PIIINP and liver fibrosis severity in children with NAFLD

Research Highlights Diagnostics

Expert opinion

Childhood obesity has become a serious public health problem, further increasing the burden of several chronic diseases including Non-Alcoholic Fatty Liver disease (NAFLD).
Pediatric NAFLD is becoming the leading cause of chronic liver diseases, affecting up to 15% of children/adolescents in western countries.
Because there is an unmet need for non-invasive biomarkers, the reference method to diagnose NAFLD remains liver biopsy, but this technique often requires anesthesia and presents potential risks of morbidity. To circumvent this drawback, non-invasive biomarkers to diagnose NAFLD have been deeply investigated over the past decade.
In this study the authors focused on three different approaches: fibrosis four score (FIB-4), Aspartate aminotransferase to Platelet Ratio Index (APRI), and the N-Terminal propeptide of type III Procollagen (PIIINP).
204 children were enrolled in this study, all with biopsy-proven NAFLD, including some with Non-Alcoholic Steato-Hepatitis (NASH). PIIINP tests, Fib-4 scores, and APRI tests were performed and compared.
The results show that children with NASH had higher plasma PIIINP level FIB-4 and APRI than children without NASH. Even more interestingly, there were much better diagnoses and accuracy for PIIINP levels than FIB-4 and APRI for predicting the liver fibrosis stage.
The publication shows classical statistical tests (Fisher’s exact, Student, Mann-Whitney, Kruskal-Wallis…) as well as AUROC, Confidence interval, optimal cut-off, PPV, and NPV.
Conclusions: Unlike APRI and Fib-4, plasma PIIINP levels are a promising, non-invasive biomarker for diagnosing liver fibrosis stages in the child/adolescent proven NAFLD population.


Background & Aims: We examined the diagnostic performance of plasma N‐terminal
propeptide of type III procollagen (PIIINP) levels, the aspartate aminotransferase to platelet
ratio index (APRI), and Fibrosis‐4 (FIB‐4) scores in 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. Plasma PIIINP levels were measured using a commercially available enzyme‐linked immunosorbent assay kit, and APRI and FIB‐4 scores were calculated using standard methods.
Results: Children with NASH had higher plasma PIIINP levels, APRI, and FIB‐4 scores
compared to those without NASH (all P < .001). However, PIIINP levels had much better diagnostic performance and accuracy than APRI and FIB‐4 scores in 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 each 3.6 ng/mL increase in the PIIINP level, 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 areas under the receiver operating characteristics curve were 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, noninvasive biomarker for diagnosing liver fibrosis stage in children/adolescents with biopsy‐ proven NAFLD.


Liver International. 2019;39:2317-2329 (DOI: 10.1111/liv.14225)

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