Recent developments in diagnosing bile acid diarrhea

ABSTRACT

Introduction

Bile acid diarrhea (BAD) commonly causes chronic diarrhea. Symptoms may be mistaken for disorders of gut brain interaction. Due to the lack of widely available diagnostic tests and poor recognition of BAD, there is a delay in diagnosis leading to increased healthcare system burden and decreased patient quality of life.

Areas covered

A thorough review of the literature was conducted using PubMed for articles on the biological functions of bile acids, pathophysiology and management of BAD, but focusing on diagnostic testing including ⁷⁵SeHCAT retention, 7αC4, FGF-19, fecal bile acids, and single stool tests. This narrative review discusses available modalities focusing on noninvasive stool and serum testing that are more widely available and show good sensitivity and specificity for diagnosis of BAD. ⁷⁵SeHCAT retention is not available in many countries. Alternative diagnostic tests include total and primary fecal bile acid (BA) excretion in 48-hour collection or a single stool sample, serum7αC4 >46 or 52.5 ng/mL, and combination of single stool and serum 7αC4 ±watery stools (Bristol Stool Form Scale 6–7).

Expert opinion

Given the ease of serum and single stool sample acquisition and diagnostic advances, clinical practice should embrace positive diagnosis, rather than BAS therapeutic trial. BAD needs to be considered in diverse gastrointestinal diseases.

KEYWORDS:

• Sequestrants
• malabsorption
• chronic diarrhea
• SeHCAT
• 7αC4
• FGF-19
• diarrhea-predominant irritable bowel syndrome
• inflammatory bowel disease

Article highlights

• Bile acid diarrhea (BAD) is a common but underdiagnosed cause of chronic watery diarrhea with symptoms that overlap with those of disorders of gut–brain interaction (DGBI) including functional diarrhea and diarrhea-predominant irritable bowel syndrome.

• BAD causes significant impairment in quality of life, given severe urgency and high prevalence of occasional fecal incontinence. When diagnosed, BAD can be effectively treated with bile acid sequestrants.

• The gold standard for diagnosis is the ⁷⁵SeHCAT; however, this is not available in the United States.

• Most recent noninvasive tests have shown good sensitivity and specificity in the screening and diagnosis of BAD. These include the following:

• fasting serum 7αC4

• 48-hour total fecal bile acid excretion

• single stool bile acid

• combined fasting serum 7αC4 and single stool total or primary bile acid test

• The test that has shown the best combination of diagnostic performance as well as patient acceptability so far is the combined serum 7αC4 and single sample bile acid stool test. However, cutoff values for some of these measurements require further definition and validation.

• Due to the increased availability of objective diagnostic testing, a therapeutic trial with a bile acid sequestrant is no longer recommended.

Declaration of interests

Dr Camilleri’s lab performed single-center clinical trials in the last 5 years with tropifexor (Novartis Pharmaceuticals) and with aldafermin (NGM Pharma). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosure

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

M. Camilleri: Senior author; revised and finalized manuscript. C. Lupianez-Merly: Fellow coauthor; wrote 1st draft; revised and finalized manuscript. S. Dilmaghani: Fellow coauthor; revised and finalized manuscript.

Additional information

Funding

This paper was not funded.