Hepatocellular and Intrahepatic Cholestasis

Intrahepatic cholestasis is abnormal intrahepatic bile flow due to defects in any number of hepatocyte or cholangiocyte proteins that alter the synthesis, transport, or secretion of bile components, in the absence of structural alterations to the liver or biliary tree. Although congenital infections, endocrine abnormalities, medication effects, and the like may cause cholestasis, for the purposes of this chapter, intrahepatic cholestasis is synonymous with primary (genetic) cholestasis—and since the last edition of this book, perhaps no topic has seen more progress. While the clinical description, involved genes, and pathophysiologic mechanisms involved in a variety of cholestatic diseases were previously characterized, the explosion in clinical genomics has uncovered new genes, and new variants in previously recognized genes. The result is increased recognition of a spectrum of clinical phenotypes associated with cholestasis genes, beyond simply neonatal cholestasis.