To the Editor:
We thank Dr Gonzales and colleagues for their interest in our review paper.1
Our suggested algorithm recommends a 12-week therapeutic trial with an IBAT (ileal bile acid transporter) inhibitor at the point of clinical diagnosis of progressive familial intrahepatic cholestasis while awaiting genetic results. The algorithm suggests reassessment when genotype results become available and in the light of the subsequent clinical and biochemical response. It was intended that the algorithm should be dynamic and responsive to new findings.
When we produced our manuscript neither the important Gonzales paper2 or the guidelines on genetic cholestatic liver diseases of the European Association for the Study of the Liver3 were available. We would now agree that a therapeutic trial of ursodeoxycholic acid treatment is appropriate in suspected progressive familial intrahepatic cholestasis type 3. We also agree that a therapeutic trial of an IBAT inhibitor should be considered in those who do not fully respond to ursodeoxycholic acid, as their prognosis is very poor.2
Financial support
The authors did not receive any financial support to produce this manuscript.
Authors' contributions
PM drafted the initial response to which all authors subsequently contributed. All authors agreed with the final draft.
Conflict of interest
PM: consultant for Albireo Pharma. JQB: consultant for Albireo Pharma, Mirum, Orphalan, Astra-Zeneca and Intercept Pharmaceuticals. MG: consultant for Albireo Pharma, Mirum and Orphalan. GI: consultant for Albireo Pharma, Mirum and Kedrion Pharma. EL: speaker agreements with Albireo Pharma, Mirum, Nutiricia and Takeda. PT: consultant for Albireo Pharma, GSK, Dr Falk Pharma, Gilead Medical, Advanz/Intercept Pharmaceuticals, Pliant Pharma, Cymabay. Grant Support from BMS, GSK, Dr Falk Pharma, Gilead Medical, Advanz/Intercept Pharmaceuticals, Regeneron, the Wellcome Trust, the Medical Research Foundation, Life- Arc, Innovate UK and NIHR.
Please refer to the accompanying ICMJE disclosure forms for further details.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.jhepr.2025.101402.
Appendix A. Supplementary data
The following are the Supplementary data to this article:
References
- 1.McKiernan P., Bernabeu J.Q., Girard M., et al. Opinion paper on the diagnosis and treatment of progressive familial intrahepatic cholestasis. JHEP Rep. 2023;6 doi: 10.1016/j.jhepr.2023.100949. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Gonzales E., Gardin A., Almes M., et al. Outcomes of 38 patients with PFIC3: impact of genotype and of response to ursodeoxycholic acid therapy. JHEP Rep. 2023;5 doi: 10.1016/j.jhepr.2023.100844. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.European Association for the Study of the Liver EASL Clinical Practice Guidelines on genetic cholestatic liver diseases. J Hepatol. 2024;81:303–325. doi: 10.1016/j.jhep.2024.04.006. [DOI] [PubMed] [Google Scholar]
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