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Low phospholipid-associated cholestasis and cholelithiasis (LPAC) is a genetic disorder characterized by cholesterol gallbladder and intrahepatic stones. It is caused by a mutation of the gene ABCB4, which encodes the canalicular protein ABCB4/MDR3, a flippase that plays an essential role in the secretion of phosphatidylcholine into bile. Failure of this protein leads to secretion of bile that is poor in phospholipids and, hence, highly lithogenic, with potent detergent properties. This, in turn, leads to cholangiocyte luminal membrane injury and biliary lesions causing cholestasis. The diagnosis should be suspected when at least two of the following criteria are present: onset of symptoms before the age of 40 years; recurrence of biliary symptoms (biliary colic, jaundice, cholangitis, acute pancreatitis) after cholecystectomy; presence of echogenic foci within the liver indicative of intrahepatic stones or biliary sludge; previous episode(s) of intrahepatic cholestasis of pregnancy; and family history of gallstones in first-degree relatives. Intrahepatic stones can be demonstrated by ultrasonography with color Doppler examination, computed tomography and magnetic resonance imaging with magnetic resonance cholangiography, and the diagnosis confirmed by ABCB4 genotyping. Therapy with ursodeoxycholic acid offers prompt relief of symptoms and usually prevents complications. In some cases, however, surgery may be necessary., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

A 35-year-old woman is referred for right upper quadrant abdominal pain and fever. She had a cholecystectomy for gallstones 4 years previously. An aunt has also had a cholecystectomy. Abdominal ultrasound examination shows numerous hyperechoic foci within the liver and some "comet tail" artifacts. Because of her age (less than 40), the recurrence of biliary symptoms after cholecystectomy, her family history and the intrahepatic hyperechoic foci, the diagnosis of low phospholipid-associated cholelithiasis (LPAC) syndrome is suspected and confirmed by the demonstration of a point mutation of the ABCB4 gene. Therapy by ursodeoxycholic acid (AUDC) is started. Symptoms improve and they disappear completely within a few weeks. The cause, pathophysiology, diagnosis and treatment are reviewed.

The prevalence of cholesterol gallstones is increased in obese persons. The risk is especially high in those with the highest body mass index (relative risk 5-6). Weight loss further increases the risk of gallstones: the prevalence of new gallstones reaches 10-12% after 8-16 weeks of low-calorie diet and more than 30% within 12-18 months after gastric by-pass surgery. About one-third of the stones are symptomatic. The increased prevalence of stones is mostly due to supersaturation of bile with cholesterol, because of an increased synthesis by the liver and secretion into bile. Saturation is further increased during weight loss. It returns toward normal after weight stabilization at a lower level, allowing spontaneous stone dissolution in some cases. Identified risk factors for gallstones during weight loss are a relative loss of weight greater than 24% of initial body weight, a rate of weight loss greater than 1.5 kg per week, a very low calorie diet with no fat, a long overnight fast period and a high serum triglyceride level. Ursodeoxycholic acid decreases cholesterol saturation of bile and gallstone incidence during weight loss. Other preventive measures include a control of weight loss rate, a reduction of the length of overnight fast, and maintenance of a small amount of fat in the diet.

Hepatic and bile duct involvement are common in sickle cell disease. This article reports the case of a young woman with cholangiopathy, homozygous sickle cell disease, and protracted anemia. We suggest that sickle cell disease was directly responsible for ischemic cholangiopathy through anoxia.

The aim of this study was to prospectively evaluate endoscopic ultrasonography and microscopic examination of duodenal bile in the diagnosis of cholecystolithiasis not detected by conventional ultrasonography. Forty five consecutive patients (26 females, 19 males, mean age: 50 years) with suspected cholecystolithiasis and at least two normal transcutaneous ultrasonography examinations were included. Endoscopic ultrasonographic criteria for the diagnosis of cholecystolithiasis were the presence of stones with or without acoustic shadowing or sludge. Criteria of microscopic examination of bile were cholesterol or bilirubinate crystals or spheroliths. Thirty three patients underwent cholecystectomy and lithiasis was found in gall bladder bile in 24. Twelve patients who were not operated on and were followed up (median: 17 months), had no evidence of cholecystolithiasis. Endoscopic ultrasonography and duodenal bile examination were 96% and 67% sensitive, respectively (p < 0.03). The specificity was not different (86 and 91%, respectively). None of the 16 patients with negative results in both procedures had evidence of cholecystolithiasis. It was found that for the diagnosis of cholecystolithiasis in patients with normal conventional ultrasonography, the sensitivity of endoscopic ultrasonography is higher than that of microscopic examination of duodenal bile. If endoscopic ultrasonography and microscopic examination of duodenal bile are negative, the risk of underdiagnosing cholecystolithiasis is negligible.

