Bile Formation and Pathophysiology of Gallstones

Gallstone disease is one of the most prevalent digestive diseases worldwide, leading to a considerable financial and social burden. Epidemiological and clinical studies have clearly demonstrated that a complex genetic basis plays a key role in determining individual predisposition to develop gallstones in response to environmental factors. For cholesterol gallstones, the primary pathogenic factor is persistent hepatic hypersecretion of biliary cholesterol induced by multiple Lith genes, with insulin resistance as part of the metabolic syndrome interacting with environmental cholelithogenic factors to cause the phenotype. Pigment gallstones are caused by abnormal bilirubin metabolism and are pigmented, associated with or without biliary infection, as a result of massive precipitation of unconjugated bilirubin and calcium bilirubinate. The latest advances in the gallstone pathogenesis will facilitate the development of a novel, effective, and noninvasive therapy for patients with gallstones.