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.

Control dogs had a serum C4 range from 15.1 to 180.1 nmol/l (median 80.9 nmol/l), dogs with chronic diarrhoea had a serum C4 range from 21.3 to 518.6 nmol/l (median 59.9 nmol/l) and there was no significant difference in the C4 concentration between these two groups (P=0.8). Figure 1 shows a boxplot of the serum C4 concentration in the two groups. Serum cobalamin and canine chronic enteropathy activity index were available for all clinical cases. Cobalamin concentration ranged from 100 to 834 pg/ml (median 338 pg/ml), and canine chronic enteropathy activity index scores ranged from 4 to 15 (median 7). When assessing the relationship between serum C4 concentration and serum cobalamin, no statistically significant relationship was identified (P=0.6, correlation coefficient=−0.11). There was also no statistically significant relationship between canine chronic enteropathy activity index and serum C4 (P=0.6, correlation coeffi-cient=−0.04). A cut-off value for serum C4 concentration of 187.2 nmol/l on the ROC curve resulted in a specificity of 100 per cent (95 per cent CI 81.5 to 100 per cent) and a sensitivity of 25 per cent (95 per cent CI 5.3 to 48.6 per cent) for presumptive diagnosis of bile acid malabsorption in this group of dogs (Fig 2) , with a positive predictive value (PPV) of 100 per cent (95 per cent CI 31 to 100 per cent) and a negative predictive value (NPV) of 59 per cent (95 per cent CI 41 to 75 per cent). If 187.2 nmol/l is set as the upper limit of normal, then three (17.6 per cent; 95 per cent CI 6.2 to 41.0 per cent) of the clinical cases with chronic diarrhoea had a serum C4 concentration significantly above this (at least twice this upper limit). The greatest serum C4 concentration (518.6 nmol/l) was observed in an 11-year-old, neutered male border terrier. This dog was diagnosed with suspected inflammatory bowel disease, which was partially, although never fully, responsive to dietary modification and immunosuppressive medication ( prednisolone and azathioprine). This dog had a serum cobalamin concentration within the reference range (550 pg/ml). The second case with a marked serum C4 elevation (438.0 nmol/l) was a 6-year-old, neutered male border collie. This dog had a complex medical history of previous primary hypoparathyroidism and more recent inflammatory bowel disease. Concerns regarding the effect of prednisolone on serum calcium concentrations prevented use of this drug, and so the dog was primarily managed with chlorambucil and dietary modification; however, his diarrhoea was also poorly responsive to this treatment. Interestingly, at a later time this case was trialled on cholestyramine and showed an improvement in faecal consistency; however, a further dietary modification was made at the same time, making the response difficult to interpret. This dog also had significant hypocobalaminaemia (100 pg/ml), suggesting marked distal small intestinal disease. The third case (serum C4 concentration 362.7 nmol/l) was a 5-year-old, neutered female Jack Russell terrier cross. This dog presented for investigation of chronic diarrhoea and panhypoproteinaemia and was diagnosed with idiopathic inflammatory bowel disease. She was treated with prednisolone, chlorambucil and metronidazole, along with dietary modification. This resulted in an improvement of clinical signs and normalisation of serum proteins; however, the diarrhoea persisted intermittently. Malabsorption of bile acids may offer a potential explanation for th