化的診斷意義. 中華傳染病雜志, 1999; 17(4): 261～262.
43. Zhang BB, Cai WM, Weng HL, et al. Diagnostic value of platelet derived growth factor-BB, transforming growth factor-(beta)(1), matrix metalloproteinase-1, and tissue inhibitor of matrix metalloproteinase-1 in serum and peripheral blood monoclear cells for hepatic fibrosis. World Journal of Gastroenterology, 2003; 9(11): 2490–2496.
44. .Zheng M, Cai WM, Weng HL, et al. ROC curves in evaluation of serum fibrosis indices for hepatic fibrosis. World Journal of Gastroenterology, 2002; 8(6): 1073–1076.
45. Kozlowska J, Jablonska J, Cianciara J, et al. Biochemical markers of liver fibrosis in patients with chronic hepatitis C. Gastroenterologia Polska, 2006; 13(2 ): 97–102.
46. Adams LA, Bulsara M, Rossi E, et al. Hepascore: An accurate validated predictor of liver fibrosis in chronic hepatitis C infection. Clinical Chemistry, 2005; 51(10): 1867–1873.
47. Adler M, Frotscher B, Thiry Ph, et al. Non invasive markers of liver fibrosis in hepatitis C. Acta Gastro-Enterologica Belgica, 2004; 67(3): 278–281.
48. Xie SB, Yao JL, Zheng RQ, et al. Serum hyaluronic acid, procollagen type III and IV in histological diagnosis of liver fibrosis. Hepatobiliary and Pancreatic Diseases International, 2003; 2(1): 69–72.
49. Patrick M, Bossuyt JB, Reitsma DE, et al. The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Croat Med J, 2003; 44: 639–650.
  1. 1. Wang BE, Zhang DF, editor-in-chief. Modern study of liver disease. 1st edition. BeiJing: Science Press, 2003; 513.
  2. 2. Luo KX, editor in chief. Hepatitis B-basic and clinical. 1st edition. BeiJing: People’s Health Press, 1997; 370.
  3. 3. Xie SB, Chen YM, Xie DY, et al. Clinical significance of serum hyaluronic acid in the diagnosis of hepatic fibrosis. Academic Journal of Sun Yat-sen University of Medical Sciences, 1998, 19(3): 211–213.
  4. 4. Jian XY; Zheng GA; Liao XH, et al, The study on evaluating fibrosis degrees and diagnosing liver cirrhosis by combining ultrasonography and serology. Medicine Industry Information, 2006; 3(11): 7–9.
  5. 5. Chen YP, Feng XR, Dai L, et al. Screening and evaluation of non-invasive diagnosis markers for compensated liver cirrhosis in patients with chronic hepatitis B. Chinese Journal of Hepatology, 2003; 11(4): 225–227.
  6. 6. Zhang M, Zhang LX, Zhao JM, et al. Evaluation of several serum markers for liver fibrosis in patients with viral hepatitis. Infections Disease Information, 2001; 14(2): 69–70, 57.
  7. 7. Wang YQ. Analysis of the Correlation between Serum Markers and Pathology of Chronic Hepatitis. The Journal of Medical Theory and Practice, 2001; 14(11): 1093–1094.
  8. 8. Chen Y, Duan ZP, Wang BE, et al. Serological diagnosis of early liver cirrhosis. Clinical Focus, 2003; 18(20): 1151–1153.
  9. 9. Dong HY, Li Y, Zhao GM. The Contrast Study of Serum Liver Fibrosis Indexes and Liver Pathology. Chinese Journal of Clinical Gastroenterology, 2006; 18(2): 93–94.
  10. 10. Cai WM, Zhang BB, Weng HL, et al. The diagnostic value of eight serum indices for liver fibrosis. Chinese Journal of Hepatology, 2004; 12(4): 219–222.
  11. 11. Gu Lixiang, Jiang Shenyung, He Wei fang, et al. The Values of PGA Index and HA in Diagnosis of Fibrosis in the Liver with Chronic Hepatitis B. Clinical Medical Journal of China, 2002; 9(5): 496–498.
  12. 12. Zheng M, Cai WM, Weng HL, et al. ROC curve in evaluation of serum fibrosis index for diagnosing hepatic fibrosis. Chinese Journal of Infectious Diseases, 2002; 20(4): 225–228.
