An update on the pathogenesis of cholesterol gallstone disease.

PURPOSE OF REVIEW: Gallstone disease is a major epidemiologic and economic burden worldwide, and the most frequent form is cholesterol gallstone disease.

RECENT FINDINGS: Major pathogenetic factors for cholesterol gallstones include a genetic background, hepatic hypersecretion of cholesterol, and supersaturated bile which give life to precipitating cholesterol crystals that accumulate and grow in a sluggish gallbladder. Additional factors include mucin and inflammatory changes in the gallbladder, slow intestinal motility, increased intestinal absorption of cholesterol, and altered gut microbiota. Mechanisms of disease are linked with insulin resistance, obesity, the metabolic syndrome, and type 2 diabetes. The role of nuclear receptors, signaling pathways, gut microbiota, and epigenome are being actively investigated.

SUMMARY: Ongoing research on cholesterol gallstone disease is intensively investigating several pathogenic mechanisms, associated metabolic disorders, new therapeutic approaches, and novel strategies for primary prevention, including lifestyles.