PRO‐C3, a Serological Marker of Fibrosis, During Childhood and Correlations With Fibrosis in Pediatric NAFLD

• Published in: Hepatology communications 2021-11, Vol.5 (11), p.1860-1872
• Main Authors: Cohen, Catherine C., Castillo‐Leon, Eduardo, Farris, Alton B., Caltharp, Shelley A., Cleeton, Rebecca L., Sinclair, Elizabeth M., Shevell, Diane E., Karsdal, Morten A., Nielsen, Mette Juul Fisker, Leeming, Diana J., Vos, Miriam B.
• Format: Article
• Language: English
• Subjects: Adolescent; Age Factors; Biomarkers; Biomarkers - blood; Biopsy; Body mass index; Bone Remodeling - genetics; Child; Childhood; Collagen; Collagen Type I - blood; Complement C3 - analysis; Cross-Sectional Studies; Ethnicity; Extracellular matrix; Female; Humans; Inflammation; Laboratories; Liver cirrhosis; Liver Cirrhosis - etiology; Liver Cirrhosis - genetics; Liver diseases; Male; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - genetics; Original; Osteocalcin - blood; Overweight; Pediatrics; Peptides; Peptides - blood; Puberty - blood; Puberty - genetics; Severity of Illness Index
• ISSN: 2471-254X; 2471-254X
• DOI: 10.1002/hep4.1766

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease in children and may lead to cirrhosis requiring liver transplant. Thus, prompt diagnosis of advanced fibrosis is essential. Our objectives were to examine PRO‐C3 (a neo‐epitope pro‐peptide of type III collagen formation) levels across childhood/adolescence and associations with advanced fibrosis in pediatric NAFLD. This cross‐sectional study included 88 children and adolescents with biopsy‐proven NAFLD (mean age: 13.9 ± 2.9 years, 71% male) and 65 healthy participants (11.8 ± 4.5 years, 38% male). PRO‐C3, and the bone remodeling biomarkers C‐terminal telopeptide of type I collagen (CTX‐I; bone resorption) and osteocalcin (N‐MID; bone formation), were measured in serum by enzyme‐linked immunosorbent assay. Fibrosis was assessed by liver biopsy in participants with NAFLD, who were categorized as having advanced (Ishak score ≥ 3) or none/mild fibrosis (Ishak score ≤ 2). Overall, PRO‐C3 was similar in participants with NAFLD (median [interquartile range]: 20.6 [15.8, 25.9] ng/mL) versus healthy participants (19.0 [13.8, 26.0] ng/mL), but was significantly lower in older adolescents ≥ 15 years old (16.4 [13.0, 21.2] ng/mL) compared with children ≤ 10 years old (22.9 [18.1, 28.4] ng/mL; P