# Challenges in the diagnosis and treatment of genetic cholestasis in adults

## TL;DR

This paper discusses the challenges in diagnosing and treating genetic cholestasis in adults, emphasizing the role of genetic variants and new treatment options.

## Contribution

The paper highlights the complexity of diagnosing genetic cholestasis in adults and introduces recent pharmacological treatment advances.

## Key findings

- Genetic variants contribute to both primary cholestasis and cholangiopathies in adults.
- Pharmacological interruption of bile acid circulation offers specific treatment options.
- Multidisciplinary discussions are recommended to improve diagnosis and management.

## Abstract

Disorders of bile formation and bile flow along the intra- and extrahepatic bile ducts are summarised under the term cholestasis. Clinically, conditions resulting in retention of biliary constituents such as bile acids within hepatocytes (termed primary cholestasis) need to be distinguished from diseases characterised by bile duct injury (termed cholangiopathies). Some cholangiopathies may also cause retention of biliary constituents within hepatocytes, resulting in secondary cholestasis. Genetic variants in a multitude of genes can contribute to the development of both primary cholestasis and cholangiopathies. Assessing the contribution of identified genetic variants to the clinical presentation in adults is complicated by factors such as environmental exposure, comorbidities, and medication intake. The diagnostic workup in adults with cholestasis should first consider common causes of primary cholestasis and cholangiopathies. If the aetiology remains unclear, liver histology and/or genetic testing should be pursued. Until recently, treatment for these conditions was largely supportive. However pharmacological interruption of the enterohepatic circulation of bile acids now offers the possibility of more specific intervention. Moreover, for those conditions in which the bile duct epithelium is the main site of injury, ursodeoxycholic acid remains essential. Multidisciplinary case discussions can help facilitate diagnosis and guide management.

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