Mini review
Liver involvement in children with ciliopathies

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Summary

Abnormalities in primary cilia lead to diseases called ciliopathies. Multiple organ involvement is the norm since primary cilia are present in most cells. When cholangiocyte cilia are abnormal, ductal plate malformation ensues leading to such conditions as congenital hepatic fibrosis, Caroli disease or syndrome, or other fibrocystic disease.

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.

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