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Type IV collagen 7s domain is an independent clinical marker of the severity of fibrosis in patients with nonalcoholic steatohepatitis before the cirrhotic stage

  • Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

The changes in nonalcoholic fatty liver disease range over a wide spectrum, extending from simple steatosis to nonalcoholic steatohepatitis (NASH). We investigated the clinical usefulness of the type IV collagen 7s domain and hyaluronic acid for predicting the severity of fibrosis before progression to the cirrhotic stage in NASH patients.

Methods

The type IV collagen 7s domain and hyaluronic acid were measured in 72 patients with histologically verified NASH.

Results

In a univariate analysis, marked elevation of hyaluronic acid and the type IV collagen 7s domain was observed in the NASH patients with advanced fibrosis compared with those with mild fibrosis (P = 0.0028, P = 0.0006, respectively). For detection of NASH with advanced fibrosis, the area under the receiver-operating characteristic curves for type IV collagen 7s domain and hyaluronic acid were 0.767 and 0.754, respectively. However, multiple regression analysis revealed that the type IV collagen 7s domain, but not hyaluronic acid, was significantly elevated in patients with advanced fibrosis even after adjustment for age, sex, platelet count, prothrombin time, aspartate aminotransferase/alanine aminotransferase ratio, body mass index, and presence of underlying type 2 diabetes mellitus, all of which have previously been reported as useful predictors of advanced fibrosis in patients with NASH (P = 0.0127, P = 0.2804, respectively).

Conclusions

This is the first report to demonstrate a consistent and profound elevation of the type IV collagen 7s domain in NASH patients with advanced fibrosis (before progression to the stage of cirrhosis) compared with those with mild fibrosis.

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References

  1. P Angulo (2002) ArticleTitleNonalcoholic fatty liver disease N Engl J Med 18 1221–31 Occurrence Handle10.1056/NEJMra011775

    Article  Google Scholar 

  2. GC Farrell (2003) ArticleTitleNon-alcoholic steatohepatitis: what is it, and why is it important in the Asia-Pacific region? J Gastroenterol Hepatol 18 124–38 Occurrence Handle12542595 Occurrence Handle10.1046/j.1440-1746.2003.02989.x

    Article  PubMed  Google Scholar 

  3. AM Diehl Z Goodman KG Ishak (1988) ArticleTitleAlcohollike liver disease in nonalcoholics. A clinical and histologic comparison with alcohol-induced liver injury Gastroenterology 95 1056–62 Occurrence Handle3410220 Occurrence Handle1:STN:280:DyaL1czhtlGjsQ%3D%3D

    PubMed  CAS  Google Scholar 

  4. J Ludwig TR Viggiano DB McGill BJ Oh (1980) ArticleTitleNonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease Mayo Clin Proc 55 434–8 Occurrence Handle7382552 Occurrence Handle1:STN:280:DyaL3c3gvVeqtQ%3D%3D

    PubMed  CAS  Google Scholar 

  5. EM Brunt (2001) ArticleTitleNonalcoholic steatohepatitis: definition and pathology Semin Liver Dis 21 3–16 Occurrence Handle11296695 Occurrence Handle10.1055/s-2001-12925 Occurrence Handle1:STN:280:DC%2BD3MrgsVGrtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  6. JF Cadranel (2002) ArticleTitleGood clinical practice guidelines for fine needle aspiration biopsy of the liver: past, present and future Gastroenterol Clin Biol 26 823–4 Occurrence Handle12434092 Occurrence Handle1:STN:280:DC%2BD38nntlaruw%3D%3D

    PubMed  CAS  Google Scholar 

  7. T Poynard V Ratziu P Bedossa (2000) ArticleTitleAppropriateness of liver biopsy Can J Gastroenterol 14 543–8 Occurrence Handle10888734 Occurrence Handle1:STN:280:DC%2BD3czptlahsQ%3D%3D

    PubMed  CAS  Google Scholar 

  8. P Angulo JC Keach KP Batts KD Lindor (1999) ArticleTitleIndependent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis Hepatology 30 1356–62 Occurrence Handle10573511 Occurrence Handle10.1002/hep.510300604 Occurrence Handle1:STN:280:DC%2BD3c%2Fkt1ejtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  9. V Ratziu P Giral F Charlotte E Bruckert V Thibault I Theodorou et al. (2000) ArticleTitleLiver fibrosis in overweight patients Gastroenterology 118 1117–23 Occurrence Handle10833486 Occurrence Handle10.1016/S0016-5085(00)70364-7 Occurrence Handle1:STN:280:DC%2BD3c3psFSntg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  10. M Shimada E Hashimoto H Kaneda S Noguchi N Hayashi (2002) ArticleTitleNonalcoholic steatohepatitis: risk factors for liver fibrosis Hepatol Res 24 429–38 Occurrence Handle12479942 Occurrence Handle10.1016/S1386-6346(02)00246-2

