Cholesterol Crystal Nucleation: A Decade–Long Search for the Missing Link in Gallstone Pathogenesis

Cholesterol gallstones form after a series of pathological events occurs in both the liver and the gallbladder. These events include hepatic secretion of cholesterol supersaturated bile, nucleation and growth of cholesterol monohydrate crystals in the gallbladder and impaired emptying of gallbladder contents (1). In 1979, nucleation of cholesterol monohydrate crystals was identified as the earliest event in the evolution of cholesterol gallstones that reliably distinguishes patients who form gallstones from normal patients (2). Despite an intensive, decade-long search to identify the factors that influence cholesterol crystal nucleation in lithogenic bile, our understanding of the pathophysiology of cholesterol gallstone formation remains fragmentary and incomplete.