Measurement of serum 7a-hydroxy-4-cholesten-3-one as a marker of bile acid malabsorption in dogs with chronic diarrhoea: a pilot study

Kent, A. C. C.; Cross, G.; Taylor, D. R.; Sherwood, R. A.; Watson, P. J.

Various methods have been described to diagnose bile acid malabsorption in humans (Vijayvargiya and others 2013) . Until recently, the most commonly utilised was the 75 selenium homotaurocholic acid test (SeHCAT); this uses a synthetic radioactive bile acid, the retention time of which can be measured using a gamma camera (Balzer 1995) . A downstream product of one of the major enzymes in the bile acid synthesis pathway is 7α-hydroxy-4-cholesten-3-one (C4) and, in people, blood concentrations show good correlation with the rate of bile acid synthesis (Galman and others 2003) . Bile acid synthesis is increased in patients with bile acid malabsorption as they have increased faecal bile acid losses and therefore less recycling of bile acids through the process of enterohepatic recirculation (Camilleri and others 2009 ). Multiple studies have now shown good correlation between serum C4 and SeHCAT in the diagnosis of bile acid malabsorption with a sensitivity of 87-90 per cent and specificity of 79-86 per cent compared with SeHCAT (Eusufzai and others 1993 , Brydon and others 1996 , Fan and Sellin 2009 , Johnston and others 2011 , Grutzner and others 2014 . C4 has significant advantages over other methods as it only requires one blood sample, avoids radiation risks and does not require immediate access to expensive equipment. To the authors' knowledge, bile acid malabsorption has not been documented in dogs or cats, nor has SeHCAT been described. However, the authors have anecdotal evidence of a clinical response of patients with refractory chronic enteropathies to the bile acid sequestrant cholestyramine, which is a commonly used drug for this condition in people (Pattni and Walters 2009 ). An improved ability to recognise and diagnose cases of bile acid malabsorption would have significant clinical benefit as these cases may require specific treatments for this condition and may be less likely to respond to conventional therapy. The purpose of this study was to document serum C4 concentration in a group of dogs with chronic diarrhoea and to compare this to a group of clinically healthy control dogs. The authors hypothesised that approximately 10 per cent of dogs with chronic diarrhoea would be affected by bile acid malabsorption, indicated by an elevated serum C4 concentration; this figure was based on the reported prevalence in people with chronic enteropathies (Wedlake and others 2009) . They also hypothesised that dogs with hypocobalaminaemia may be more likely to have elevated serum C4 as cobalamin and bile acids are absorbed in a similar region of the small intestine. Lastly, serum C4 concentration was compared with the canine chronic enteropathy activity index in order to determine whether bile acid malabsorption was related to clinical disease severity.