    Article  PubMed  Google Scholar 

  11. U Lindqvist TC Laurent (1992) ArticleTitleSerum hyaluronan and aminoterminal propeptide of type III procollagen: variation with age Scand J Clin Lab Invest 52 613–21 Occurrence Handle1455153 Occurrence Handle1:STN:280:DyaK3s%2Fosl2ksQ%3D%3D

    PubMed  CAS  Google Scholar 

  12. T Ueno S Inuzuka T Torimura H Oohira H Ko K Obata et al. (1992) ArticleTitleSignificance of serum type-IV collagen levels in various liver diseases. Measurement with a one-step sandwich enzyme immunoassay using monoclonal antibodies with specificity for pepsin-solubilized type-IV collagen Scand J Gastroenterol 27 513–20 Occurrence Handle1631498 Occurrence Handle1:STN:280:DyaK38zjsFyjsA%3D%3D

    PubMed  CAS  Google Scholar 

  13. Y Murawaki Y Ikuta M Koda H Kawasaki (1994) ArticleTitleSerum type III procollagen peptide, type IV collagen 7S domain, central triple-helix of type IV collagen and tissue inhibitor of metalloproteinases in patients with chronic viral liver disease: relationship to liver histology Hepatology 20 780–7 Occurrence Handle7927217 Occurrence Handle10.1002/hep.1840200403 Occurrence Handle1:STN:280:DyaK2M%2Fht1Sqsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  14. T Suou S Yamada K Hosho N Yoshikawa H Kawasaki (1996) ArticleTitleRelationship between serum and hepatic 7S fragments of type IV collagen in chronic liver disease Hepatology 23 1154–8 Occurrence Handle8621148 Occurrence Handle10.1002/hep.510230533 Occurrence Handle1:STN:280:DyaK283gs1GntQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  15. H Sakugawa T Nakayoshi K Kobashigawa T Yamashiro T Maeshiro S Miyagi et al. (2005) ArticleTitleClinical usefulness of biochemical markers of liver fibrosis in patients with nonalcoholic fatty liver disease World J Gastroenterol 11 255–9 Occurrence Handle15633226 Occurrence Handle1:CAS:528:DC%2BD2MXhs1eiur0%3D

    PubMed  CAS  Google Scholar 

  16. DR Matthews JP Hosker AS Rudenski BA Naylor DF Treacher RC Turner (1985) ArticleTitleHomeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man Diabetologia 28 412–9 Occurrence Handle3899825 Occurrence Handle10.1007/BF00280883 Occurrence Handle1:CAS:528:DyaL2MXlslKnu7k%3D

    Article  PubMed  CAS  Google Scholar 

  17. JC Levy DR Matthews MP Hermans (1998) ArticleTitleCorrect homeostasis model assessment (HOMA) evaluation uses the computer program Diabetes Care 21 2191–2 Occurrence Handle9839117 Occurrence Handle10.2337/diacare.21.12.2191 Occurrence Handle1:STN:280:DyaK1M%2Fls1CqtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  18. T Ono N Shiga Y Taneda S Umemura (1999) ArticleTitleThe fasting-plasma glucose range in which insulin resistance measured by homeostasis model assessment correlates with euglycemic clamping J Jpn Diabetes Soc 42 1005–11

    Google Scholar 

  19. T Yoshizumi T Nakamura M Yamane AH Islam M Menju K Yamasaki et al. (1999) ArticleTitleAbdominal fat: standardized technique for measurement at CT Radiology 211 283–6 Occurrence Handle10189485 Occurrence Handle1:STN:280:DyaK1M3gsFCrsQ%3D%3D

    PubMed  CAS  Google Scholar 

  20. MR Teli OF James AD Burt MK Bennett CP Day (1995) ArticleTitleThe natural history of nonalcoholic fatty liver: a follow-up study Hepatology 22 1714–9 Occurrence Handle7489979 Occurrence Handle1:STN:280:DyaK28%2FovVyhtQ%3D%3D Occurrence Handle10.1002/hep.1840220616

    Article  PubMed  CAS  Google Scholar 

  21. CA Matteoni ZM Younossi T Gramlich N Boparai YC Liu AJ McCullough (1999) ArticleTitleNonalcoholic fatty liver disease: a spectrum of clinical and pathological severity Gastroenterology 116 1413–9 Occurrence Handle10348825 Occurrence Handle10.1016/S0016-5085(99)70506-8 Occurrence Handle1:STN:280:DyaK1M3nvVamtw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  22. JM Hui JG Kench S Chitturi A Sud GC Farrell K Byth et al. (2003) ArticleTitleLong-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C Hepatology 38 420–7 Occurrence Handle12883486 Occurrence Handle10.1053/jhep.2003.50320

