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Validation of terminal peptide of procollagen III for the detection and assessment of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease

Authors

  • Sudeep Tanwar,

    Corresponding author
    1. UCL Institute of Liver & Digestive Health, Centre for Hepatology, Division of Medicine, University College London, London, U.K
    • UCL Institute of Liver & Digestive Health, Centre for Hepatology, Division of Medicine, University College London, London, U.K
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  • Paul M. Trembling,

    1. UCL Institute of Liver & Digestive Health, Centre for Hepatology, Division of Medicine, University College London, London, U.K
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  • Indra N. Guha,

    1. National Institute for Health Research Biomedical Research Unit (Gastrointestinal and Liver), Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, U.K
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  • Julie Parkes,

    1. Public Health Sciences and Medical Statistics, University of Southampton, Southampton, U.K.
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  • Philip Kaye,

    1. National Institute for Health Research Biomedical Research Unit (Gastrointestinal and Liver), Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, U.K
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  • Alastair D. Burt,

    1. Institute of Cellular Medicine, Newcastle University, Newcastle, U.K
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  • Stephen D. Ryder,

    1. National Institute for Health Research Biomedical Research Unit (Gastrointestinal and Liver), Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, U.K
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  • Guruprasad P. Aithal,

    1. National Institute for Health Research Biomedical Research Unit (Gastrointestinal and Liver), Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, U.K
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  • Christopher P. Day,

    1. Institute of Cellular Medicine, Newcastle University, Newcastle, U.K
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  • William M. Rosenberg

    1. UCL Institute of Liver & Digestive Health, Centre for Hepatology, Division of Medicine, University College London, London, U.K
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  • Potential conflict of interest: Dr. Guha received grants from Pfizer and Conatus.

Abstract

Liver biopsy is the reference standard for the detection of nonalcoholic steatohepatitis (NASH) within nonalcoholic fatty liver disease (NAFLD). The aim of this study was to identify a biomarker of NASH in patients without significant fibrosis. In all, 172 patients from two centers with biopsy-proven NAFLD were included in this study. Eighty-four patients from a single center were included as a derivation cohort and 88 patients from a second center were included as a validation cohort. Serum samples were tested for candidate markers of fibrosis and inflammation alongside hematological and biochemical markers. Among patients without advanced fibrosis, terminal peptide of procollagen III (PIIINP) was the only marker found to be associated with a histological diagnosis of NASH in both cohorts. PIIINP also correlated with the total NAFLD activity score (NAS) and its constituent components (P < 0.001). Area under receiver operating characteristic curve (AUROC) for PIIINP in discriminating between NASH and simple steatosis (SS) was 0.77-0.82 in patients with F0-2 fibrosis and 0.82-0.84 in patients with F0-3 fibrosis. PIIINP was elevated in patients with advanced fibrosis, the overwhelming majority of whom had NASH. When incorporating patients with all degrees of fibrosis from both cohorts, PIIINP was able to discriminate between patients with SS and those with NASH or advanced fibrosis with AUROC 0.85-0.87. Conclusion: PIIINP discriminates between SS and NASH or advanced fibrosis. The use of a single biomarker in this context will be of clinical utility in detecting the minority of patients with NAFLD who have NASH or advanced fibrosis related to NASH. (HEPATOLOGY 2013)

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