  13. 13. Hao JH, Zou JW, Gao P. Clinical Study of serum hyaluronic acid, type IV collagen and laminin. Shangdong Medicine, 1999; 39(3): 1–2.
  14. 14. Zhang SL, Yang YP, Chen DY, et al. Diagnostic significance of serum hyaluronic acid, type III collagen aminopeptide, type IV collagen, laminin and PGA index for hepatic fibrosis. Chinese Journal Infectious Disease, 1999; 17(4): 261–262.
  15. 15. 王寶恩, 張定鳳, 主編. 現(xiàn)代肝臟病學. 第1版. 北京: 科學出版社, 2003; 513.
  16. 16. 駱抗先, 主編. 乙型肝炎－基礎和臨床. 第1版. 北京: 人民衛(wèi)生出版社, 1997; 370.
  17. 17. Poynard T, Munteanu M, Imbert-Bismut F, et al. Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C. Clinical chemistry, 2004; 50(8): 1344–1355.
  18. 18. Lichtinghagen R, Bahr M. Noninvasive diagnosis of fibrosis in chronic liver disease. Expert. Rev. Mol. Diagn. 2004, 4(5): 715–726.
  19. 19. Battaglia M, Bucher H, Egger M, et al. The Bayes Library of Diagnostic Studies and Reviews. 2nd edition. 2002.
  20. 20. Whiting P, Rutjes AW, Reitsma JB, et al. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC medical research methodology, 2003: 3: 25.
  21. 21. 謝仕斌, 陳幼明, 謝冬英, 等. 血清透明質(zhì)酸測定對肝纖維化診斷的臨床意義. 中山醫(yī)科大學學報, 1998; 19(3): 211～213.
  22. 22. 簡希堯, 鄭國安, 廖小輝, 馬松炎. 血清纖維化指標與超聲聯(lián)合評價肝纖維化程度的研究. 國藥產(chǎn)業(yè)資訊, 2006; 3(11): 7～9.
  23. 23. 陳永鵬, 馮筱榕, 戴琳, 等. 代償性肝硬化無創(chuàng)性診斷指標的篩選及評價. 中華肝臟病雜志, 2003; 11(4): 225～227.
  24. 24. 張敏, 張玲霞, 趙景民, 等. 慢性病毒性肝炎血清纖維化診斷指標評估. 傳染病信息, 2001; 14(2): 69～70, 57.
  25. 25. Plevris JN, Haydon GH, Simpson KJ, et al. Serum hyaluronan-A non-invasive test for diagnosing liver cirrhosis. European Journal of Gastroenterology and Hepatology, 2000; 12(10 ): 1121–1127.
  26. 26. McHutchison JG, Blatt LM, De Medina M, et al. Measurement of serum hyaluronic acid in patients with chronic hepatitis C and its relationship to liver histology. Journal of Gastroenterology and Hepatology, 2000; 15(8): 945–951.
  27. 27. Guechot J, Laudat A, Loria A, et al. Diagnostic accuracy of hyaluronan and type III procollagen amino-terminal peptide serum assays as markers of liver fibrosis in chronic viral hepatitis C evaluated by ROC curve analysis. Clinical Chemistry, 1996; 42(4): 558–563.
  28. 28. 王迎秋. 血清指標與慢性肝炎病理關系分析. 醫(yī)學理論與實踐, 2001; 14(11): 1093～1094.
  29. 29. 陳煜, 段鐘平, 王寶恩, 等. 早期肝硬化的血清學診斷臨床研究. 臨床薈萃, 2003; 18(20): 1151～1153.
  30. 30. Gordon A, Bailey MJ, Gibson PR, et al. Comprehensive clinical assessment improves the accuracy of predicting cirrhosis in chronic hepatitis C. Journal of Gastroenterology and Hepatology, 2005; 20(6): 825–832.
  31. 31. Murawaki Y, Ikuta Y, Koda M, et al. Clinical significance of serum hyaluronan in patients with chronic viral liver disease. Journal of Gastroenterology and Hepatology, 1996; 11(5): 459–465.
  32. 32. Halfon P, Bourliere M, Penaranda G, et al. Accuracy of hyaluronic acid level for predicting liver fibrosis stages in patients with hepatitis C virus. Comparative Hepatology, 2005; 4: - (7p) .
