The highest incidence of intrahepatic stones occurs in East Asia. Within this geographic area, Taiwan has the highest incidence: such stones are found in up to 40 per cent of patients with gallstone disease. They are also common in Hong Kong, the coastal provinces of South China, Singapore, Korea, and Japan. In Western countries, intrahepatic stones are usually only found in immigrants from East Asia: they are rarely found in the indigenous population.

Calcium bilirubinate is the major component of over 90 per cent of intrahepatic stones. About 5 to 20 per cent (by weight) is cholesterol. In some countries there has been a recent trend for increasing cholesterol content, probably due to a gradual dietary change. Calcium bilirubinate is formed when bilirubin is deconjugated, liberating bilirubin which combines with Ca²⫀ in the bile. Deconjugation of bilirubin is catalysed by the enzyme &bgr;-glucuronidase, which is produced in large quantities by some species of enteric bacteria. Infection of the biliary system by enteric bacteria therefore precedes formation of intrahepatic stones.

Bacteria can arrive at the biliary system from the gut via portal blood, lymphatics, or retrogradely through the ampulla. Which of these routes is the most common portal of entry is not known. A defect in the ability of the liver to clear bacteria and infestation of bile ducts by parasites may increase susceptibility to bacterial colonization. More investigations are needed to define the aetiology and pathology of intrahepatic stones.

The most commonly cultured organisms are Gram-negative enteric bacteria: E. coli, Klebsiella, Aerobacter, and Streptococcus faecalis. More than 50 per cent of positive bile cultures yield mixed growths of up to five species of bacteria, and anaerobic organisms are present in about 30 per cent of cultures, usually mixed with aerobic organisms. Clostridia and Bacteroides are the most common anaerobes.

About 50 per cent of patients have stones in ducts of both the right and left lobes. In the remaining patients, stones are present in the left side five times more often than in the right. Stones are also present in the gallbladder or in the common bile duct in about 60 per cent of patients.

The symptoms of intrahepatic stones are fever and either right upper quadrant or epigastric pain, or both. Obstruction or strictures may occur at lobar or segmental ducts, and jaundice may therefore be absent. The intensity of symptoms varies from mild, with only minimal tenderness and fever, to severe with shock, mental confusion and multiorgan failure.

Complete blood count, liver and renal function tests, coagulation profile, and arterial blood gases should be obtained. If the biliary obstruction is lobar or segmental, the serum bilirubin level may be normal but alkaline phosphatase and glutamyl peptidase levels are invariably elevated. Elevated levels of liver parenchymal enzymes and lactic dehydrogenase are indicative of and proportional to the intensity of biliary inflammation.

On ultrasound of the liver, biliary tree, and pancreas, an experienced examiner can identify intrahepatic stones with an accuracy of 90 per cent. Ductal dilatation, abscess, and pneumobilia can also be detected by ultrasonography. The site of obstruction can only be inferred by noting the transition between a dilated and a non-dilated system; direct cholangiography by the endoscopic or transhepatic route is necessary to demonstrate the exact site of obstruction. Cholangiography should be performed in the acute stage only if urgent intervention is contemplated; otherwise it should be deferred until after full recovery.

If the diagnosis of intrahepatic stones is confirmed or strongly suspected on clinical grounds, conservative treatment should be started. The patient is fasted, fluid and electrolyte imbalances corrected by intravenous administration of fluids, and an antibiotic, usually a second or third-generation cephalosporin, is given. In about 80 per cent of the patients, cholangitis resolves with this regimen. Urgent intervention, either operative or non-operative, is required if the condition of the patient deteriorates or if there is no improvement after a reasonable length of treatment (the duration of treatment depending on the severity of the presenting symptoms). A patient admitted in shock should undergo biliary decompression if there is no obvious improvement after a few hours of treatment and resuscitation, while a patient with only mild or moderate symptoms can be safely managed conservatively for 3 to 4 days under close observation.

Thorough investigations, including repeated ultrasonography, endoscopic retrograde cholangiopancreatography, and CT, should be performed immediately after resolution of cholangitis. The entire biliary tree should be visualized by cholangiography before any definitive procedure is performed. Endoscopic retrograde cholangiopancreatography is the investigation of choice. The use of a balloon tipped contrast injection catheter with the balloon inflated at the ampullary area can enhance the visualization of partially obstructed ducts. Completely obstructed ducts may require transhepatic cholangiography for visualization. CT is most useful in determining whether an affected segment or lobe of the liver has atrophied, and in detecting distortion of the normal anatomy caused by compensating hypertrophy.

Traditionally, urgent biliary decompression involves surgery. The common duct is explored and stones in the common and hepatic ducts, which dislodge readily, are removed. A T-tube is inserted into the common duct. If the obstruction is located at the hepatic or segmental ducts, a transhepatic tube is inserted. Surgical decompression is usually successful, even in patients with high common duct or intrahepatic obstructions. Liver abscesses, if present, can also be drained.

