Biliary lipid composition in cholesterol microlithiasis

Fracchia, M.; Pellegrino, Salvatore; Secreto, P.; Gallo, L; Masoero, G.; Pera, A; Galatola, G.

doi:10.1136/gut.48.5.702

Cited by 31 publications

(24 citation statements)

References 36 publications

(29 reference statements)

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“…There was also a significant rise in plasma total cholesterol in dogs with mobile sludge compared to control dogs. Similar results are found in human beings with biliary sludge, where cholesterol concentration of bile is higher in patients with biliary sludge than in those without them …”

Section: Discussionsupporting

confidence: 84%

“…Similar results are found in human beings with biliary sludge, where cholesterol concentration of bile is higher in patients with biliary sludge than in those without them. 4,35 The potential bias regarding the breed of each group is one of the limitations of this study. Beagles are possibly overrepresented in the control (15/24; 62.5%) and the mobile sludge groups (11/24; 45.8%), but they are the dominant breed in both groups, therefore comparison between the two groups is likely valid.…”

Section: Discussionmentioning

confidence: 95%

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Decreased Gallbladder Emptying in Dogs With Biliary Sludge or Gallbladder Mucocele

Tsukagoshi¹,

Ohno

Tsukamoto³

et al. 2011

Vet Radiology Ultrasound

102

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Biliary sludge in dogs is dismissed commonly as an incidental finding. On the other hand, gallbladder mucocele is reported increasingly in dogs and can lead to biliary obstruction or gallbladder rupture. Cholestasis is suspected to play a role in development of sludge and mucoceles, though there are no data in dogs to support this. We investigated gallbladder emptying, a key factor in biliary flow, in dogs with mobile sludge, immobile sludge, or gallbladder mucocele and in healthy controls. Gallbladder ejection fraction estimated by ultrasonography was used as the index of gallbladder emptying. The ejection fraction at 60 min after eating was significantly decreased in all three abnormal groups. Moreover, all dogs with sludge or a mucocele had gallbladder distension. These changes were the greatest in the mucocele group. Thus, biliary stasis occurs not only in dogs with gallbladder mucocele but also in dogs with biliary sludge. Cholestasis may play a role in the pathogenesis or progression of these diseases in dogs.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 95%

Decreased Gallbladder Emptying in Dogs With Biliary Sludge or Gallbladder Mucocele

Tsukagoshi¹,

Ohno

Tsukamoto³

et al. 2011

Vet Radiology Ultrasound

102

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“…Shoda et al42 demonstrated recently that the formation of cholesterol and cholesterol‐rich brown pigment stones in intrahepatic bile ducts may be caused by a decreased hepatic efflux of phospholipids because these patients showed significantly decreased levels of ABCB4 mRNA and protein levels as well as reduced phospholipid concentrations in gallbladder bile 42. Fracchia et al43 further supported this concept by demonstrating that patients with cholesterol microlithiasis display significantly decreased mean percent molar concentrations of phospholipids in duodenal bile. Interestingly, using polarizing light microscopy of hepatic cryostat sections, we observed intrahepatic crystal agglomerates in 7‐month‐old Mdr2 −/− mice (Fig.…”

Section: Discussionmentioning

confidence: 97%

Spontaneous cholecysto- and hepatolithiasis inMdr2?/? mice: A model for low phospholipid-associated cholelithiasis

