Bile acid malabsorption, known also as Bile acid diarrhea, is a cause of chronic diarrhea.
It has also been called Bile acid-induced diarrhea, Cholerheic or Choleretic enteropathy
and Bile salt malabsorption.
It can result from malabsorption secondary to gastro-intestinal disease, or be a primary
disorder, associated with excessive bile acid production.
Treatment with bile acid sequestrants is often effective.
Classification Bile acid malabsorption was first recognized
in patients with ileal disease.
When other causes were recognized, and an idiopathic, primary form described, a classification
into three types was proposed: Type 1: Bile acid malabsorption, secondary
to ileal resection, or ileal inflammation Type 2: Idiopathic bile acid malabsorption,
Primary bile acid diarrhea Type 3: Secondary to various gastrointestinal
diseases including cholecystectomy, vagotomy, small intestinal bacterial overgrowth, radiation
enteropathy, celiac disease, chronic pancreatitis, etc.
Mechanisms of disease Enterohepatic circulation of bile salts
Bile acids are produced in the liver, secreted into the biliary system, stored in the gall-bladder
and are released after meals stimulated by cholecystokinin.
They are important for the digestion and absorption of fats in the small intestine.
Usually over 95% of the bile acids are absorbed in the terminal ileum and are taken up by
the liver and resecreted.
This enterohepatic circulation of bile acids takes place 4-6 times in 24 hours and usually
less than 0.5g /24h of bile acids enter the large intestine.
When larger amounts of bile acids enter the large intestine, they stimulate water secretion
and intestinal motility in the colon, which causes symptoms of chronic diarrhea.
Intestinal absorption of bile acids The ileum is very efficient at absorbing the
glyco- and taurine-conjugated forms of the bile salts.
The apical sodium-dependent bile salt transporter is the first step in absorption at the brush-border
membrane.
The cytoplasmic ileal bile acid binding protein and the basolateral heterodimer of OSTα and
OSTβ transfer bile acids through and out of the cell where they eventually enter the
portal vein.
These bile acid transporters are all highly expressed in the ileum but not in the liver,
jejunum or colon.
When expression of these specialized transporters is reduced, the intestine is less efficient
at bile acid reabsorption.
If intestinal motility is affected by gastro-intestinal surgery, or bile acids are deconjugated by
small intestinal bacterial overgrowth, absorption is less efficient.
A very small proportion of the patients with no obvious disease may have mutations in ASBT,
but this mutation is not more common in most patients and does not affect function.
Overproduction of bile acids Primary bile acid diarrhea may be caused by
an overproduction of bile acids.
Several groups of workers have failed to show any defect in ileal bile acid absorption in
these patients, and they have an enlarged bile acid pool, rather than the reduced pool
expected with malabsorption.
The synthesis of bile acids in the liver is negatively regulated by the ileal hormone
fibroblast growth factor 19, and lower levels of this hormone result in overproduction of
bile acids, which are more than the ileum can absorb.
Diagnosis Several methods have been developed to identify
the disorder but there are difficulties with all of them.
Fecal bile acid quantification is unpleasant for both the patient and laboratory.
Diagnosis of bile acid malabsorption is easily and reliably made by the SeHCAT test.
This nuclear medicine test involves two scans a week apart and so measures multiple cycles
of bile acid excretion and reabsorption.
There is limited radiation exposure.
Retention of SeHCAT at 7 days is normally above 15%; values less than 15%, 10% and 5%
predict respectively mild, moderate and severe abnormal retention and an increasing likelihood
of response to bile acid sequestrants.
This test is not licensed in the USA, and is underutilized even where it is available.
Older methods such as the 14C-glycocholic breath test are no longer in routine clinical
use.
Measurement of 7 alpha-hydroxy-4-cholesten-3-one, a bile acid precursor, in serum, shows the
increased bile acid synthesis found in bile acid malabsorption.
This test is an alternative diagnostic means when available.
Fasting blood FGF19 values may have value in the recognition of the disease and prediction
of response.
Prevalence Bile acid malabsorption is common in Crohn's
disease but not always recognised.
Most patients with previous ileal resection and chronic diarrhea will have abnormal SeHCAT
tests and can benefit from bile acid sequestrants.
Patients with primary bile acid diarrhea are frequently misdiagnosed as having the irritable
bowel syndrome as clinicians fail to recognize the condition.
When SeHCAT testing is performed, the diagnosis of primary bile acid diarrhea is commonly
made.
In a review of 18 studies of the use of SeHCAT testing in diarrhea-predominant irritable
bowel syndrome patients, 32% of 1223 patients had a SeHCAT 7-day retention of less than
10%, and 80% of these reported a response to cholestyramine, a bile acid sequestrant.
Estimates of the population prevalence taken from this review suggest that 1% of the adult
population could have primary bile acid diarrhea.
Treatment Bile acid sequestrants are the main agents
used to treat bile acid malabsorption.
Cholestyramine and colestipol, both in powder form, have been used for many years.
Unfortunately many patients find them difficult to tolerate; although the diarrhea may improve,
other symptoms such as pain and bloating may worsen.
Colesevelam is a tablet and some patients tolerate this more easily.
References