The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts, above the hilar confluence of the hepatic ducts. The disease is more prevalent in Asia, mainly owing to socioeconomic and dietary factors, as well as the prevalence of biliary parasites. In the last century, owing to migration, its global incidence has increased. The main pathophysiological mechanisms involve cholangitis, bile infection and biliary strictures, creating a self-sustaining cycle that perpetuates the disease, frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of "recurrent pyogenic cholangitis". Furthermore, long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma. Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment. The management of symptomatic patients and those with complications can be complex, and relies upon a multidisciplinary team of hepatologists, endoscopists, interventional radiologists and hepatobiliary surgeons, with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications. This comprehensive review provides insight on various aspects of hepatolithiasis, with a focus on epidemiology, new evidence on pathophysiology, most important clinical aspects, different classification systems and contemporary management.

Gastrointestinal symptoms of cystic fibrosis are the most important non-pulmonary manifestations of this genetic illness. Pancreatic manifestations include acute and chronic pancreatitis as well as pancreas insufficiency resulting in malnutrition. Complications in the gastrointestinal lumen are diverse and include distal intestinal obstruction syndrome (DIOS), meconium ileus, intussusception, and constipation; biliary tract complications include focal biliary cirrhosis and cholangiectasis. The common pathophysiology is the inspissation of secretions in the hollow structures of the gastrointestinal tract. Improved survival of CF patients mandates that the adult gastroenterologist be aware of the presentation and treatment of pancreatic, luminal, and hepatobiliary CF complications.

Hepatolithiasis after hepatic portoenterostomy for biliary atresia has been paid little attention, with only 22 reported cases.

Fifteen patients underwent living-related liver transplantation for biliary atresia after hepatic portoenterostomy in our hospital between 1998 and 2004. The resected livers were examined for the existence and location of hepatolithiasis, composition of the calculi, and bacterial infection of bile. The relation between a history of cholangitis and the presence of hepatolithiasis was analyzed.

Intrahepatic calculi were found in 8 (53%) of 15 patients. The calculi consisted of almost 100% calcium bilirubinate. Calculi were found in bile lakes in 8 patients. Bacteria were present in the bile in 8 (53%) of the 15 patients. Of the 8 patients, 7 (88%) had a history of ascending cholangitis.

Hepatolithiasis occurs after hepatic portoenterostomy for biliary atresia more frequently than previously thought. Bile stasis and possibly bile infection are the main causes of calculi formation.

To describe in vitro CT features of intrahepatic stones and to correlate CT attenuation with chemical composition.

Of the patients who underwent choledochoscopic intrahepatic stone removal between 1998 and 2001, 54 patients with stones larger than 3 mm were enrolled in this study. In each case, a chemical compositional analysis was performed to determine calcium, cholesterol, total bilirubin, and inorganic phosphorus compositions. The three largest stones obtained from each patient were imaged by CT. CT attenuation numbers were measured in the center images of each stone by drawing free-hand region of interest (ROI). The measured CT attenuation numbers were correlated with their chemical composition. Also, CT attenuation numbers of stones were compared with that of the liver on non-contrast CT (50-70 HU).

Stone size ranged from 3.1 to 10.5 mm (mean +/- S.D.: 6.0 +/- 1.4). The CT attenuation numbers (HU) of stones ranged from 36.4 to 410.19 (mean +/- S.D.: 94.6 +/- 49.9). CT numbers of stones were below 70 HU in 11 patients (20.4%), and below 90 HU in 33 patients (59.3%). The chemical analysis data of the stones were as follows: calcium (0.5-6.5 wt.%; mean +/- S.D., 2.6 +/- 1.4), total bilirubin (0.45-24.4 wt.%; 13.1 +/- 6.2), cholesterol (5.4-73.9 wt.%; 29.3 +/- 17.4), phosphorus (0.1-1.2 wt.%; 0.6 +/- 0.3), and non-soluble residue (17.6-85.4 wt.%; 57.0 +/- 22.6). There was a weak but significant correlation between calcium composition and CT attenuation (r = 0.38, P < 0.01) and no significant correlation between other chemical compositions and the CT attenuation (cholesterol, r = 0.01, P > 0.01; total bilirubin, r = 0.05, P > 0.01; phosphorus, r = 0.01, P > 0.01).

