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Functional and motility disorders
Original research
Novel associations of bile acid diarrhoea with fatty liver disease and gallstones: a cohort retrospective analysis
  1. Richard N Appleby1,
  2. Jonathan D Nolan1,
  3. Ian M Johnston1,
  4. Sanjeev S Pattni1,2,
  5. Jessica Fox1,
  6. Julian RF Walters1
  1. 1 Division of Digestive Diseases, Imperial College London, London, UK
  2. 2 Department of Gastroenterology, University Hospitals of Leicester NHS Trust, Leicester, UK
  1. Correspondence to Professor Julian RF Walters; julian.walters{at}imperial.ac.uk

Abstract

Background Bile acid diarrhoea (BAD) is a common cause of chronic diarrhoea with a population prevalence of primary BAD around 1%. Previous studies have identified associations with low levels of the ileal hormone fibroblast growth factor 19 (FGF19), obesity and hypertriglyceridaemia. The aim of this study was to identify further associations of BAD.

Methods A cohort of patients with chronic diarrhoea who underwent 75selenohomocholic acid taurate (SeHCAT) testing for BAD was further analysed retrospectively. Additional clinical details available from the electronic patient record, including imaging, colonoscopy, chemistry and histopathology reports were used to calculate the prevalence of fatty liver disease, gallstones, colonic neoplasia and microscopic colitis, which was compared for BAD, the primary BAD subset and control patients with diarrhoea.

Findings Of 578 patients, 303 (52%) had BAD, defined as a SeHCAT 7d retention value <15%, with 179 (31%) having primary BAD. 425 had an alanine aminotransferase (ALT) recorded, 184 had liver imaging and 176 had both. Overall, SeHCAT values were negatively associated with ALT (rs=−0.19, p<0.0001). Patients with BAD had an OR of 3.1 for an ALT >31 ng/mL with imaging showing fatty liver (p<0.001); similar figures occurred in the primary BAD group. FGF19 was not significantly related to fatty liver but low levels were predictive of ALT >40 IU/L. In 176 subjects with gallbladder imaging, 27% had gallstones, 7% had a prior cholecystectomy and 34% either of these. The median SeHCAT values were lower in those with gallstones (3.8%, p<0.0001), or gallstones/cholecystectomy (7.2%, p<0.001), compared with normal gallbladder imaging (14%). Overall, BAD had an OR of 2.0 for gallstones/cholecystectomy (p<0.05). BAD was not significantly associated with colonic adenoma/carcinoma or with microscopic colitis.

Interpretation The diagnosis of BAD is associated with fatty liver disease and with gallstones. The reasons for these associations require further investigation into potential metabolic causes.

  • chronic diarrhoea
  • bile acid metabolism
  • nonalcoholic steatohepatitis
  • gallstone disease
  • cholecystectomy

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/bmjgast-2017-000178

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    Footnotes

    • Contributors RNA and JRFW devised the study, collected and analysed the data and drafted the manuscript. JDN, IMJ, SSP and JF collected data, contributed to the analysis and to the critical revision of the manuscript.

    • Funding The study was sponsored by Imperial College London. JRFW has served as a speaker, a consultant and an advisory board member for Albireo AB, GE Healthcare, Intercept Pharmaceuticals and Pendopharm. RNA has been supported by research funding from Albireo and Intercept. SSP, IMJ and JDN were supported by the BROAD research fund and/or by BRET. JF has no relevant disclosures.

    • Disclaimer This manuscript has been written in compliance with the STROBE guidance for cohort studies without any exception.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Inquiries regarding access to the data should be addressed to the corresponding author.