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A Novel Diagnostic Biomarker Panel for Obesity-related Nonalcoholic Steatohepatitis (NASH)

Obesity Surgery volume 18, pages 1430–1437 (2008)Cite this article

Abstract

Background

Within the spectrum of nonalcoholic fatty liver disease (NAFLD), only patients with nonalcoholic steatohepatitis (NASH) show convincing evidence for progression. To date, liver biopsy remains the gold standard for the diagnosis of NASH; however, liver biopsy is expensive and associated with a small risk, emphasizing the urgent need for noninvasive diagnostic biomarkers. Recent findings suggest a role for apoptosis and adipocytokines in the pathogenesis of NASH. The aim of this study was to develop a noninvasive diagnostic biomarker for NASH.

Methods

The study included 101 patients with liver biopsies who were tested with enzyme-linked immunosorbent assay (ELISA)-based assays. Of these, 69 were included in the biomarker development set and 32 were included in the biomarker validation set. Clinical data and serum samples were collected at the time of biopsy. Fasting serum samples were assayed for adiponectin, resistin, insulin, glucose, TNF-alpha, IL-6, IL-8, cytokeratin CK-18 (M65 antigen), and caspase-cleaved CK-18 (M30 antigen).

Results

Data analysis revealed that the levels of M30 antigen (cleaved CK-18) predicted histological NASH with 70% sensitivity and 83.7% specificity and area under the curve (AUC) = 0.711, p < 10−4, whereas the predictive value of the levels of intact CK-18 (M65) was higher (63.6% sensitivity and 89.4% specificity and AUC = 0.814, p < 10−4). Histological NASH could be predicted by a combination of Cleaved CK-18, a product of the subtraction of Cleaved CK-18 level from intact CK-18 level, serum adiponectin, and serum resistin with a sensitivity of 95.45% sensitivity, specificity of 70.21%, and AUC of 0.908 (p < 10−4). Blinded validation of this model confirmed its reliability for separating NASH from simple steatosis.

Conclusions

Four ELISA-based tests were combined to form a simple diagnostic biomarker for NASH.

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Acknowledgments

This study has been supported by the Liver Disease Outcomes Fund of the Center for Liver Diseases at Inova Fairfax Hospital, Inova Health System.

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Authors and Affiliations

  1. Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA, 22042, USA

    Zobair M. Younossi, Clare Nugent, Mariam Afendy, Maria Stepanova, Nila Rafiq & Ancha Baranova

  2. Center for the Study of Genomics in Liver Diseases, Molecular and Microbiology Department, George Mason University, Fairfax, VA, USA

    Zobair M. Younossi, Mohammed Jarrar, Manpreet Randhawa, Vikas Chandhoke & Ancha Baranova

  3. Translational Research Institute, Inova Health System, Falls Church, VA, USA

    Zobair M. Younossi, Mohammed Jarrar, Clare Nugent, Manpreet Randhawa, Mariam Afendy, Maria Stepanova, Nila Rafiq, Vikas Chandhoke & Ancha Baranova

  4. Armed Forces Institutes of Pathology, Washington, DC, USA

    Zachary Goodman

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  1. Zobair M. Younossi
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  2. Mohammed Jarrar
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Correspondence to Zobair M. Younossi.

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Younossi, Z.M., Jarrar, M., Nugent, C. et al. A Novel Diagnostic Biomarker Panel for Obesity-related Nonalcoholic Steatohepatitis (NASH). OBES SURG 18, 1430–1437 (2008). https://doi.org/10.1007/s11695-008-9506-y

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  • DOI: https://doi.org/10.1007/s11695-008-9506-y

Keywords

  • Obesity
  • NASH
  • Biomarkers
  • NASH diagnostics