Emergency surgical drainage carries a mortality rate of up to 20 per cent in high risk patients. In addition, because of the unstable condition of patients and lack of knowledge of the location and number of stones and strictures, the operations are seldom definitive: with few exceptions, stones are retained. Postoperative choledochoscopy has, to a great extent, alleviated this problem. The majority of retained stones can be removed, although the treatment of strictures is not usually successful. Mild strictures can be dilated with balloon catheters.

Recently, urgent endoscopic decompression has been used to treat unresponding patients with intrahepatic stones. Drainage is accomplished by introducing a nasobiliary catheter to above the level of the obstruction. A papillotomy is added if stones are present in the common duct. The advantage of endoscopic drainage is that, if successful the patients can then undergo thorough investigations. The subsequent surgery is both safer and more definitive. The disadvantage is that this approach often fails to relieve obstructions high in the common duct or in the intrahepatic ducts. An unsuccessful attempt delays operative decompression and increases the risks to an already sick patient. Identification of patients suitable for endoscopic decompression is another area deserving of further investigation.

The operative procedure to be performed is carefully planned after reviewing the results of all investigations in patients who respond to antibiotic treatment. In about 15 per cent of patients, the stones are localized to one lobe or segment of the liver, which is usually atrophied because of chronic obstruction and inflammation. These are candidates for liver resection. Patients not suitable for resection require removal of all stones and drainage of obstructed ducts. The common duct is explored first, flexible choledochoscopy is performed, and all branches of hepatic ducts are inspected. Stones are retrieved by forceps, spoons, or baskets introduced through the working channel of the choledochoscope. Most strictures are located close to the confluence of the main hepatic ducts. The choledochotomy is extended up to the confluence and the stricture is assessed to see if the planned drainage procedure can be carried out. Depending on the severity and length of strictures, drainage can be effected by dilatation, reconstruction of the strictured orifices, or by creation of bilioenteric anastomoses to dilated segmental ducts. Strictures involving the common duct are relieved by hepaticojejunostomies.

The incidence of retained stones is high in spite of meticulous inspection and removal of stones. Further removal of stones relies on choledochoscopy performed through the matured T-tube or transhepatic tube tract. The flexible choledochoscope is an indispensable instrument in the treatment of intrahepatic stones. About 80 per cent of retained intrahepatic stones and practically all retained common duct stones can be successfully removed. Strictures must be dealt with during the operation: dilatation procedures performed postoperatively through the choledochoscope are seldom effective in the longterm.

The high incidence of retained stones has contributed to the high proportion of patients who suffer recurrent symptoms (25 per cent in 5 years). As the incidence of retained stones drops, so the long-term result improves. Many new techniques have been developed to fragment and retrieve stones, both intraoperatively and postoperatively: some of these are applications of techniques used in the treatment of renal calculi. Electrohydraulic shock waves, ultrasound (applied via sonotrodes), and laser are forms of energy which have been used for stone fragmentation. Fragments are removed by basket retrieval, flushing, or ultrasound cavitation suction.

Non-operative procedures are also being developed for the treatment of intrahepatic stones. Percutaneous transhepatic cholangioscopy is a technique by which a tract is created directly to the stone-bearing ducts, and a choledochoscope is used to remove stones. The use of extracorporeal shockwave lithotripsy is also being investigated, as is dissolution using a variety of solvents.

The treatment of intrahepatic stones is undergoing a major evolution, both technically and conceptually. Each method of treatment must be evaluated not only by safety in application and effectiveness, but also by other factors, such as convenience, comfort, cost, and patient acceptance. This is influenced by information gained through public media. Surgeons should be aware of and participate in the new trends in the coming years.

Choi S, Choi TK, Wong J. Intraoperative flexible choledochoscopy for intrahepatic and extrahepatic biliary calculi. Surgery 1987; 101: 571 - 5.

Choi TK, Fok M, Lee MJR, Lui R, Wong J. Postoperative flexible choledochoscopy for residual primary intrahepatic stones. Ann Surg 1986; 203: 260 - 5.

Choi TK, Wong J, Ong GB. The surgical management of primary intrahepatic stones. Br J Surg 1982; 69: 86 - 90.

Ikeda S, et al. Emergency decompression of the bile duct in acute obstructive suppurative cholangitis by duodenoscopic cannulation: a lifesaving procedure. World J Surg 1981; 5: 587 - 93.

Maki T. Pathogenesis of calcium bilirubinate gallstone: role of E. coli, beta-glucuronidase and coagulation by inorganic ions, polyelectrolytes and agitation. Ann Surg 1966; 164: 90 - 100.

Nakayama F, et al. Hepatolithiasis in East Asia—retrospective study. Dig Dis Sci 1986; 31: 21 - 6.

Yamakawa T. Percutaneous transhepatic stone extraction technique for management of retained biliary tract stones. Prog Clin Biol Res 1984; 152: 251 - 68.