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.

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Figure 1: Classification of gallstones.
Figure 2: Global prevalence of gallstones.
Figure 3: Cholesterol metabolism in the hepatocyte.
Figure 4: Aetiological factors involved in the formation of cholesterol gallstones and brown pigment gallstones.
Figure 5: Abdominal transcutaneous ultrasonography.
Figure 6: Endoscopic retrograde cholangiography showing simultaneous bile duct and gallbladder stones.
Figure 7: Diagnostic and therapeutic management for suspected common bile duct stones.
Figure 8: Endoscopic retrograde cholangiography for bile duct obstruction by a prepapillary stone.
Figure 9: Intraoperative endoscopic retrograde cholangiography.
Figure 10: Future perspectives for the treatment of gallstones based on personalized risk.


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This work was supported, in part, by the European Association for the Study of the Liver, by grants from Medica Sur Clinic and Foundation (to N.M.-S.), the Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT, grant 1130303 to J.-F.M.), the Italian Agency of Drugs (AIFA, grant MRAR08P011 to P.P.) and research grants DK101793 and DK106249 (to D.Q.-H.W.), both from the NIH (US Public Health Service). The authors thank C. S. Stokes and A. Arslanow (Homburg, Saarland, Germany) for superb bibliographic management.

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Introduction (F.L.); Epidemiology (J.-F.M. and F.L.); Mechanisms/pathophysiology (D.Q.-H.W. and N.M.-S.); Diagnosis, screening and prevention (K.J.v.E. and P.P.); Management (K.G., K.J.v.E., C.J.v.L., C.W.K. and F.L.); Quality of life (K.G.); Outlook (F.L.); Overview of Primer (F.L. and K.G.).

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Correspondence to Frank Lammert or Kurinchi Gurusamy.

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Lammert, F., Gurusamy, K., Ko, C. et al. Gallstones. Nat Rev Dis Primers 2, 16024 (2016).

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