3 Clinical need and practice
3.1 The aim of this evaluation is to determine the clinical and cost effectiveness of SeHCAT in diagnosing bile acid malabsorption in people with chronic diarrhoea who have been diagnosed with IBS-D and people with Crohn's disease without ileal resection.
3.2 The target condition for this assessment is chronic diarrhoea due to bile acid malabsorption. Diarrhoea is defined as the abnormal passage of loose or liquid stools more than 3 times daily or a volume of stool greater than 200 g/day. Diarrhoea is considered to be chronic if it persists for more than 4 weeks.
3.3 Chronic diarrhoea is one of the most common reasons for referral to a gastrointestinal clinic and can account for as many as 1 in 20 referrals. Estimates of the prevalence of chronic diarrhoea in western populations are between 4% and 5%. The cause of chronic diarrhoea in adults is difficult to ascertain, and people may have several investigations without a definitive cause being identified.
3.4 Bile acid malabsorption is one of several causes of chronic diarrhoea. Bile acids are synthesised in the liver from cholesterol before being transferred in conjugated form to the bile ducts, where they accumulate and are stored in the gall bladder. After a meal, the gall bladder contracts and bile acids flow into the intestinal lumen. Most of the bile acids are then reabsorbed by the distal ileum into the portal circulation and returned to the liver. The bile acids are later secreted into the bile again as part of a recycling process called enterohepatic circulation. Although a small proportion of bile acids (3%) are excreted in the faeces, about 97% of bile acids are recycled.
3.5 In people with bile acid malabsorption, excess bile in the colon stimulates electrolyte and water secretion, which results in chronic watery diarrhoea. Bile acid malabsorption causes diarrhoea by one or more of the following mechanisms:
inducing secretion of sodium and water
increasing colonic motility
inducing mucus secretion
damaging the mucosa, thereby increasing mucosal permeability.
3.6 Bile acid malabsorption has been divided into 3 types depending on aetiology:
type 1: following ileal resection, disease or bypass of the terminal ileum
type 2: primary idiopathic malabsorption
type 3: associated with cholecystectomy, peptic ulcer surgery, chronic pancreatitis, coeliac disease or diabetes mellitus.
3.7 Type 2 bile acid malabsorption has no known cause. In people with type 2 bile acid malabsorption, there is a history of diarrhoea that can be either continuous or intermittent.
3.8 Although not life threatening, bile acid malabsorption can have a considerable impact on lifestyle and quality of life because the associated increased frequency of bowel motions often limits the person's ability to travel or leave the house.
3.9 This evaluation included 2 populations associated with bile acid malabsorption:
people with chronic diarrhoea considered likely to have IBS-D
people with chronic diarrhoea who have been diagnosed with Crohn's disease and have not had an ileal resection.
3.10 Several other populations with chronic diarrhoea were considered but excluded from this evaluation, for example, people with an ileal resection, cholecystectomy or radiation-induced bowel damage.
3.11 IBS is one of the most common functional gastrointestinal disorders. It is a chronic, relapsing and often life-long disorder, characterised by abdominal pain or discomfort associated with defecation, disordered defecation (constipation or diarrhoea, or both), and the sensation of abdominal distension. It can include associated non-colonic symptoms such as lack of sleep, backache, urinary frequency, anxiety and lethargy. Consequences of IBS include time taken off work, avoidance of stressful or social situations, and substantial reduction in quality of life.
3.12 IBS most commonly presents for the first time between the ages of 20 and 30 years and is twice as common in women as in men. People with IBS are the largest group of patients seen in general gastroenterology clinics (1 in 20 referrals). The prevalence of the condition in the general population is estimated to be between 10% and 20%. Recent trends indicate that the prevalence of IBS in older people is considerable, so that the condition is a possible diagnosis whenever an older person presents with unexplained abdominal symptoms. The true prevalence of IBS in the whole population may be higher than estimated because it is thought that many people with IBS symptoms do not seek medical advice. NHS Direct online data suggest that 75% of people with IBS symptoms using this service rely on self-care. Extrapolating these data suggests that around 1.6–3.9 million people in England and Wales seek medical help for IBS.
3.13 There are 3 types of IBS: IBS with constipation (IBS-C), IBS with diarrhoea (IBS-D), and IBS with alternating constipation and diarrhoea (IBS-A). People with chronic diarrhoea are often given a diagnosis of IBS-D if a definitive cause for the diarrhoea has not been identified. There is evidence suggesting that up to a third of people with a diagnosis of IBS-D have bile acid malabsorption. On this basis, around half a million people who are currently being treated for IBS-D in the NHS may actually have bile acid malabsorption for which potential diagnosis and treatment are available.
3.14 Crohn's disease is a common form of IBD. It is a chronic severe condition characterised by inflammation, ulcers and bleeding that can affect any part of the gastrointestinal tract but mostly commonly affects the small intestine, the colon or both. Crohn's disease can directly cause chronic diarrhoea, but people with the condition can also develop bile acid malabsorption. Crohn's disease is estimated to affect about 60,000 people in the UK, around 100 per 100,000 population.
3.15 Crohn's disease is sometimes treated by ileal resection. The prevalence of bile acid malabsorption in people with Crohn's disease in clinical remission who have had ileal resection is high (97%), so this group was excluded from this assessment because testing before treatment was considered not to be necessary. In people with Crohn's disease in clinical remission who have not had ileal resection, the prevalence is 54%.
3.16 In current practice, the main pathway that includes SeHCAT is set out in the 2003 British Society of Gastroenterology (BSG) guidelines for the investigation of chronic diarrhoea. These guidelines are currently being updated.
3.17 There is uncertainty about whether using SeHCAT reduces the use of other diagnostic tests and clinician visits. Some clinical specialists suggest that placing SeHCAT earlier in the pathway would not stop additional tests such as colonoscopy or flexible sigmoidoscopy being done. Other clinical specialists thought that a positive SeHCAT test earlier in the pathway would result in cost savings because people with chronic diarrhoea would then not have additional tests, which is currently the case.
3.18 After a definitive diagnosis of bile acid malabsorption, people can be treated with bile acid sequestrants that bind with bile acids in the small bowel and prevent the secretory action of bile acids on the colon. There are currently 3 bile acid sequestrants available: colestyramine, colestipol and colesevelam.
3.19 Colestyramine and colestipol are anion exchange resins that have a high affinity for bile acids in the gastrointestinal tract, and form complexes with them. An important disadvantage of colestyramine and colestipol is an unpleasant taste, which can lead to poor tolerance of and adherence to treatment. Other side effects include constipation, nausea, borborygmi, flatulence, bloating and abdominal pain.
3.20 Colesevelam is a newer bile acid sequestrant that forms a polymeric gel in the gastrointestinal tract. It binds to bile acids with higher affinity than colestyramine or colestipol. Colesevelam is available in tablet form, whereas colestyramine is only available in powder form, which some people find unpleasant. Colesevelam is much more expensive than colestyramine and colestipol, and it is not licensed to treat bile acid malabsorption.
3.21 The response to bile acid sequestrants varies among people who have diarrhoea due to bile acid malabsorption. For people with Crohn's disease and ileal resection, the response to bile acid sequestrants has been reported to be 60%. In people with Crohn's disease without ileal resection, the estimate of response to bile acid sequestrants was 40% and in people with a diagnosis of IBS-D the estimate was 70% (Smith et al. 2000). These estimates are derived from case-series data. The effectiveness of SeHCAT and the treatment of bile acid malabsorption have not been widely assessed in randomised trials.