Clinics and Research in Hepatology and Gastroenterology
Mini reviewLiver involvement in children with ciliopathies
Introduction
Ciliopathies are a heteregeneous group of disorders due to cilia abnormalities. Ciliopathy without liver or kidney involvement is rare. In case of combined kidney and liver involvement, ciliopathies are also called hepatorenal fibrocystic disorders. The aim of this review is to briefly explain the pathophysiology of ciliopathies, the role of the ductal plate malformation in liver involvement and to offer a brief clinical overview focusing on congenital hepatic fibrosis (CHF), Caroli syndrome (CS), Caroli disease (CD) and other fibrocystic liver diseases.
Section snippets
Abnormalities of the primary cilia
There are two kinds of cilia: motile and immotile. In respiratory epithelium, fallopian tube epithelium, ependymal cells and sperm, cilia are motile and transport fluid along the epithelial surface through concerted movement. When motile cilia are non-functional, they cause primary ciliary dyskinesias with symptoms of bronchiectasis, situs inversus and infertility [1], [2]. Most other cells possess primary cilia, which are non-motile. This sensory organelle extends outward from the cell surface
Ciliopathies
Over the last decade several genes associated with ciliopathies have been identified, and understanding their function has shed light on the pathophysiology of ciliopathies [1], [5], [15]. Generally, ciliopathies are multisystemic disorders, often sharing common features, such as polydactily, mental retardation, retinal defects, such as retinitis pigmentosum and polycystic kidneys. Table 1 summarizes the different types of ciliopathies. [4], [5], [16].
Liver involvement in ciliopathies
CHF and CD are the most common liver manifestations of ciliopathies in children. Here, we will describe CHF and Caroli disease and present other fibrocystic liver disorders in table form. In addition, we will elaborate on the group of ciliopathies known as hepatorenal fibrocystic disease for whom we will suggest a practical approach to diagnose liver involvement.
Conclusion
There is increasing understanding of the genetics and clinical manifestations of ciliopathies. Although the kidney, brain and retina are most frequently affected, liver involvement must be recognized because it may progress to life-threatening portal hypertension or cholangitis, possibly warranting liver transplantation.
Disclosure of interest
The authors declare that they have no conflicts of interest concerning this article.
Acknowledgements
We gratefully acknowledge Mrs Sylvia Udry-Moulin for her assistance with illustrations, Dr Anooshiravani-Dumont for providing illustrative imaging and Dr Rougemont for providing examples of histology.
References (36)
- et al.
Decoding cilia function: defining specialized genes required for compartmentalized cilia biogenesis
Cell
(2004) - et al.
Cholangiocyte cilia detect changes in luminal fluid flow and transmit them into intracellular Ca2+ and cAMP signaling
Gastroenterology
(2006) - et al.
Congenital hepatic fibrosis in children
J Pediatr
(1981) - et al.
Congenital fibrocystic liver diseases
Best Pract Res Clin Gastroenterol
(2010) - et al.
Hepatobiliary fibropolycystic diseases: a clinical and histological review of 51 patients
J Hepatol
(1986) - et al.
Imaging findings in congenital hepatic fibrosis
E J Radiol
(2007) - et al.
Phenotypic heterogeneity in pediatric autosomal dominant polycystic kidney disease at first presentation: a single-centre, 20-year review
Am J Kidney Dis
(2004) - et al.
Polycystic kidney disease in the first year of life
J Pediatr
(1987) - et al.
When cilia go bad: cilia defects and ciliopathies
Nat Rev Mol Cell Biol
(2007) The importance of a single primary cilium
Organogenesis
(2013)
Ciliopathies: an expanding disease spectrum
Pediatr Nephrol
A systems biology approach to understanding the ciliopathy disorders
Genome Med
Isolation and characterization of cholangiocyte primary cilia
Am J Physiol Gastrointest Liver Physiol
Cholangiocyte primary cilia in liver health and disease
Dev Dyn
Cholangiociliopathies: genetics, molecular mechanisms and potential therapies
Curr Opin Gastroenterol
Pathogenesis of ductal plate malformation
J Gastroenterol Hepatol
The ductal plate malformation
Acta Pathol Microbiol Scand Suppl
Detection of apoptosis and expression of apoptosis-related proteins during human intrahepatic bile duct development
Am J Pathol
Cited by (44)
Evaluation of living donors for hereditary liver disease (siblings, heterozygotes)
2023, Journal of HepatologyBiliary Atresia – emerging diagnostic and therapy opportunities
2021, EBioMedicineCitation Excerpt :Primary cilia play an important role for Hedgehog signalling [86] and it will be interesting to explore to what extent Hedgehog signalling is perturbed in BA. This may also shed light on cilia dysfunction in other liver diseases, such as neonatal sclerosing cholangitis and polycystic liver disease [16,87,88]. Beta-amyloid deposits in the form of neural plaques is a hallmark of Alzheimer's disease, but recently, Babu et al. (2020) showed that beta-amyloid also accumulates in livers in BA patients as well as in the RRV mouse model and in BA organoids (see above) [54].
Neonatal Assessment of Infants with Heterotaxy
2020, Clinics in PerinatologyCitation Excerpt :Although β-agonists may promote ciliary function, further investigation will need to identify which patients may benefit most, particularly given the frequent utilization of β-blockade in patients with cardiac dysfunction.32,61–64 Ciliopathies have additionally been implicated in hepatic fibrosis, potentially increasing the risk for post-Fontan liver disease in patients with single ventricle physiology.65–68 Although liver transplant may be successful in these circumstances, the presence of additional anatomic anomalies, progressive multiorgan dysfunction, and complex anesthesia concerns may make surgical planning challenging.44,45,60,69
Genetic Contributions to Biliary Atresia: A Developmental Cholangiopathy
2023, Seminars in Liver Disease