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

Background & Aims: 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). Methods: 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. Results: 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. Conclusions: 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.