et al. 2004

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Previously, we identified needle-like and filamentous, putatively "anhydrous" cholesterol crystallization in vitro at very low phospholipid concentrations in model and native biles. Our aim now was to address whether spontaneous gallstone formation occurs in Mdr2 (Abcb4) knockout mice that are characterized by phospholipid-deficient bile. Biliary phenotypes and cholesterol crystallization sequences in fresh gallbladder biles and non-fixed liver sections were determined by direct and polarizing light microscopy. The physical chemical nature and composition of crystals and stones were determined by sucrose density centrifugation and before mass and infrared spectroscopy. Gallbladder biles of Mdr2 -/-mice precipitate needle-like cholesterol crystals at 12 weeks of age on chow. After 15 weeks, more than 50% of Mdr2 -/-mice develop gallbladder stones, with female mice displaying a markedly higher gallstone-susceptibility. Although gallbladder biles of Mdr2 -/-mice contain only traces (< 1.1 mM) of phospholipid and cholesterol, they become supersaturated with cholesterol and plot in the left 2-phase zone of the ternary phase diagram, consistent with "anhydrous" cholesterol crystallization. Furthermore, more than 40% of adult female Mdr2 -/-mice show intra-and extrahepatic bile duct stones. In conclusion, spontaneous gallstone formation is a new consistent feature of the Mdr2 -/-phenotype. The Mdr2 -/-mouse is therefore a model for low phospholipid-associated cholelithiasis recently described in humans with a dysfunctional mutation in the orthologous ABCB4 gene. The mouse model supports the concept that this gene is a monogenic risk factor for cholesterol gallstones and a target for novel therapeutic strategies. (HEPATOLOGY 2004;39:117-128.)

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“…It suggests that the biliary symptoms experienced by these patients are probably caused by cholesterol crystal deposits and bile duct inflammation but not directly and exclusively related to the presence of detectable gallstones. Increased cholesterol saturation index and a defect in the hepatic transport and biliary secretion of phospholipids in patients with an intrahepatic cholesterol gallstone disease or an acute pancreatitis associated with biliary microlithiasis have been shown in another studies [3,4]. …”

Section: Clinical Descriptionmentioning

confidence: 93%

Low phospholipid associated cholelithiasis: association with mutation in the MDR3/ABCB4 gene

Rosmorduc

Poupon

2007

Orphanet J Rare Dis

149

107

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Low phospholipid-associated cholelithiasis (LPAC) is characterized by the association of ABCB4 mutations and low biliary phospholipid concentration with symptomatic and recurring cholelithiasis. This syndrome is infrequent and corresponds to a peculiar small subgroup of patients with symptomatic gallstone disease. The patients with the LPAC syndrome present typically with the following main features: age less than 40 years at onset of symptoms, recurrence of biliary symptoms after cholecystectomy, intrahepatic hyperechoic foci or sludge or microlithiasis along the biliary tree. Defect in ABCB4 function causes the production of bile with low phospholipid content, increased lithogenicity and high detergent properties leading to bile duct luminal membrane injuries and resulting in cholestasis with increased serum gamma-glutamyltransferase (GGT) activity. Intrahepatic gallstones may be evidenced by ultrasonography (US), computing tomography (CT) abdominal scan or magnetic resonance cholangiopancreatography, intrahepatic hyperechogenic foci along the biliary tree may be evidenced by US, and hepatic bile composition (phospholipids) may be determined by duodenoscopy. In all cases where the ABCB4 genotyping confirms the diagnosis of LPAC syndrome in young adults, long-term curative or prophylactic therapy with ursodeoxycholic acid (UDCA) should be initiated early to prevent the occurrence or recurrence of the syndrome and its complications. Cholecystectomy is indicated in the case of symptomatic gallstones. Biliary drainage or partial hepatectomy may be indicated in the case of symptomatic intrahepatic bile duct dilatations filled with gallstones. Patients with end-stage liver disease may be candidates for liver transplantation. Disease name and synonymsLow phospholipid associated cholelithiasis Cholelithiasis with ABCB4 gene mutation ABCB4 gene mutation-associated cholelithiasis DefinitionLow phospholipid-associated cholelithiasis (LPAC) is characterized by the association of ABCB4 mutations with symptomatic and recurring cholelithiasis in young adults (e.g. <40 years). EpidemiologyThe exact prevalence of LPAC remains unknown. The disease is more common in young adults, the usual age at the onset of the symptoms is typically lower than 40 years.

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Biliary lipid composition in cholesterol microlithiasis

Cited by 31 publications

References 36 publications

Decreased Gallbladder Emptying in Dogs With Biliary Sludge or Gallbladder Mucocele

Decreased Gallbladder Emptying in Dogs With Biliary Sludge or Gallbladder Mucocele

Spontaneous cholecysto- and hepatolithiasis inMdr2?/? mice: A model for low phospholipid-associated cholelithiasis

Low phospholipid associated cholelithiasis: association with mutation in the MDR3/ABCB4 gene

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