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A simple scoring system using type IV collagen 7S and aspartate aminotransferase for diagnosing nonalcoholic steatohepatitis and related fibrosis

  • Original Article―Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Recently we reported novel noninvasive scoring systems for diagnosing nonalcoholic steatohepatitis (NASH) and related fibrosis, namely FM-NASH index and FM-fibro index. They are highly accurate, however, they contain some items not widely used in clinical practice and require six or more items to diagnose both NASH and related fibrosis. By focusing on widely used items, we tried to identify convenient markers in common with the both diagnoses.

Methods

To explore the markers for NASH and related fibrosis in nonalcoholic fatty liver disease (NAFLD) patients, we used data of 24 clinical items in our previous report. By logistic regression analysis, we identified items suitable for the both diagnoses. We then evaluated their accuracies by area under the receiver operator characteristic curves (AUROCs) on independent validation data.

Results

We identified the combination of type IV collagen 7S and aspartate aminotransferase (AST) as the predictor both for NASH and related fibrosis. We developed a scoring system based on the combination and evaluated the prediction accuracy: the AUROCs for training/validation data sets are 0.857/0.769 for NASH and 0.918/0.842 for NASH-related fibrosis. The former was higher than that of NAFIC score, and the latter was higher than those of existing fibrosis markers: BARD score, FIB-4 index and NAFLD fibrosis score but lower than FM-fibro index.

Conclusions

The scoring system using type IV collagen 7S and AST named CA index can predict both NASH and related fibrosis in NAFLD patients with sufficient accuracy and could be a convenient diagnostic and screening tool for NASH and related fibrosis. The scoring system needs to be validated in independent larger populations from multiple clinical centers.

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Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

AUROC:

Area under the receiver operator characteristic curve

BMI:

Body mass index

cfNRI:

Category-free net reclassification improvement

GGT:

Gamma-glutamyl transferase

HA:

Hyaluronic acid

IDI:

Integrated discrimination improvement

NAFL:

Nonalcoholic fatty liver

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

ROC:

Receiver operator characteristic curve

VCAM1:

Vascular cell adhesion molecule 1

References

  1. Weiß J, Rau M, Geier A. Non-alcoholic fatty liver disease: epidemiology, clinical course, investigation, and treatment. Dtsch. Ärzteblatt Int. 2014;111:447–52.

    Google Scholar 

  2. Sayiner M, Koenig A, Henry L, et al. Epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in the United States and the rest of the world. Clin Liver Dis. 2016;20:205–14.

    Article  PubMed  Google Scholar 

  3. Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149(389–397):e10.

    Google Scholar 

  4. Matteoni CA, Younossi ZM, Gramlich T, et al. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116:1413–9.

    Article  CAS  PubMed  Google Scholar 

  5. Sumida Y, Nakajima A, Itoh Y. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2014;20:475–85.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Fitzpatrick E, Dhawan A. Noninvasive biomarkers in non-alcoholic fatty liver disease: current status and a glimpse of the future. World J Gastroenterol. 2014;20:10851–63.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bedossa P, Patel K. Biopsy and noninvasive methods to assess progression of nonalcoholic fatty liver disease. Gastroenterology. 2016;150:1811–22.

    Article  PubMed  Google Scholar 

  8. Yoshimura K, Okanoue T, Ebise H, et al. Identification of novel noninvasive markers for diagnosing nonalcoholic steatohepatitis and related fibrosis by data mining. Hepatology. 2016;63:462–73.

    Article  CAS  PubMed  Google Scholar 

  9. Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–21.

    Article  PubMed  Google Scholar 

  10. Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143:29–36.

    Article  CAS  PubMed  Google Scholar 

  11. Pencina MJ, D’Agostino RB, D’Agostino RB, et al. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27:157–72.

    Article  PubMed  Google Scholar 

  12. Pencina MJ, D’Agostino RB, Steyerberg EW. Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med. 2011;30:11–21.

    Article  PubMed  Google Scholar 

  13. Pickering JW, Endre ZH. New metrics for assessing diagnostic potential of candidate biomarkers. Clin J Am Soc Nephrol. 2012;7:1355–64.

    Article  PubMed  Google Scholar 

  14. Sumida Y, Kanemasa K, Douhara A, et al. A proposal of simple scoring system to differentiate nonalcoholic steatohepatitis from nonalcoholic fatty liver disease: we originally named NAFIC score composed of serum ferritin, fasting insulin, type IV collagen 7S. Kanzo. 2008;49:279–81.

    Article  Google Scholar 

  15. Sumida Y, Yoneda M, Hyogo H, et al. A simple clinical scoring system using ferritin, fasting insulin, and type IV collagen 7S for predicting steatohepatitis in nonalcoholic fatty liver disease. J Gastroenterol. 2011;46:257–68.

    Article  CAS  PubMed  Google Scholar 

  16. Harrison SA, Oliver D, Arnold HL, et al. Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease. Gut. 2008;57:1441–7.

    Article  CAS  PubMed  Google Scholar 

  17. Fujii H, Enomoto M, Fukushima W, et al. Applicability of BARD score to Japanese patients with NAFLD. Gut. 2009;58:1566–7.

