Post-cholecystectomy diarrhoea: New light on old problem

Up to 10% of patients who have had cholecystectomies suffer from symptomatic diarrhoea. The mechanism of this diarrhoea is not fully understood. It is often assumed that the diarrhoea is caused by increased bile acid. The evidence for this is based on studies which show that twothirds of patients who experience diarrhoea after the operation have excess bile acid and respond to cholestyramine, a bile acid sequestrant.1 Other poorly understood neuroendocrine effects of cholecystectomy may also be contributory factor and may account for the remaining third of patients. The mechanism by which there is increased bile acid in the lower gut after cholecystectomy is unclear. There are several proposals: a faster enterohepatic recycling of bile acids with increased bile acid synthesis or a change in the composition of the bile acid pool could play a role. The bile synthesis rate may be assessed with plasma 7αhydroxy4cholesten3one (C4), whereas ileal reabsorption of bile acids may be assessed with plasma fibroblast growth factor 19 (FGF19).2 In patients with bile acid diarrhoea, lower fasting FGF19 and higher fasting C4 have been previously demonstrated. In this paper, Borup et al tries to shed more light into this intriguing condition.3 They measured FGF19 and C4 levels in 18 individuals before and after cholecystectomy. FGF19 is stimulated in the ileum in response to bile acid and is thus a useful biomarker for ileal bile acid load. They assessed their symptoms and looked at fasting and postprandial levels of FGF19 in these individuals before and after cholecystectomy. They demonstrated that fasting levels of FGF19 are unchanged but postprandial levels are significantly increased after cholecystectomy. They also found that fasting C4 levels to be unchanged after cholecystectomy in their cohort. These results are puzzling and could lead to a rethink as to the mechanism of postcholecystectomy diarrhoea. Unfortunately, none of the patients they studied had symptomatic diarrhoea. This is likely to be a statistical fluke and rather unfortunate as these results suggest that both bile acid production and recycling is increased after cholecystectomy. Perhaps if they could continue their studies and recruit a larger cohort they may start to further elucidate the pathophysiology of postcholecystectomy diarrhoea.