Careful examination of the pathophysiologies of uncommon diseases sometimes provides new theories and investigative approaches for related common conditions. Such is the case with the provocative study by Ohta and colleagues (11, who undertook an immunohistochemical evaluation of the distribution of apoprotein A-1 (Apo A-1) in the liver and biliary tree in patients with an uncommon condition that might best be termedprirnary cholesterol hepatolithiasis. For years it has been speculated that some patients with cholesterol hepatolithiasis form stones mainly in the bile ducts rather than through retrograde migration of gallbladder stones into the common bile duct. However, no proof of this mechanism existed. This hypothesis arose because some patients with common bile duct cholesterol lithiasis did not have concomitant gallbladder stones (2). Subsequently, several investigators in Japan reported cases of primary cholesterol hepatolithiasis (3, 4). Although cholesterol stones represent 3% to 10% of cases in surgical series of hepatolithiasis in Japan (5, 6), such cases are only rarely identified in Western countries, including the United States. Hepatolithiasis involves 3% of patients in surgical series of gallstones in Japan (6) and more than 50% of patients in series from some areas of Taiwan (71, but cholesterol hepatolithiasis has not been reported.
The identification of primary cholesterol hepatolithiasis prompts several questions: (a) What alterations of normal physiology lead to precipitation of cholesterol in the intrahepatic biliary tree? (b) What is the normal mechanism that almost always prevents precipitation of cholesterol in the intrahepatic bile ducts in patients with hepatic bile significantly supersaturated with cholesterol? (c) Why are cases of this disease now found in Japan? Japan has traditionally had a significant incidence of hepatolithiasis due to brown stones (5, 6); only in recent years have a decrease in brown stones and intrahepatic lithiasis and an increase in cholesterol stones been demonstrated (2). (d) Why haven't there been reports of this type of intrahepatic stone disease from other countries in the Far East? Is it because the Japanese diet has become more West-