Association of novel markers of liver disease with neonatal liver disease in premature baboons, Papio sp.
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 p...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0228985 |
| _version_ | 1818743254221324288 |
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| author | Laura M Keller Stephanie Eighmy Cun Li Lauryn Winter Jay Kerecman Zachary Goodman Naveen Mittal Cynthia L Blanco |
| author_facet | Laura M Keller Stephanie Eighmy Cun Li Lauryn Winter Jay Kerecman Zachary Goodman Naveen Mittal Cynthia L Blanco |
| author_sort | Laura M Keller |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T02:25:29Z |
| format | Article |
| id | doaj.art-7c8d8785f1024857ba65e9323b7caf06 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-18T02:25:29Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7c8d8785f1024857ba65e9323b7caf062022-12-21T21:24:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01153e022898510.1371/journal.pone.0228985Association of novel markers of liver disease with neonatal liver disease in premature baboons, Papio sp.Laura M KellerStephanie EighmyCun LiLauryn WinterJay KerecmanZachary GoodmanNaveen MittalCynthia L BlancoParenteral 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.https://doi.org/10.1371/journal.pone.0228985 |
| spellingShingle | Laura M Keller Stephanie Eighmy Cun Li Lauryn Winter Jay Kerecman Zachary Goodman Naveen Mittal Cynthia L Blanco Association of novel markers of liver disease with neonatal liver disease in premature baboons, Papio sp. PLoS ONE |
| title | Association of novel markers of liver disease with neonatal liver disease in premature baboons, Papio sp. |
| title_full | Association of novel markers of liver disease with neonatal liver disease in premature baboons, Papio sp. |
| title_fullStr | Association of novel markers of liver disease with neonatal liver disease in premature baboons, Papio sp. |
| title_full_unstemmed | Association of novel markers of liver disease with neonatal liver disease in premature baboons, Papio sp. |
| title_short | Association of novel markers of liver disease with neonatal liver disease in premature baboons, Papio sp. |
| title_sort | association of novel markers of liver disease with neonatal liver disease in premature baboons papio sp |
| url | https://doi.org/10.1371/journal.pone.0228985 |
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