Genetic Determinants of Drug-induced Cholestasis and Intrahepatic Cholestasis of Pregnancy

Christiane Pauli-Magnus, M.D.; Peter J. Meier, M.D.; Bruno Stieger, Ph.D.


Semin Liver Dis. 2010;30(2):147-159. 

In This Article


From the examples provided in this article it is apparent that the genetically determined dysfunction of hepatocellular uptake and excretion of bile salts is an important pathogenic factor for the development of cholestasis. Although the genetic components of ICP and estrogen-induced cholestasis have clearly been established over the last decade, the role of genetics in drug-induced cholestasis is less evident. The heterogeneous and multifactorial nature of drug-induced liver disease makes it not only challenging to clearly link liver disease to a specific drug, but so far impossible to prove the pathogenic role of a specific genetic transporter variant. Future challenges will consist in integrating different genetic determinants of drug toxicity with different environmental and comorbidity-related factors and in a comprehensive system, allowing the cautious use of problematic drugs in susceptible patients.


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