    Article  CAS  PubMed  Google Scholar 

  18. Raszeja-Wyszomirska J, Szymanik B, Ławniczak M, et al. Validation of the BARD scoring system in Polish patients with nonalcoholic fatty liver disease (NAFLD). BMC Gastroenterol. 2010;10:67.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ruffillo G, Fassio E, Alvarez E, et al. Comparison of NAFLD fibrosis score and BARD score in predicting fibrosis in nonalcoholic fatty liver disease. J Hepatol. 2011;54:160–3.

    Article  PubMed  Google Scholar 

  20. Shah AG, Lydecker A, Murray K, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7:1104–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sumida Y, Yoneda M, Hyogo H, et al. Validation of the FIB4 index in a Japanese nonalcoholic fatty liver disease population. BMC Gastroenterol. 2012;12:2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45:846–54.

    Article  CAS  PubMed  Google Scholar 

  23. Qureshi K, Clements RH, Abrams GA. The utility of the “NAFLD fibrosis score” in morbidly obese subjects with NAFLD. Obes Surg. 2008;18:264–70.

    Article  PubMed  Google Scholar 

  24. Wong VWS, Wong GLH, Chim AML, et al. Validation of the NAFLD fibrosis score in a Chinese population with low prevalence of advanced fibrosis. Am J Gastroenterol. 2008;103:1682–8.

    Article  PubMed  Google Scholar 

  25. Risteli J, Bächinger HP, Engel J, et al. 7-S collagen: characterization of an unusual basement membrane structure. Eur J Biochem. 1980;108:239–50.

    Article  CAS  PubMed  Google Scholar 

  26. Fukutomi T, Sakamoto S, Isobe H, et al. Clinical significance of the serum levels of the 7S domain of type IV collagen in patients with primary biliary cirrhosis. J Gastroenterol Hepatol. 1992;7:596–601.

    Article  CAS  PubMed  Google Scholar 

  27. Matsuzaki Y, Yoshiga S, Sugitani T, et al. Enzyme immunoassay of serum type IV collagen in anti-HCV positive chronic liver diseases. Clin Chim Acta. 1993;221:209–17.

    Article  CAS  PubMed  Google Scholar 

  28. Tsutsumi M, Takase S, Urashima S, et al. Serum markers for hepatic fibrosis in alcoholic liver disease: which is the best marker, Type III procollagen, type IV collagen, laminin, tissue inhibitor of metalloproteinase, or prolyl hydroxylase? Alcohol Clin Exp Res. 1996;20:1512–7.

    Article  CAS  PubMed  Google Scholar 

  29. Sakugawa H, Nakayoshi T, Kobashigawa K, et al. Clinical usefulness of biochemical markers of liver fibrosis in patients with nonalcoholic fatty liver disease. World J Gastroenterol. 2005;11:255–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Shimada M, Kawahara H, Ozaki K, et al. Usefulness of a combined evaluation of the serum adiponectin level, HOMA-IR, and serum type IV collagen 7S level to predict the early stage of nonalcoholic steatohepatitis. Am J Gastroenterol. 2007;102:1931–8.

    Article  CAS  PubMed  Google Scholar 

  31. 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. 2007;42:375–81.

    Article  CAS  PubMed  Google Scholar 

  32. Mizuno M, Shima T, Oya H, et al. Classification of patients with nonalcoholic fatty liver disease using rapid immunoassay of serum type IV collagen compared with that using liver histology and other fibrosis markers. Hepatol. Res. 2016;47:1–10.

    Google Scholar 

  33. Prieto J, Barry M, Sherlock S. Serum ferritin in patients with iron overload and with acute and chronic liver diseases. Gastroenterology. 1975;68:525–33.

    CAS  PubMed  Google Scholar 

  34. Watanabe S, Hashimoto E, Ikejima K, et al. Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. J Gastroenterol. 2015;50:364–77.

    Article  PubMed  Google Scholar 

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Author notes

  1. Takeshi Okanoue, Hayao Ebise and Toshihiro Kai have contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, 1-2 Kawazonocho, Suita, Osaka, 564-0013, Japan

    Takeshi Okanoue, Masayuki Mizuno & Toshihide Shima

  2. Genomic Science Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 3-1-98 Kasugadenaka, Konohana-ku, Osaka, 554-0022, Japan

    Hayao Ebise, Toshihiro Kai & Mikio Aoki

  3. Drug Development Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 3-1-98 Kasugadenaka, Konohana-ku, Osaka, 554-0022, Japan

    Junji Ichihara

Authors
  1. Takeshi Okanoue
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  2. Hayao Ebise
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  3. Toshihiro Kai
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  4. Masayuki Mizuno
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Correspondence to Takeshi Okanoue.

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Okanoue, T., Ebise, H., Kai, T. et al. A simple scoring system using type IV collagen 7S and aspartate aminotransferase for diagnosing nonalcoholic steatohepatitis and related fibrosis. J Gastroenterol 53, 129–139 (2018). https://doi.org/10.1007/s00535-017-1355-9

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  • DOI: https://doi.org/10.1007/s00535-017-1355-9

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