Opinion paper on the diagnosis and treatment of progressive familial intrahepatic cholestasis

Patrick McKiernan; Jesus Quintero Bernabeu; Muriel Girard; Giuseppe Indolfi; Eberhard Lurz; Palak Trivedi

doi:10.1016/j.jhepr.2023.100949

Opinion paper on the diagnosis and treatment of progressive familial intrahepatic cholestasis

JHEP Rep. 2023 Oct 27;6(1):100949. doi: 10.1016/j.jhepr.2023.100949. eCollection 2024 Jan.

Authors

Patrick McKiernan¹, Jesus Quintero Bernabeu², Muriel Girard³, Giuseppe Indolfi^{4

5}, Eberhard Lurz⁶, Palak Trivedi^{7

8

9}

Affiliations

¹ Liver Unit and Small Bowel Transplantation, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
² Pediatric Hepatology and Liver Transplant Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
³ Pediatric Hepatology Unit, Hôpital Necker-Enfants Malades, and Université Paris Cité, Paris, France.
⁴ Paediatric and Liver Unit, Meyer Children's Hospital IRCCS, Florence, Italy.
⁵ Department NEUROFARBA, University of Florence, Florence, Italy.
⁶ Dr. von Hauner Children's Hospital, LMU Munich University Hospital, Munich, Germany.
⁷ National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Centre for Liver and Gastrointestinal Research, University of Birmingham College of Medical and Dental Sciences, Birmingham, UK.
⁸ Institute of Immunology and Immunotherapy, University of Birmingham College of Medical and Dental Sciences, Birmingham, UK.
⁹ Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.

Abstract

Background & aims: Progressive familial intrahepatic cholestasis (PFIC) relates to a group of rare, debilitating, liver disorders which typically present in early childhood, but have also been reported in adults. Without early detection and effective treatment, PFIC can result in end-stage liver disease. The aim of the paper was to put forward recommendations that promote standardisation of the management of PFIC in clinical practice.

Methods: A committee of six specialists came together to discuss the challenges faced by physicians in the management of PFIC. The committee agreed on two key areas where expert guidance is required to optimise care: (1) how to diagnose and treat patients with a clinical presentation of PFIC in the absence of clear genetic test results/whilst awaiting results, and (2) how to monitor disease progression and response to treatment. A systematic literature review was undertaken to contextualise and inform the recommendations.

Results: An algorithm was developed for the diagnosis and treatment of children with suspected PFIC. The algorithm recommends the use of licensed inhibitors of ileal bile acid transporters as the first-line treatment for patients with PFIC and suggests that genetic testing be used to confirm genotype whilst treatment is initiated in patients in whom PFIC is suspected. The authors recommend referring patients to an experienced centre, and ensuring that monitoring includes measurements of pruritus, serum bile acid levels, growth, and quality of life following diagnosis and during treatment.

Conclusions: The algorithm presented within this paper offers guidance to optimise the management of paediatric PFIC. The authors hope that these recommendations will help to standardise the management of PFIC in the absence of clear clinical guidelines.

Impact and implications: This opinion paper outlines a consistent approach to the contemporaneous diagnosis, monitoring, referral and management of children with progressive familial intrahepatic cholestasis. This should assist physicians given the recent developments in genetic diagnosis and the availability of effective drug therapy. This manuscript will also help to raise awareness of current developments and educate health planners on the place for new drug therapies in progressive familial intrahepatic cholestasis.

Keywords: IBAT inhibitor; PFIC; diagnosis; treatment.