  33. 33. Montazeri G, Estakhri A, Mohamadnejad M, et al. Serum hyaluronate as a non-invasive marker of hepatic fibrosis and inflammation in HBeAg-negative chronic hepatitis B. BMC Gastroenterology, 2005; 5:- (24p).
  34. 34. Leroy V, Monier F, Bottari S, et al. Circulating Matrix Metalloproteinases 1, 2, 9 and Their Inhibitors TIMP-1 and TIMP-2 as Serum Markers of Liver Fibrosis in Patients with Chronic Hepatitis C: Comparison with PIIINP and Hyaluronic Acid. American Journal of Gastroenterology, 2004; 99(2): 271–279.
  35. 35. Murawaki Y, Ikuta Y, Okamoto K, et al. Diagnostic value of serum markers of connective tissue turnover for predicting histological staging and grading in patients with chronic hepatitis C. Journal of Gastroenterology, 2001; 36(6): 399–406.
  36. 36. Wong VS, Hughes V, Trull A, et al. Serum hyaluronic acid is a useful marker of liver fibrosis in chronic hepatitis C virus infection. Journal of Viral Hepatitis, 1998; 5(3): 187–192.
  37. 37. 董紅筠, 李穎, 趙桂鳴. 血清肝纖維化指標與肝臟病理學對照觀察. 臨床消化病雜志, 2006; 18(2): 93～94.
  38. 38. 蔡衛(wèi)民, 張彬彬, 翁紅雷, 等. 八項肝纖維化血清標志物比較研究. 中華肝臟病雜志, 2004; 12(4): 219～222.
  39. 39. 顧立祥, 江圣勇, 何偉芳, 等. PGA指數(shù)和透明質(zhì)酸在診斷慢性乙肝肝纖維化中的價值. 中國臨床醫(yī)學, 2002; 9(5): 496～498.
  40. 40. 鄭敏, 蔡衛(wèi)民, 翁紅雷, 等. ROC 曲線評價血清纖維化指標對診斷肝纖維化的價值. 中華傳染病雜志, 2002; 20(4): 225～228.
  41. 41. 郝菁華, 鄒建文, 高鵬. 血清透明質(zhì)酸、IV型膠原及層連蛋白檢測的臨床應用研究. 山東醫(yī)藥, 1999; 39(3): 1～2.
  42. 42. 張世蘭, 楊永平, 陳德永, 等. 血清透明質(zhì)酸、III型膠原氨基肽、IV型膠原及層粘蛋白與PGA指數(shù)對肝纖維化的診斷意義. 中華傳染病雜志, 1999; 17(4): 261～262.
  43. 43. Zhang BB, Cai WM, Weng HL, et al. Diagnostic value of platelet derived growth factor-BB, transforming growth factor-(beta)(1), matrix metalloproteinase-1, and tissue inhibitor of matrix metalloproteinase-1 in serum and peripheral blood monoclear cells for hepatic fibrosis. World Journal of Gastroenterology, 2003; 9(11): 2490–2496.
  44. 44. .Zheng M, Cai WM, Weng HL, et al. ROC curves in evaluation of serum fibrosis indices for hepatic fibrosis. World Journal of Gastroenterology, 2002; 8(6): 1073–1076.
  45. 45. Kozlowska J, Jablonska J, Cianciara J, et al. Biochemical markers of liver fibrosis in patients with chronic hepatitis C. Gastroenterologia Polska, 2006; 13(2 ): 97–102.
  46. 46. Adams LA, Bulsara M, Rossi E, et al. Hepascore: An accurate validated predictor of liver fibrosis in chronic hepatitis C infection. Clinical Chemistry, 2005; 51(10): 1867–1873.
  47. 47. Adler M, Frotscher B, Thiry Ph, et al. Non invasive markers of liver fibrosis in hepatitis C. Acta Gastro-Enterologica Belgica, 2004; 67(3): 278–281.
  48. 48. Xie SB, Yao JL, Zheng RQ, et al. Serum hyaluronic acid, procollagen type III and IV in histological diagnosis of liver fibrosis. Hepatobiliary and Pancreatic Diseases International, 2003; 2(1): 69–72.
  49. 49. Patrick M, Bossuyt JB, Reitsma DE, et al. The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Croat Med J, 2003; 44: 639–650.