The disease is typically progressive, leading to fulminant liver failure and death in childhood, in the absence of liver transplantation. Hepatocellular carcinoma may develop in PFIC-2 at a very early age; even toddlers have been affected.

Progressive familial intrahepatic cholestasis (PFIC) is a group of familial cholestatic conditions caused by defects in biliary epithelial transporters. The clinical presentation usually occurs first in childhood with progressive cholestasis. This usually leads to failure to thrive, cirrhosis, and the need for liver transplantation.

The causes of intrahepatic cholestasis of pregnancy are still not fully understood. Hormones and genetic factors are likely to be important in the pathogenesis of the disease. A number of features of the disease suggest a link to hormones:

- ICP occurs in the third trimester at the time when hormone levels are at their highest.

- Twin and triplet pregnancies, which are associated with higher hormone levels, show a higher incidence of ICP.

- ICP resolves quickly after delivery, when placental hormone production ceases.

- Older high-dose estrogen oral contraceptive pills could cause features of ICP.

Estrogens, and particularly glucuronides such as estradiol-17β-D-glucuronide, have been shown to cause cholestasis in animal studies, by reducing bile acid uptake by hepatocytes.