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Molecular pathogenesis of hepatolithiasis--a type of low phospholipid-associated cholelithiasis.

Hepatolithiasis is prevalent in East Asia, including Japan, but occurs much less frequently in Western countries. Hepatolithiasis appears mostly as brown pigment stones (calcium bilirubinate stones). The disease is characterized by its intractable nature and frequent recurrence, requiring multiple endoscopic or operative interventions, in distinct contrast to gallbladder cholesterol or black pigment stones. In view of the lack of information on the pathogenesis, a multidisciplinary approach has been carried out through the Hepatolithiasis Research Group organized by the Ministry of Health, Labor and Welfare of Japan. In this review, the up-to-date data on the molecular pathogenesis of hepatolithiasis with special reference to a defect in phospholipid metabolism are introduced and discussed. Furthermore, a potential medical treatment targeting hepatic phospholipid transporters is proposed as a future therapeutic option for the disease.