Association of novel markers of liver disease with neonatal liver disease in premature baboons, Papio sp

• Published in: PloS one Vol. 15; no. 3; p. e0228985
• Main Authors: Keller, Laura M., Eighmy, Stephanie, Li, Cun, Winter, Lauryn, Kerecman, Jay, Goodman, Zachary, Mittal, Naveen, Blanco, Cynthia L.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.03.2020; Public Library of Science (PLoS)
• Subjects: Algorithms; Analysis; Animals; Animals, Newborn; Babies; Baboons; Biology and life sciences; Biomarkers - blood; Biomedical research; Birth; Cesarean section; Collagen; Development and progression; Diagnosis; Disease control; Disease Models, Animal; Diseases; Enzyme-linked immunosorbent assay; Euthanasia; Fatty liver; Female; Fibrosis; Gallbladder diseases; Gestation; Hyaluronic acid; Hyaluronic Acid - blood; Hypertrophy; Kupffer Cells - pathology; Liver; Liver diseases; Liver Diseases - etiology; Liver Diseases - metabolism; Liver Diseases - pathology; Male; Markers; Medical research; Medicine and Health Sciences; Metalloproteinase; Monitoring; Necropsy; Neonates; Newborn babies; Newborn infants; Novels; Nutrition; Papio; Parenteral nutrition; Parenteral Nutrition - adverse effects; Pediatrics; Pregnancy; Premature babies; Premature Birth; Primate Diseases - chemically induced; Primate Diseases - metabolism; Primate Diseases - pathology; Steatosis; Tissue inhibitor of metalloproteinase 1; Tissue Inhibitor of Metalloproteinase-1 - blood; Texas; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0228985

Parenteral Nutrition (PN) Associated Liver Disease (PNALD) affects up to 60% of neonates; however, techniques for diagnosing and monitoring disease progression remain limited. The neonatal baboon model may provide a unique opportunity to identify serologic markers associated with this disease. The purpose of this study was to investigate if Hyaluronic Acid (HA), TIMP metallopeptidase inhibitor 1 (TIMP1), Amino-terminal Propeptide of Type-III Collagen (PIIINP) and Enhanced Liver Fibrosis (ELF) score associate with histological liver disease in neonatal baboons exposed to PN. Preterm baboons delivered via c-section at 67% gestation received PN for 14 days with or without Intralipid (PRT+IL, PRT-IL, respectively) or were sacrificed after birth (PRTCTR). Term baboons were sacrificed after birth (TERMCTR) or survived 14 days (TERM+14d). Serum HA, TIMP1, and PIIINP concentrations were measured by ELISA. A blinded pathologist assigned liver histological scores following necropsy. HA increased 9.1-fold, TIMP1 increased 2.2-fold, and ELF score increased 1.4-fold in PRT-IL compared to PRTCTR. ALT, AST, and GGT were within normal limits and did not vary between groups. A trend towards increased fibrosis was found in PRT-IL baboons. Microvesicular hepatocyte steatosis and Kupffer cell hypertrophy were elevated in PRT-IL vs PRTCTR. HA and TIMP1 were significantly elevated in preterm baboons with early histological findings of liver disease evidenced by hepatic steatosis, Kupffer cell hypertrophy and a trend towards fibrosis whereas traditional markers of liver disease remained normal. These novel markers could potentially be utilized for monitoring early hepatic injury in neonates.