Imperial College London

Shahid A Khan

Faculty of MedicineFaculty of Medicine Centre

Professor of Practice (Haematology)
 
 
 
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Contact

 

+44 (0)20 3312 6254shahid.khan

 
 
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Location

 

Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Appleby:2019:10.1371/journal.pone.0211348,
author = {Appleby, R and Moghul, I and Khan, S and Yee, M and Manousou, P and Dew, Neal T and Walters, J},
doi = {10.1371/journal.pone.0211348},
journal = {PLoS ONE},
title = {Non-alcoholic fatty liver disease is associated with dysregulated bile acid synthesis and diarrhea: a prospective observational study},
url = {http://dx.doi.org/10.1371/journal.pone.0211348},
volume = {14},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - BackgroundNon-alcoholic fatty liver disease (NAFLD) may be associated with changes in bile acid (BA) metabolism. Hepatic BA production, measured by serum levels of the precursor 7α-hydroxy-4-cholesten-3-one (C4), is regulated by the farnesoid-X-receptor (FXR)-dependent ileal hormone fibroblast growth factor 19 (FGF19). Low FGF19 and high C4 are features of chronic BA diarrhea. Obeticholic acid, an FXR agonist, stimulates FGF19 and has shown therapeutic potential in both BA diarrhea and in NAFLD. We hypothesized there are associations of FGF19, C4 and BA diarrhea with NAFLD.Methods and findings127 patients with known NAFLD were recruited prospectively. Clinical features, including metformin use, markers of NAFLD severity and BA synthesis were analyzed. The overall incidence of chronic diarrhea was 25%, with features of BA diarrhea in 12%. FGF19 negatively correlated with C4 (rs = -0.43, p = 0.001) and with alanine aminotransferase (rs = -0.22, p = 0.03), but not with either NAFLD fibrosis or Fibroscan scores. High C4 was associated with a higher NAFLD fibrosis score (p < 0.05), and with diarrhea (p = 0.001). The median NAFLD fibrosis score was higher in those with diarrhea (p = 0.002). Metformin use, in 44% overall, was particularly associated with diarrhea (in 36% vs 17%, p = 0.02), and a lower median FGF19 (74 vs 105 pg/mL, p < 0.05).ConclusionsIncreased hepatic BA production and diarrhea, but not low FGF19, were associated with increased NAFLD fibrosis score, indicating dysregulation of the FXR-FGF19 axis and suggesting hepatic FGF19 resistance. Metformin use was an important factor in a subgroup, lowering FGF19, and resulting in bile acid diarrhea.
AU - Appleby,R
AU - Moghul,I
AU - Khan,S
AU - Yee,M
AU - Manousou,P
AU - Dew,Neal T
AU - Walters,J
DO - 10.1371/journal.pone.0211348
PY - 2019///
SN - 1932-6203
TI - Non-alcoholic fatty liver disease is associated with dysregulated bile acid synthesis and diarrhea: a prospective observational study
T2 - PLoS ONE
UR - http://dx.doi.org/10.1371/journal.pone.0211348
UR - http://hdl.handle.net/10044/1/67130
VL - 14
ER -