We have read with interest the comments [
Comment on: “Serum bile acids in cystic fibrosis patients – glycodeoxycholic acid
as a potential marker of liver disease”.
] on our recent article, which showed that glycodeoxycholic acid discriminates between
cystic fibrosis (CF) patients with non-cirrhotic liver involvement and no detectable
disease (AUC: 0.924, 95%CI 0.822–1.000, p
< 0.001) [
- Drzymała-Czyż S.
- Dziedzic K.
- Szwengiel A.
- Krzyżanowska-Jankowska P.
- Nowak J.K.
- Nowicka A.
- et al.
Serum bile acids in cystic fibrosis patients - glycodeoxycholic acid as a potential
marker of liver disease.
]. Given this result, we do not share the concern that sample size is an issue. Please
note that to include 25 patients with liver cirrhosis, as defined in our study, we
needed to screen almost 1000 patients in total (nearly half of the national population).
Our prospective work on the bile acid profile is also not easily comparable with the
retrospective clinical analysis by Colombo et al. (in which one of the authors was
involved), where the bile acids were not measured [
- Colombo C.
- Alicandro G.
- Oliver M.
- Lewindon P.J.
- Ramm G.A.
- Ooi C.Y.
- et al.
Ursodeoxycholic acid and liver disease associated with cystic fibrosis: a multicenter
]. Interestingly, that research revealed the non-significantly higher crude cumulative
incidence of portal hypertension in patients treated in centers prescribing ursodeoxycholic
acid (UDCA) as compared to those followed by centers not applying UDCA ((10.1% (95%
CI: 7.9–12.3) vs. 7.7% (95% CI: 4.6–10.7)). Second, key clinical characteristics proposed
in the correspondence are already reported in the article, including exocrine pancreatic
status and individual CFTR mutations (all the mutations in all patients). Besides,
we did assess whether bile acid concentrations differ between CF patients with cirrhosis,
other liver involvement and no liver disease – in groups that, by definition, could
not be equal and should not be matched. Third, it was suggested that we did not present
data on bile acids other than glycodeoxycholic acid. Please note that seven other
bile acids were also measured, and their levels were summarized in table 2 in the
original article. Fourth, the research on ivacaftor [
- van de Peppel I.P.
- Doktorova M.
- Berkers G.
- de Jonge H.R.
- Houwen R.H.J.
- Verkade H.J.
- et al.
IVACAFTOR restores FGF19 regulated bile acid homeostasis in cystic fibrosis patients
with an S1251N or a G551D gating mutation.
] cited in the letter does not directly apply to our study because there were no patients
mutations S1251N or G551D. In addition, our work was conducted at a time when combined
therapy was not yet available. Fifth, the current study only included patients in
stable condition who did not require antimicrobial therapy in the previous six weeks
(specified in the methods section). The article referenced in the correspondence does
not refer to bile acids measured in the serum, but in the broncho-alveolar lavage
(BAL), and the bile acids were likely to “reach the lower airways through duodenogastroesophageal
- Flynn S.
- Reen F.J.
- Caparrós-Martín J.A.
- Woods D.F.
- Peplies J.
- Ranganathan S.C.
- et al.
Bile acid signal molecules associate temporally with respiratory inflammation and
microbiome signatures in clinically stable cystic fibrosis patients.
], which is not immediately related to the current study. Documented “temporal links
between bile acids and inflammatory markers” reflected a different aspect of the disease.
We hope that the above discussion will help to lift the presented concerns.