Hepatolithiasis-epidemiology and pathogenesis update

Hepatolithiasis or intrahepatic calculi are prevalent in East Asia, including Japan, but occurs much less frequently in Western countries. Hepatolithiasis appears mostly as brown pigment stones (calcium bilirubinate stones) but contain more cholesterol in composition. The disease is characterized by its intractable nature and frequent recurrence, requiring multiple operative interventions, in distinct contrast to gallbladder cholesterol or black pigment stones. Moreover, the most unfavorable complication of the disease is an intrahepatic cholangiocarcinoma. 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 and Welfare of Japan. In this review, the up-to-date data on the epidemiology and pathogenesis of hepatolithiasis are introduced and discussed. Furthermore, potential medical treatments targeting pathogenetic molecules, which may be important for the etiological process of gallstone formation, are introduced as future therapeutic options for the disease.