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Plasma N-terminal propeptide of type III procollagen accurately predicts liver fibrosis severity in children with non-alcoholic fatty liver disease.

  • Mosca, Antonella1
  • Comparcola, Donatella2
  • Romito, Ilaria3
  • Mantovani, Alessandro4
  • Nobili, Valerio1, 5
  • Byrne, Christopher D6, 7
  • Alisi, Anna3
  • Targher, Giovanni4
  • 1 Hepatology Gastroenterology and Nutrition, Bambino Gesù Children's Hospital, Rome, Italy. , (Italy)
  • 2 Hepato-Metabolic Disease Unit, IRCCS, Bambino Gesù Children's Hospital, Rome, Italy. , (Italy)
  • 3 Research Unit of Molecular Genetics of Complex Phenotypes, IRCCS, Bambino Gesù Children's Hospital, Rome, Italy. , (Italy)
  • 4 Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy. , (Italy)
  • 5 Department of Pediatrics, University La Sapienza, Rome, Italy. , (Italy)
  • 6 Southampton National Institute for Health Research Biomedical Research Centre, Southampton General Hospital, University Hospital Southampton, Southampton, UK.
  • 7 Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK.
Published Article
Liver international : official journal of the International Association for the Study of the Liver
Publication Date
Dec 01, 2019
DOI: 10.1111/liv.14225
PMID: 31436362


We examined the diagnostic performance of plasma N-terminal propeptide of type III procollagen (PIIINP) levels, aspartate aminotransferase to platelet ratio index (APRI) and Fibrosis-4 (FIB-4) score for predicting non-alcoholic steatohepatitis (NASH) and liver fibrosis stage in children/adolescents with non-alcoholic fatty liver disease (NAFLD). We enrolled 204 children/adolescents with biopsy-proven NAFLD at the "Bambino Gesù" Children's Hospital. We measured plasma PIIINP levels using a commercially available enzyme-linked immunosorbent assay kit and calculated APRI and FIB-4 scores using standard methods. Children with NASH had higher plasma PIIINP levels, APRI and FIB-4 scores compared with those without NASH (all P < .001). However, PIIINP levels had much better diagnostic performance and accuracy than APRI and FIB-4 scores for predicting liver fibrosis stage. PIIINP levels correlated with the total NAFLD activity score (NAS) and its constituent components (P < .0001). The risk of either NASH or F ≥ 2 fibrosis progressively increased with increasing PIIINP levels (P < .0001), independent of age, gender, adiposity measures, insulin resistance, NAS score and the patatin-like phospholipase domain-containing protein-3 rs738409 polymorphism. For every 3.6 ng/mL increase in PIIINP levels, the likelihood of having F ≥ 2 fibrosis increased by ~14-fold (adjusted-odds ratio 14.1, 95% CI 5.50-35.8, P < .0001) after adjustment for the aforementioned risk factors. The area under the receiver operating characteristics curve was 0.921 (95% CI 0.87-0.97) for F ≥ 2 fibrosis, and 0.993 (95% CI 0.98-1.0) for F3 fibrosis respectively. Unlike APRI and FIB-4 scores, plasma PIIINP levels are a promising, non-invasive biomarker for diagnosing liver fibrosis stage in children/adolescents with biopsy-proven NAFLD. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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