Assessment of liver function in dogs using the 13 C-galactose breath test S. Silva a, * , C.A. Wyse b , M.R. Goodfellow a , P.S. Yam c , T. Preston d , K. Papasouliotis a , E.J. Hall a a Division of Companion Animal Studies, Department of Clinical Veterinary Science, University of Bristol, Langford House, Langford, Bristol, BS40 5DU, UK b Department of Anatomy, University of Bristol, Southwell Street, Bristol, BS2 8EJ, UK c Division of Companion Animal Studies, Institute of Comparative Medicine, University of Glasgow, Glasgow, G12 9JJ, UK d Scottish Universities Environmental Research Centre, Kelvin Technology Park, East Kilbride, Glasgow G75 0QF, UK article info Article history: Accepted 23 May 2009 Keywords: Liver function Stable isotope Breath test Dog Galactose abstract The aim of this study was to evaluate the application of the 13 C-galactose breath test ( 13 C-GBT) in assess- ing canine liver function by applying it to a group of healthy dogs, and to a group with clinicopathological evidence of liver dysfunction. Breath samples were collected 30 min before ingestion of 13 C-galactose, and then at regular intervals thereafter for 6 h. The proportion of 13 CO 2 / 12 CO 2 in the breath samples was measured by isotope-ratio mass spectrometry. There was no significant difference in recovery of 13 CO 2 in the diseased group, compared to the healthy controls, but there was considerable inter-subject variation in both groups, possibly due to differences in the rate of gastric emptying, which could preclude detection of alterations in hepatic metabolism of galactose. The results of this study do not support the application of the 13 C-GBT for assessment of canine liver function. Ó 2009 Published by Elsevier Ltd. Introduction Hepatic dysfunction is a commonly encountered problem in small animal practice and it is not infrequent for clinical signs to be mild and non-specific. The ‘gold-standard’ for assessing liver disease in dogs is the histological examination of tissue biopsy samples, but this method is invasive and may be inappropriate for screening or for monitoring disease progression. Radiography and abdominal palpation are only useful in indicating the presence of hepatomegaly, whilst ultrasonography may permit the detection of anatomical abnormalities, but cannot provide information on the functional capacity of the liver. Elevated serum liver enzymes such as aspartate aminotransferase (AST), alanine aminotransfer- ase (ALT), alkaline phosphatase (AP) and gamma glutamyltransfer- ase (GGT) can indicate liver damage, but are not specific to primary hepatocyte damage and cannot be used to assess liver function. Similarly, assessment of serum total proteins, albumin and total bilirubin are of some use in establishing a diagnosis of liver disease, but are insensitive indicators of liver function. The most reliable clinical test of canine hepatobiliary function is probably the measurement of pre- and post-prandial bile acids. However, the specificity of the bile acid stimulation test is affected by cholestasis, resulting in elevation of serum bile acids in the presence of normal hepatocyte function. The assessment of canine liver function using a labelled bile-acid ( 14 C-cholic acid) clearance test was recently described (Bosje et al., 2005), but did not offer any additional clinical information over the measurement of serum post-prandial bile acid concentrations. Assessment of plasma ammonia is a useful indicator of portosystemic shunting, had poor sensitivity in detecting primary hepatocellular disease and re- quired a demanding sample collection procedure (Walker et al., 2001; Gerritzen-Bruning et al., 2006). Other tests of liver function that have been described for use in the dog include the 13 C-aminopyrine blood test (Moeller et al., 2001, 2004, 2006), the galactose elimination test (Bernardini et al., 2005), serum phenylalanine test (Neumann et al., 2007a), L-carnitine test (Neumann et al., 2007b), and the bromosulphtha- lein (BSP) retention test (Flatland et al., 2000). However, these tests are not generally available in veterinary clinical practice, particu- larly since they require intravenous (IV) cannulation and some of the test substrates may be toxic (e.g. BSP). Measurement of plasma protein C was reported to improve differentiation of microvascular dysplasia from portosystemic vascular abnormalities, although the overall sensitivity and specificity of this test in differentiating hepatobiliary disease and portosystemic shunting was lower than that reported for the standard method of measurement of total bile acids (Toulza et al., 2006). There is currently no ideal method avail- able for quantitative assessment of liver function in veterinary clinical practice. In human medicine, the rates of metabolism of various isotope- labelled substrates have been used as quantitative probes of liver enzymatic function (Mion et al., 1999; Suzuki et al., 2001; Armuzzi et al., 2002; Saadeh et al., 2003; Giannini et al., 2005). 13 C is a stable isotope of carbon that may be used to label these substrates, with 1090-0233/$ - see front matter Ó 2009 Published by Elsevier Ltd. doi:10.1016/j.tvjl.2009.05.022 * Corresponding author. Tel.: +44 117 9289447; fax: +44 117 9289628. E-mail addresses: Susana.Silva@bristol.ac.uk, susanasrsilva@hotmail.com (S. Silva). The Veterinary Journal 185 (2010) 152–156 Contents lists available at ScienceDirect The Veterinary Journal journal homepage: www.elsevier.com/locate/tvjl