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Irritable Bowel Syndrome
Published in Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams, Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
Recent evidence indicates that about 28% of patients with IBS-D may have bile acid diarrhoea (BAD).31 The most common cause of BAD is believed to be overproduction of bile acids, leading to a larger than normal pool of bile acids that saturate the transport capacity for bile acids in the distal ileum and leads to increased spill-over of bile acids to the colon. An increased amount of bile acids in the colon will stimulate electrolyte and water secretion and give rise to diarrhoea. The loss of bile acids can be measured using a radiolabelled synthetic bile acid 75Se-homocholic acid-taurine (SeHCAT). The measured entity with the SeHCAT-test is whole body retention of the tracer after seven days. Retention of <10% indicates significant loss of bile acids to faeces. The exact fraction of tracer that should remain after normal losses of bile acids is somewhat controversial, but >15% is often considered normal. Newer methods for assessment of bile acid diarrhoea include measurements of the serum level of 7α-hydroxy-4-cholesten-3-one, which reflects the rate of bile acid synthesis, and the serum level of the protein-hormone fibroblast growth factor 19 (FGF19), which is secreted by enterocytes of the small bowel for the control of bile acid synthesis in the liver.
Current and emerging pharmacological approaches for treating diarrhea-predominant irritable bowel syndrome
Published in Expert Opinion on Pharmacotherapy, 2020
Akhil Munjal, Bhavtosh Dedania, Brooks D. Cash
An open-label study investigated the potential effects of bile acids on IBS symptomatology. 75Se-labeled homocholic acid-taurine (75SeHCAT) retention, serum levels of 7α-hydroxy-4-cholesten-3-one (7C4), and fibroblast growth factor (FGF) 19 were measured in patients with IBS (n = 141) and control subjects (75SeHCAT n = 29; C4 and FGF19 n = 435). Symptom severity and stool form were also recorded for IBS patients. An 8-week open-label treatment was offered to patients with 75SeHCAT <20% and the effects were monitored using an IBS severity scoring system and adequate relief of symptom assessment. This study found that compared with controls, patients with IBS had lower 75SeHCAT retention values (p = 0.005) and higher 7C4 levels (corrected for cholesterol), but similar FGF19 levels. Patients with 75SeHCAT retention <10% had more frequent stools and accelerated colonic transit. Treatment with colestipol improved IBS symptom severity (220 ± 109 vs. 277 ± 106; p < 0.01) and 15/27 patients with lower 75SeHCAT levels fulfilled the criteria for treatment response (>50% relief of symptoms at week 5–8) [56].
Present and emerging pharmacotherapies for non-alcoholic steatohepatitis in adults
Published in Expert Opinion on Pharmacotherapy, 2019
Yuji Ogawa, Masato Yoneda, Takashi Kobayashi, Yasushi Honda, Takaomi Kessoku, Kento Imajo, Satoru Saito, Atsushi Nakajima
A 12-day phase 1 trial conducted in obese subjects revealed a reduction of the serum LDL cholesterol and a 4- to 5-fold increase in fecal bile acid excretion in the volixibat as compared to the placebo group, irrespective of the dose of volixibat used (5–80 mg) (NCT02287779) [84]. In addition, the serum level of 7α-hydroxy-4-cholesten-3-one (C4), which is a surrogate marker for new bile acid synthesis in the liver, also increased by 4- to 5-fold [84]. At present, a phase 2 RCT of volixibat is ongoing, in which the target number of 266 patients from the United Kingdom, United States, Canada, and Puerto Rico are divided into four treatment groups assigned to receive placebo, or 5, 10, or 20 mg of volixibat for 48 weeks, and liver biopsy is performed before and after treatment. The primary outcome is a reduction of the NAS by ≥2 points without worsening of fibrosis. Volixibat has been designated as a fast-track product by the FDA, and the results of the trial appear promising.