Oral dissolution therapy can be proposed to patients with symptomatic gallstones, with stones less than 15 mm diameter, in any number, without calcification, within a functioning gallbladder (i.e. opacified by oral cholecystography). In particular, it may be useful in patients aged over 70, or with a high operative risk, or who refuse surgery or general anesthesia. Extracorporeal shock wave lithotripsy (followed by oral dissolution therapy) is also indicated in symptomatic gallstones, without calcification or slightly calcified in a functioning gallbladder, when stone size is between 8-10 and 30 mm and stone number lower than 3. After successful dissolution, recurrence is observed with an incidence of 5 to 10% per year during the first five years. In case of symptomatic recurrence, retreatment is indicated.

A double-blind randomized, multicenter study was carried out to determine the efficacy and safety of ursodeoxycholic acid (UDCA) at 4 doses of 2.1 to 16.2 mg X kg-1 X day-1, and chenodeoxycholic acid (CDCA) at the dose of 16.9 mg X kg-1 X day-1, in 197 patients treated for up to 1 year for radiolucent gallstones in functioning (opacified) gallbladders. There was confirmed complete dissolution in 5.9% of patients receiving UDCA at the dose of 2.1 mg X kg-1 X day-1, 18.9% in those receiving 4.2, 28.9% in those receiving 8.4, 14.6% in those receiving 16.2, and 20.0% in patients receiving CDCA. Partial (over 50%) or complete dissolution occurred in 29.4% of patients receiving 2.1 mg X kg-1 X day-1 of UDCA, 37.8% of those receiving 4.2, 55.2% in those receiving 8.4, 48.7% in those receiving 16.2, and 50.0% in patients receiving CDCA. Complete dissolution occurred significantly more frequently in small (less than 5 mm in diameter) than in large (5 to 15 and more than 15 mm) stones. There was no significant influence of treatment on serum cholesterol and triglycerides in any of the groups. Serum aminotransferases remained normal (or lower than twice the upper normal limit) in all patients treated with UDCA. Diarrhea leading to cessation of treatment occurred in 5% of patients receiving UDCA, but was significantly less frequent than in those receiving CDCA. These results confirm that, within a 1-year period, UDCA is equally effective and induces diarrhea less frequently than CDCA, with an optimal dose (8 mg X kg-1 X day-1) approximately twice lower than that of CDCA.

During cholecystectomy, gallbladder bile and gallstones were obtained from 77 patients and gallbladder bile was obtained from 39 patients free of stones (11 patients had biliary stenosis). According to their chemical composition, gallstones were classified as cholesterol (n = 46) or pigment (n = 31) stones. In patients with gallstones (a) cholesterol crystals better helped to identify cholesterol gallstones (sensitivity, 87%; specificity, 97%; positive predictive value, 97%) than did an abnormal cholesterol saturation index of bile (sensitivity, 93%; specificity, 48%; positive predictive value, 73%); (b) the presence of cholesterol crystals was significantly related to the cholesterol content of gallstones and the bile cholesterol saturation index; and (c) bilirubinate crystals, when present alone (without cholesterol crystals), were good predictors of pigment gallstones (sensitivity, 71%; specificity, 93%; positive predictive value, 88%). In the absence of stones, bilirubinate crystals were present in 9 of 28 patients without biliary stenosis (4 with alcoholic cirrhosis and 2 with alcoholic pancreatitis) and 8 of 11 patients with biliary stenosis. In the absence of stones, cholesterol crystals were present in 2 of 28 patients without biliary stenosis and in 4 of 11 patients with biliary stenosis, suggesting that bile stasis can induce cholesterol crystal formation.

Oral dissolution treatment with chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) is indicated in the case of cholesterol gallstones. However, three conditions must be satisfied for treatment to be effective: 1) the stones must be radiolucent; 2) the gallbladder must be functioning, i.e. opacified by oral cholecystography; 3) the stones must be smaller than 15 mm in diameter. Most authors consider that treatment is only justified when the stones are symptomatic. On the basis of these criteria, it has been estimated that about 20% of patients with gallstones presenting to gastroenterologists could be suitable for treatment. The mean percentage of efficacy is of the order of 50 to 60% at 18 months to 2 years. This percentage may be as high as 70-80% in the case of floating stones smaller than 1 cm. At the optimal dose (15 mg/kg/day), CDCA may induce diarrhoea and raised transaminases. Its prolonged administration can induce hepatic lesions. UDCA (7-10 mg/kg/day) generally does not have any side effect. The combination of CDCA/UDCA at the dose of 7-8 mg/kg/day of each agent may be more effective. After stopping treatment, a recurrence is observed in about 50% of cases within 5 years. Regular ultrasonographic follow-up (annually, for example) is therefore necessary to treat recurrences in time. Because of the criteria of efficacy and its adverse effects, oral dissolution treatment is only indicated in a very limited number of patients. However, it constitutes an essential complement to extracorporeal lithotripsy, which may represent its principal indication at the present time.