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Chapter 13 - Familial Hepatocellular Cholestasis

from Section II - Cholestatic Liver Disease

Published online by Cambridge University Press:  19 January 2021

By
Frederick J. Suchy ,
Shikha S. Sundaram  and
Benjamin L. Shneider
Edited by
Frederick J. Suchy ,
Ronald J. Sokol  and
William F. Balistreri
Edited in association with
Jorge A. Bezerra ,
Cara L. Mack  and
Benjamin L. Shneider
Frederick J. Suchy
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Ronald J. Sokol
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
William F. Balistreri
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Jorge A. Bezerra
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Cara L. Mack
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Benjamin L. Shneider
Affiliation:
Texas Children’s Hospital, Houston
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Summary

Inherited cholestasis of hepatocellular origin has long been described in the neonate or during the first year of life [1]. Many of these infants were categorized as having idiopathic neonatal hepatitis after biliary atresia, metabolic diseases, and congenital infections were excluded [2]. The prognosis in familial cholestasis was poor compared with sporadic cholestasis that sometimes had an identifiable etiology. As the clinical and genotypic heterogeneity of these inherited disorders has become apparent, it is now recognized that patients may present initially and progress to end-stage liver disease at ages ranging from infancy to adulthood [3, 4].There may be significant overlap in clinical features such as intense pruritus and a low serum concentration of gamma-glutamyltransferase (GGT). The histopathology, immunohistochemical staining, and hepatic ultrastructure may provide additional diagnostic clues as to the underlying defect. However, next generation sequencing including use of targeted gene panels has proven of great value in rapidly and reliably discriminating cholestatic diseases of childhood, may suggest therapy with varying success based on the genotype of the patient, and has advanced our understanding of molecular mechanisms of bile secretion and acquired cholestasis [5]. It is not surprising that, so far, mutations in three genes encoding ATP-dependent transport proteins localized to the canalicular membrane that result in progressive cholestasis and liver injury have been discovered. The features of these disorders are compared in Table 13.1. Other genes encoding proteins involved in membrane transport, vesicular trafficking, and integrity of the cell junction may also be mutated in some patients. Mutations in the genes responsible for PFIC may be found in some adults with cryptogenic cholestasis and women with cholestasis of pregnancy including in the heterozygous state [6]. Owing to an immaturity of hepatic excretory function, cholestasis may occasionally occur in inherited diseases because of systemic illness rather than a primary defect in the liver (see Table 9.1). These disorders will not be considered in this review.

Type
Chapter
Information
Liver Disease in Children , pp. 204 - 221
Publisher: Cambridge University Press
Print publication year: 2021

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References

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