The Diagnostic Value of Serum Hyaluronic Acid for Liver Fibrosis in Patients with Chronic Viral Hepatitis: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

ZHANG Ya ,  LIU Guanjian , WU Taixiang

Evidence-based Medicine and Clinical Epidemiology Center, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

LIU Guanjian, Email: ersi2004120@126.com

Keywords：

血清透明质酸; 慢性病毒性肝炎; 肝纤维化; 诊断性试验; 质量评价; 系统评价

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Objective 　To evaluate the quality of studies assessing the value of serum hyaluronic acid in the diagnosis of liver fibrosis, to analyze the sources of bias and variation, and to estimate the accuracy of serum hyaluronic acid in diagnosing early liver cirrhosis and liver fibrosis in patients with chronic viral hepatitis.
Methods 　We searched MEDLINE (1966 to June 2006), EMbase (1974 to June 2006), CBMdisc (1978 to April 2005), CNKI (2005 to June 2006) and VIP (2005 to June 2006) for studies assessing the diagnostic value of serum hyaluronic acid for liver fibrosis in patients with chronic viral hepatitis. We checked the references in the reports of included studies. QUADAS items were used for quality assessment. Meta-disc software was used to analyze sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic test odds ratio for the pooled analysis and heterogeneity test. DPS2005 software was used to draw SROC curves for those without heterogeneity.
Results 　In total 24 studies were included: 12 published in Chinese and 12 published in English. Results of the pooled analysis showed that, as for radioimmunoassay (RIA), the pooled LR+ of the studies involving the diagnosis of liver cirrhosis and the differentiation of absent/present liver fibrosis were 7.029 and 3.608; and the pooled LR- were 0.198 and 0.319, respectively. As for enzyme-linked immunosorbent assay (ELISA), the pooled LR+ of the studies involving the diagnosis of liver cirrhosis, the differentiation of mild/severe and absent/present liver fibrosis were 6.093, 9.806 and 4.308; and the pooled LR- were 0.354, 0.347 and 0.563, respectively.
Conclusion 　The biases identified from the 24 studies are mainly due to reference standard review bias. By both RIA and ELISA methods, serum hyaluronic acid has a sound value in diagnosing live cirrhosis. Its value in differentiating absent/present liver fibrosis is also acceptable. However, its value in differentiating mild/severe liver fibrosis needs to be further studied.

Citation： ZHANG Ya,LIU Guanjian,WU Taixiang. The Diagnostic Value of Serum Hyaluronic Acid for Liver Fibrosis in Patients with Chronic Viral Hepatitis: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2007, 07(2): 112-120. doi: Copy

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.	王宝恩, 张定凤, 主编. 现代肝脏病学. 第1版. 北京: 科学出版社, 2003; 513.
16.	骆抗先, 主编. 乙型肝炎－基础和临床. 第1版. 北京: 人民卫生出版社, 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.	谢仕斌, 陈幼明, 谢冬英, 等. 血清透明质酸测定对肝纤维化诊断的临床意义. 中山医科大学学报, 1998; 19(3): 211～213.
22.	简希尧, 郑国安, 廖小辉, 马松炎. 血清纤维化指标与超声联合评价肝纤维化程度的研究. 国药产业资讯, 2006; 3(11): 7～9.
23.	陈永鹏, 冯筱榕, 戴琳, 等. 代偿性肝硬化无创性诊断指标的筛选及评价. 中华肝脏病杂志, 2003; 11(4): 225～227.
24.	张敏, 张玲霞, 赵景民, 等. 慢性病毒性肝炎血清纤维化诊断指标评估. 传染病信息, 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. 血清指标与慢性肝炎病理关系分析. 医学理论与实践, 2001; 14(11): 1093～1094.
29.	陈煜, 段钟平, 王宝恩, 等. 早期肝硬化的血清学诊断临床研究. 临床荟萃, 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.	董红筠, 李颖, 赵桂鸣. 血清肝纤维化指标与肝脏病理学对照观察. 临床消化病杂志, 2006; 18(2): 93～94.
38.	蔡卫民, 张彬彬, 翁红雷, 等. 八项肝纤维化血清标志物比较研究. 中华肝脏病杂志, 2004; 12(4): 219～222.
39.	顾立祥, 江圣勇, 何伟芳, 等. PGA指数和透明质酸在诊断慢性乙肝肝纤维化中的价值. 中国临床医学, 2002; 9(5): 496～498.
40.	郑敏, 蔡卫民, 翁红雷, 等. ROC 曲线评价血清纤维化指标对诊断肝纤维化的价值. 中华传染病杂志, 2002; 20(4): 225～228.
41.	郝菁华, 邹建文, 高鹏. 血清透明质酸、IV型胶原及层连蛋白检测的临床应用研究. 山东医药, 1999; 39(3): 1～2.
42.	张世兰, 杨永平, 陈德永, 等. 血清透明质酸、III型胶原氨基肽、IV型胶原及层粘蛋白与PGA指数对肝纤维化的诊断意义. 中华传染病杂志, 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. 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. 王宝恩, 张定凤, 主编. 现代肝脏病学. 第1版. 北京: 科学出版社, 2003; 513.
16. 骆抗先, 主编. 乙型肝炎－基础和临床. 第1版. 北京: 人民卫生出版社, 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. 谢仕斌, 陈幼明, 谢冬英, 等. 血清透明质酸测定对肝纤维化诊断的临床意义. 中山医科大学学报, 1998; 19(3): 211～213.
22. 简希尧, 郑国安, 廖小辉, 马松炎. 血清纤维化指标与超声联合评价肝纤维化程度的研究. 国药产业资讯, 2006; 3(11): 7～9.
23. 陈永鹏, 冯筱榕, 戴琳, 等. 代偿性肝硬化无创性诊断指标的筛选及评价. 中华肝脏病杂志, 2003; 11(4): 225～227.
24. 张敏, 张玲霞, 赵景民, 等. 慢性病毒性肝炎血清纤维化诊断指标评估. 传染病信息, 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. 血清指标与慢性肝炎病理关系分析. 医学理论与实践, 2001; 14(11): 1093～1094.
29. 陈煜, 段钟平, 王宝恩, 等. 早期肝硬化的血清学诊断临床研究. 临床荟萃, 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. 董红筠, 李颖, 赵桂鸣. 血清肝纤维化指标与肝脏病理学对照观察. 临床消化病杂志, 2006; 18(2): 93～94.
38. 蔡卫民, 张彬彬, 翁红雷, 等. 八项肝纤维化血清标志物比较研究. 中华肝脏病杂志, 2004; 12(4): 219～222.
39. 顾立祥, 江圣勇, 何伟芳, 等. PGA指数和透明质酸在诊断慢性乙肝肝纤维化中的价值. 中国临床医学, 2002; 9(5): 496～498.
40. 郑敏, 蔡卫民, 翁红雷, 等. ROC 曲线评价血清纤维化指标对诊断肝纤维化的价值. 中华传染病杂志, 2002; 20(4): 225～228.
41. 郝菁华, 邹建文, 高鹏. 血清透明质酸、IV型胶原及层连蛋白检测的临床应用研究. 山东医药, 1999; 39(3): 1～2.
42. 张世兰, 杨永平, 陈德永, 等. 血清透明质酸、III型胶原氨基肽、IV型胶原及层粘蛋白与PGA指数对肝纤维化的诊断意义. 中华传染病杂志, 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.

Chinese Journal of Evidence-Based Medicine

The Diagnostic Value of Serum Hyaluronic Acid for Liver Fibrosis in Patients with Chronic Viral Hepatitis: A Systematic Review

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