title: Markers of hepatic regeneration associated with surgical attenuation of congenital portosystemic shunts in dogs.
abstract: Dogs with congenital portosystemic shunts (CPSS) have liver hypoplasia and hepatic insufficiency. Surgical CPSS attenuation results in liver growth associated with clinical improvement. The mechanism of this hepatic response is unknown, although liver regeneration is suspected. This study investigated whether markers of liver regeneration were associated with CPSS attenuation. Dogs treated with CPSS attenuation were prospectively recruited. Residual liver tissue was collected for gene expression analysis (seven genes) from 24 CPSS dogs that tolerated complete attenuation, 25 dogs that tolerated partial attenuation and seven control dogs. Relative gene expression was measured using quantitative polymerase chain reaction (qPCR). Blood samples were collected before, 24 h and 48 h post-surgery from 36 CPSS dogs and from 10 control dogs. Serum hepatocyte growth factor (HGF) concentration was measured using a canine specific enzyme-linked immunosorbent assay (ELISA). HGF mRNA expression was significantly decreased in CPSS compared with control dogs (P = 0.046). There were significant increases in HGF (P = 0.050) and methionine adenosyltransferase 2 A (MAT2A; P = 0.002) mRNA expression following partial CPSS attenuation. Dogs with complete attenuation had significantly greater MAT2A (P = 0.024) mRNA expression compared with dogs with partial attenuation. Serum HGF concentration significantly increased 24 h following CPSS attenuation (P < 0.001). Hepatic mRNA expression of two markers of hepatocyte proliferation (HGF and MAT2A) was associated with the response to surgery in dogs with CPSS, and serum HGF significantly increased following surgery, suggesting hepatocyte proliferation. These findings support the concept that hepatic regeneration is important in the hepatic response to CPSS surgery.
authors.affiliation: Department of Veterinary Clinical Sciences, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, AL9 7TA, United Kingdom; Cave Veterinary Specialists, George's Farm, West Buckland, Nr. Wellington, TA21 9LE, United Kingdom. Electronic address: mtivers@cave-vet-specialists.co.uk.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Tivers
authors.affiliation: Department of Veterinary Clinical Sciences, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, AL9 7TA, United Kingdom.
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Lipscomb
authors.affiliation: Department of Pathology and Infectious Diseases, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, AL9 7TA, United Kingdom.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Smith
authors.affiliation: Department of Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London, NW1 0TU, United Kingdom.
authors.forename: Caroline P D
authors.initials: CP
authors.lastname: Wheeler-Jones
authors.affiliation: Veterinary Referral Hospital, 18/151-159 Princess Hwy, Hallam, Vic, Australia.
authors.forename: Arthur K
authors.initials: AK
authors.lastname: House
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D004283:Dog Diseases / Q000151:congenital* / Q000378:metabolism / Q000601:surgery; D004285:Dogs; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000235:genetics*; D008099:Liver / Q000002:abnormalities / Q000254:growth & development / Q000502:physiology* / Q000601:surgery*; D011168:Portal System / Q000002:abnormalities / Q000601:surgery*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor
keywords: Biomarker; Dog; Liver; Portosystemic shunt; Regeneration