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Review
. 2022 Aug 18;11(16):2570.
doi: 10.3390/cells11162570.

Rare Inherited Cholestatic Disorders and Molecular Links to Hepatocarcinogenesis

Rebecca Jeyaraj  1 , Deirdre Kelly  2   3
Affiliations
Review

Rare Inherited Cholestatic Disorders and Molecular Links to Hepatocarcinogenesis

Rebecca Jeyaraj et al. Cells. .

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer affecting adults and the second most common primary liver cancer affecting children. Recent years have seen a significant increase in our understanding of the molecular changes associated with HCC. However, HCC is a complex disease, and its molecular pathogenesis, which likely varies by aetiology, remains to be fully elucidated. Interestingly, some inherited cholestatic disorders that manifest in childhood are associated with early HCC development. This review will thus explore how three genes that are associated with liver disease in childhood (ABCB11, TJP2 and VPS33B) might play a role in the initiation and progression of HCC. Specifically, chronic bile-induced damage (caused by ABCB11 changes), disruption of intercellular junction formation (caused by TJP2 changes) and loss of normal apical-basal cell polarity (caused by VPS33B changes) will be discussed as possible mechanisms for HCC development.

Keywords: ABCB11 gene; TJP2 gene; VPS33B gene; hepatocarcinogenesis; hepatocellular carcinoma; inherited cholestasis.

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Conflict of interest statement

The authors declare no conflict of interest. Funders had no role in the conceptualisation of the article, in the interpretation of evidence, in the writing of the manuscript or in the decision to publish the article.

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