    Article  PubMed  Google Scholar 

  23. AJ Sanyal (2002) ArticleTitleTreatment of non-alcoholic fatty liver disease J Gastroenterol Hepatol 17 IssueIDSuppl 3 S385–8 Occurrence Handle12472968 Occurrence Handle10.1046/j.1440-1746.17.s3.32.x

    Article  PubMed  Google Scholar 

  24. J Choudhury AJ Sanyal (2004) ArticleTitleClinical aspects of fatty liver disease Semin Liver Dis 24 349–62 Occurrence Handle15605303 Occurrence Handle10.1055/s-2004-860864

    Article  PubMed  Google Scholar 

  25. AJ Sanyal (2002) ArticleTitleAGA technical review on nonalcoholic fatty liver disease Gastroenterology 123 1705–25 Occurrence Handle12404245 Occurrence Handle10.1053/gast.2002.36572

    Article  PubMed  Google Scholar 

  26. AE Reid (2001) ArticleTitleNonalcoholic steatohepatitis Gastroenterology 121 710–23 Occurrence Handle11522755 Occurrence Handle10.1053/gast.2001.27126 Occurrence Handle1:STN:280:DC%2BD3MvnvFSltg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  27. S Saadeh ZM Younossi EM Remer T Gramlich JP Ong M Hurley et al. (2002) ArticleTitleThe utility of radiological imaging in nonalcoholic fatty liver disease Gastroenterology 123 745–50 Occurrence Handle12198701 Occurrence Handle10.1053/gast.2002.35354

    Article  PubMed  Google Scholar 

  28. J Guechot RE Poupon P Giral B Balkau J Giboudeau R Poupon (1994) ArticleTitleRelationship between procollagen III aminoterminal propeptide and hyaluronan serum levels and histological fibrosis in primary biliary cirrhosis and chronic viral hepatitis C J Hepatol 20 388–93 Occurrence Handle8014451 Occurrence Handle10.1016/S0168-8278(94)80013-8 Occurrence Handle1:CAS:528:DyaK2cXktVKntLY%3D

    Article  PubMed  CAS  Google Scholar 

  29. S Takamatsu H Nakabayashi Y Okamoto H Nakano (1997) ArticleTitleNoninvasive determination of liver collagen content in chronic hepatitis. Multivariate regression modeling with blood chemical parameters as variables J Gastroenterol 32 355–60 Occurrence Handle9213250 Occurrence Handle1:STN:280:DyaK2szls1yitg%3D%3D Occurrence Handle10.1007/BF02934493

    Article  PubMed  CAS  Google Scholar 

  30. CT Wai JK Greenson RJ Fontana JD Kalbfleisch JA Marrero HS Conjeevaram et al. (2003) ArticleTitleA simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C Hepatology 38 518–26 Occurrence Handle12883497 Occurrence Handle10.1053/jhep.2003.50346

    Article  PubMed  Google Scholar 

  31. PR Gibson JR Fraser TJ Brown CF Finch PA Jones JC Colman et al. (1992) ArticleTitleHemodynamic and liver function predictors of serum hyaluronan in alcoholic liver disease Hepatology 15 1054–9 Occurrence Handle1592343 Occurrence Handle10.1002/hep.1840150614 Occurrence Handle1:STN:280:DyaK383nsFGgug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  32. RE Poupon B Balkau J Guechot F Heintzmann (1994) ArticleTitlePredictive factors in ursodeoxycholic acid-treated patients with primary biliary cirrhosis: role of serum markers of connective tissue Hepatology 19 635–40 Occurrence Handle8119688 Occurrence Handle10.1002/hep.1840190314 Occurrence Handle1:STN:280:DyaK2c7msVKntw%3D%3D

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Gastroenterology, Yokohama City University Hospital, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan

    Masato Yoneda, Hironori Mawatari, Koji Fujita, Kyoko Yonemitsu, Shingo Kato, Hirokazu Takahashi, Hiroyuki Kirikoshi, Masahiko Inamori, Yuichi Nozaki, Yasunobu Abe, Kensuke Kubota, Satoru Saito & Atsushi Nakajima

  2. Division of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Tomoyuki Iwasaki & Yasuo Terauchi

  3. Division of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Shinji Togo

  4. Kitakashiwa Rehabilitation Hospital, Kashiwa, Japan

    Shiro Maeyama

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  1. Masato Yoneda
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Yoneda, M., Mawatari, H., Fujita, K. et al. Type IV collagen 7s domain is an independent clinical marker of the severity of fibrosis in patients with nonalcoholic steatohepatitis before the cirrhotic stage. J Gastroenterol 42, 375–381 (2007). https://doi.org/10.1007/s00535-007-2014-3

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  • DOI: https://doi.org/10.1007/s00535-007-2014-3

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