On non-contrast CT, intrahepatic stones would not be hyperattenuating with respect to liver parenchyma in about one fifth of patients. The CT attenuation of stones correlates with calcium and does not correlate with any other chemical composition.

The result of hepatic portoenterostomy for biliary atresia (BA) has improved, but there are some patients who experience worsened liver function in the long term after one decrease in jaundice owing to portoenterostomy. However, the cause of the liver dysfunction in the long term has not been clearly ascertained.

Five patients (5 to 28 years of age) with BA underwent liver transplantation (LT) because of liver dysfunction after successful portoenterostomy. To clarify the cause of liver dysfunction occurring in the long term, the authors performed a cholangiogram, hepatic venogram, and macroscopic/microscopic examination of the liver just after LT.

(1) Macroscopically, the liver could be divided into 3 areas, the hypertrophic, atrophic, and intermediate, with findings between those of the hypertrophic and atrophic areas. (2) The divided areas clearly corresponded to the liver segments. Segment IV was the hypertrophic area in all patients, but segments VI and VII were the atrophic areas in 4 of the 5 patients. (3) Based on the cholangiographic and microscopic findings, the hypertrophic area had near-normal structure with bile ducts. The atrophic area had severe fibrosis and contained only a few bile ducts in the intralobular spaces of liver.

It seems that segmental bile drainage must have been established by hepatic portoenterostomy in some patients and that some postoperative patients might have worsened liver function in the long-term follow-up period accompanied with progression of fibrosis and impaired bile drainage. These pathologic changes occur in each liver segment.

The incidence of intrahepatic cholelithiasis and cholangitis has not yet been well studied postoperatively in patients with choledochal cysts.

One hundred three patients with choledochal cysts had operative cholangiography, underwent standard excision of a choledochal cyst with Roux-en-Y hepatico-jejunal anastomosis, and were at a mean follow-up of 12 1/2 years. The incidence of intrahepatic bile duct stones was analyzed according to the 3 morphologic types of intrahepatic bile duct observed at initial operative cholangiography: type 1, no dilatation of the intrahepatic bile ducts; type 2, dilatation of the intrahepatic bile ducts but without any downstream stenosis; and type 3, dilatation of the intrahepatic bile ducts associated with downstream stenosis. Initially, there was no evidence of intrahepatic bile duct stones in any of the 103 patients.

Among 50 type 1 patients, intrahepatic cholelithiasis developed in only 1 patient (2%). Among 43 type 2 patients, 1 patient (2%) had intrahepatic cholelithiasis, and 2 (5%) had postoperative cholangitis. Among 10 type 3 patients, 4 (40%) had intrahepatic cholelithiasis (P <.01), and 3 (30%) had postoperative cholangitis. Time intervals between the initial surgery and the first identification of intrahepatic stones ranged from 3 to 22 years.

One of the major causes of formation of intrahepatic cholelithiasis has been clarified; patients with intrahepatic biliary dilatation with downstream stenosis can get intrahepatic bile duct stones long after excision of a choledochal cyst.

Hepatic calcification was found in an anicteric infant with biliary atresia after hepatic portoenterostomy. When she was 2 years of age, ultrasonography detected an echogenic structure with acoustic shadowing. Computerized tomography located it at the proximal portion of Segment 6 in the right lobe. Although both techniques failed to exhibit dilatation of the peripheral bile ducts, we believe intrahepatic cholelithiasis provides the most likely diagnosis. Although seven cases with biliary atresia were reported to have this complication, all of them were icteric when the diagnosis was confirmed. The patient should be carefully followed up since the succeeding stones may cause jaundice by obstructing the main duct.