Genetics of Hepatobiliary Diseases Brian D. Juran, Konstantinos N. Lazaridis  Clinical Gastroenterology and Hepatology  Volume 4, Issue 5, Pages 548-557 (May 2006) DOI: 10.1016/j.cgh.2006.03.004 Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

Figure 1 Cholesterol, bile salt, and phospholipid homeostasis. Hepatic cholesterol results from HMG-CoA reductase mediated conversion of acetate and uptake of plasma cholesterol via the low-density lipoprotein receptor (LDLR). Elimination of the cholesterol from the hepatocyte occurs through direct transport to the bile or by conversion to bile acid (BA) by CYP7A1. Buildup of intracellular bile acid levels through synthesis from cholesterol and uptake of circulating bile acids via Na+ dependent taurocholate cotransporting peptide (NTCP) activates the bile-acid sensor farnesoid X receptor (FXR), stimulating bile salt and phospholipid efflux through induction of ABCB11 and ABCB4 as well as repressing further bile acid synthesis by feedback inhibition of CYP7A1 via small heterodimer partner (SHP). Bile salts and phospholipids combine in the bile to form mixed micelles, which act to solubilize cholesterol. When the ability of the mixed micelles to maintain cholesterol solubility is exceeded, gallstones might form. Clinical Gastroenterology and Hepatology 2006 4, 548-557DOI: (10.1016/j.cgh.2006.03.004) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

Figure 2 Imaging of PCLD. Abdominal computed tomography scan of a patient with PCLD; the entire liver parenchyma is replaced by cystic lesions. Clinical Gastroenterology and Hepatology 2006 4, 548-557DOI: (10.1016/j.cgh.2006.03.004) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions