Cholesterol gallstones occur when at least three simultaneous defects are present: (i) cholesterol supersaturation of bile with formation of cholesterol-rich unstable vesicles; (ii) accelerated crystallisation of cholesterol in bile owing to a defect of crystallisation inhibiting or an abundance of crystallisation promoting factors; and (iii) prolonged bile stasis due to decreased gall bladder motility.1

Precipitation of solid cholesterol crystals from supersaturated bile has an essential role in cholesterol gallstone formation.2 ,3 The number of days it takes before microscopic plate-like cholesterol monohydrate crystals are observed in human bile has been referred to as the crystal nucleation time.2 This term, however, indicates early aggregation of cholesterol molecules from supersaturated bile into submicroscopic nuclei.4 This crucial step is followed by precipitation, growth and agglomeration of cholesterol crystals, which then become visible at light microscopy. In this respect, the term crystal detection time seems more appropriate than crystal nucleation time.5 Recent data indicate that solid cholesterol can also precipitate as crystal forms other than plate-like structures,6-8 suggesting that crystallisation in bile is a rather complex phenomenon.

The study of pathways leading to cholesterol crystallisation in bile has clinical relevance as the appearance of biliary crystals reliably distinguishes between patients with and without cholesterol gallstones.2 ,9 Crystallisation of cholesterol is faster in patients with multiple than in those with solitary stones,8 ,10-12 a finding which might be linked to the increased risk of gallstone recurrence after non-surgical treatment in patients with more than one stone.13-16 Moreover, a better understanding of the physical/chemical events occurring during crystallisation in bile would provide a useful method for the identification of factors delaying or preventing precipitation of cholesterol crystals and, therefore, gallstone formation in humans.

This article will discuss current views on the formation of cholesterol …