Introduction Primary bile acid diarrhoea (BAD), also known as idiopathic bile acid malabsorption, is a common cause of chronic functional diarrhoea and irritable bowel syndrome with diarrhoea. BAD has been shown to be associated with fatty liver disease including non-alcoholic steatohepatitis (NASH), with shared mechanisms being reported. In our previous proof-of-concept study, patients with BAD had significant clinical improvements in stool type and frequency when treated for two weeks with the first-in-class farnesoid X receptor (FXR) agonist obeticholic acid (OCA). In a case report using OCA for 6 months, in addition to clinical improvement, normalisation of the diagnostic SeHCAT test was found. The aim of this study was to see if further evidence for benefits of FXR agonists on diarrhoea could be found in the recently published results from the 18-month interim analysis of a large phase 3 study of OCA in NASH (Younossi ZM, et al. Lancet 2019; 394:2184–2196).

Methods The published results of the interim analysis were analysed independently. Patients with NASH fibrosis (n=1968) had been randomly allocated to placebo, OCA 10 mg, or OCA 25 mg daily. Patient-reported adverse reactions had been recorded per protocol. Figures for newly incident events of diarrhoea and constipation were given. The frequencies of these events were compared between the groups.

Results Incidents of diarrhoea were reported in 12% of patients in the placebo-treated group. These were significantly fewer in both OCA-treatment groups, at 7% (p<0.005, Fisher’s exact tests). Incidents of constipation were the opposite, occurring in 5% with placebo treatment, 10% with OCA 10 mg and 11% with OCA 25 mg (p<0.003).

Conclusion Analysis of this trial of OCA in NASH patients indicates that treatment with FXR agonists reduces episodes of diarrhoea and increases constipation. This is presumably by the demonstrated effects of FXR agonists, stimulating FGF19 and reducing bile acid synthesis. Although the primary focus of the trial is on liver fibrosis, these results provide further evidence that FXR agonists can be a therapeutic option in BAD. Trials of FXR agonists in development should include analysis of effects on bowel function, and specifically look at the response in patients with BAD.