Gallstones

Abstract

Gallstones grow inside the gallbladder or biliary tract. These stones can be asymptomatic or symptomatic; only gallstones with symptoms or complications are defined as gallstone disease. Based on their composition, gallstones are classified into cholesterol gallstones, which represent the predominant entity, and bilirubin ('pigment') stones. Black pigment stones can be caused by chronic haemolysis; brown pigment stones typically develop in obstructed and infected bile ducts. For treatment, localization of the gallstones in the biliary tract is more relevant than composition. Overall, up to 20% of adults develop gallstones and >20% of those develop symptoms or complications. Risk factors for gallstones are female sex, age, pregnancy, physical inactivity, obesity and overnutrition. Factors involved in metabolic syndrome increase the risk of developing gallstones and form the basis of primary prevention by lifestyle changes. Common mutations in the hepatic cholesterol transporter ABCG8 confer most of the genetic risk of developing gallstones, which accounts for ∼25% of the total risk. Diagnosis is mainly based on clinical symptoms, abdominal ultrasonography and liver biochemistry tests. Symptoms often precede the onset of the three common and potentially life-threatening complications of gallstones (acute cholecystitis, acute cholangitis and biliary pancreatitis). Although our knowledge on the genetics and pathophysiology of gallstones has expanded recently, current treatment algorithms remain predominantly invasive and are based on surgery. Hence, our future efforts should focus on novel preventive strategies to overcome the onset of gallstones in at-risk patients in particular, but also in the population in general.

Cholecystectomy as a risk factor of metabolic syndrome: from epidemiologic clues to biochemical mechanisms

“…1 Factors such as physical inactivity, obesity, and overnutrition increase the risk of developing gallstones and form the basis of primary prevention by lifestyle changes. 2 Although treatment of asymptomatic gallstone patients is not routinely recommended, current treatment algorithms for symptomatic gallstone patients, by contrast, remain predominantly invasive and are based on surgery. 3 Cholecystectomy is the best and most cost-effective treatment for gallstone disease, and one of the most commonly performed operations worldwide.…”

Genetics of gallstone disease

“…3 The disease susceptibility loci were mapped by identifying the genomic regions where the distributions of marker genotypes correlate with differences in stone phenotypes in experimental crosses of inbred mouse strains. Quantitative trait locus analysis in inbred strains of mice challenged with lithogenic diets containing high concentrations of cholesterol (and cholic acid) led to the detection of many lithogenic genes to date, including the hepatobiliary cholesterol transporter Abcg5/g8.…”

“…Up to 20% of all Europeans have gallstones. 3 These differences are most likely not solely caused by the prevalence of GD but might as well be the result of different medical approaches to patients with symptomatic and mildly-symptomatic stones. Based on their chemical composition, gallstones are classified into cholesterol, black or brown bilirubin stones (pigment stones).…”

Mouse models of gallstone disease

“…Cholesterol gallstone disease is one of the most prevalent digestive diseases and affects ~12% of American adults, leading to a considerable financial and social burden in the USA [1 ▪▪ ,2 ▪▪ ,3–5]. To reduce the morbidity, mortality, and costs of healthcare associated with this disease, it is important to understand the pathophysiology of gallstones and this will facilitate the development of a novel, effective, and noninvasive therapy for patients with gallstones.…”