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Cholangiopathy and the biliary cast syndrome

Parry, Sally D; Muiesan, Paolo

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European Journal of Gastroenterology & Hepatology: April 2003 - Volume 15 - Issue 4 - p 341-343


Cholangiopathy is the term used to denote changes in the biliary tree in either the extrahepatic or intrahepatic biliary systems or both. The biliary cast syndrome describes the presence of casts, which may be anywhere within the biliary system causing obstruction with its resultant sequelae of biliary infection, hepatocyte damage secondary to bile stasis and ductal damage, all contributing to a cholangiopathy.

Published articles incorporating the term ‘biliary cast syndrome', obtained by searching the Pubmed database, are scant [1–3] and although biliary casts are not common they are more usually reported in orthotopic liver transplant (OLT) patients [4,5]. Two series from the 1970s, published shortly after the onset of liver transplantation programmes, first described cast formation in such patients [3,6]. Waldram et al. [6] described a series of 33 OLT patients. Post-transplant, 14 of the 22 survivors developed biliary fistulae and 12 were found to have casts in the biliary tree at laparotomy or post-mortem. In addition, two further patients without fistulae were also found to have biliary tree obstruction secondary to bile casts. Starzl et al. [3] described a series of 93 OLT patients. Post-operatively, six of the 24 cases of biliary obstruction developed casts that were so extensive that the smaller intrahepatic ducts were found to be plugged at post-mortem. Nowadays, biliary complications occur in between 6% and 34% of all liver transplant patients, typically within the first 3 months [5]. Although bile leaks and strictures are still relatively common, more complex biliary complications are still observed and these include the formation of stones, sludge or casts [2,7], which can lead to biliary obstruction. One study from Pittsburgh has looked at cholangiographic evidence of bile duct filling defects post-OLT over a 13 year period. The prevalence of bile duct filling defects was 6% and over half of these were due to sludge or casts [7].

Although the incidence of biliary complications post-OLT remains unchanged, the mortality arising from them has reduced with improvement in techniques of biliary reconstruction as well as routine biliary flushing before cold preservation, reducing the incidence of biliary sludge formation. In addition, post-OLT biliary complications are now initially managed endoscopically in the first year or so post-transplant while biliary surgery may be considered but performed later when the patients are in a better nutritional status and with lower immunosuppression levels.

Biliary cast formation in the non-transplant patient is highly unusual but has also been described in the literature [8,9]. The paper by Byrne et al., published in this issue of the journal, describes a patient with a history of traumatic head injury requiring admission to the intensive care unit. Despite endoscopic and surgical attempts at cast removal, liver transplantation was ultimately performed for biliary cast formation [8]. The other case describes an elderly lady with extensive cast formation that developed after initial recovery from emergency cholecystectomy. Despite multiple attempts at endoscopic removal, post-mortem findings confirmed the presence of diffuse bile casts and acute suppurative cholangitis [9]. Hence its rarity means that an accurate estimation of the prevalence of bile casts in non-liver transplant patients is not possible.

The exact pathogenesis of biliary casts remains uncertain but many factors have been suggested as playing an aetiological role in their formation. Theoretically, anything that increases the viscosity and/or hinders the flow of bile may precipitate cast formation. Biliary sludge, or mud, is composed of mucus, calcium bilirubinate and cholesterol crystals [10] and is a prerequisite for cast formation. It is usually recognized by characteristic echoes on ultrasonography. Starzl et al. [3] showed that biliary sludge formation was associated with defective bile duct reconstruction after liver transplantation. Damage to the bile duct mucosa may lead to precipitation of material on it and, together with infection and super-saturation of bile with cholesterol, may play a role in cast formation post-OLT [6]. Gallstones associated with haemolytic syndromes are composed predominantly of calcium bilirubinate [11] and it is feasible that haemolysis may also play a role in cast formation in certain cases. Another factor that is thought to be important in sludge development is the presence of ischaemia. One study estimated that 13% of patients post-OLT could develop an ischaemic injury unrelated to arterial thrombosis or chronic rejection [12]. Post-OLT these lesions are characterized by bile duct necroses resulting in luminal changes, biliary leakage, cast formation and hence to cholestasis. Furthermore, Sheng et al. [7] noted that the presence of sludge was associated with hepatic artery occlusion in 30% grafts, which supports the possible role of ischaemia in cast pathogenesis. Certain drugs such as ciclosporin may also play a role in cast formation by inhibiting bile secretion and promoting functional biliary stasis [13,14]. Foreign bodies such as T tubes and stents act as a nidus for stone or cast formation and a recent study has shown that bacterial attachment to biliary stents plays an important role in initiating biliary sludge formation [15]. Systemic infection post-OLT is an aggravating factor by precipitating intrahepatic cholestasis. Fungal infections, in particular, may have a more prominent role in cast formation. Unpublished experience at King's College Hospital has shown a fungal component, either Aspergillus or Candida, on microbiological analysis on all the endoscopically treated biliary casts.

In the non-liver transplant scenario, sick patients in intensive care units have been shown to develop biliary sludge frequently and rapidly [16]: in particular, abdominal surgical [17] and neurosurgical patients [16]. Fasting promotes gallbladder hypocontractility due to insufficient secretion of cholecystokinin and may, in part, explain the abdominal surgical patient group preference. Other risk factors for sludge formation include total parental nutrition [18,19], pregnancy [20] and AIDS [21]. Biliary sludge is also thought to be an underestimated cause of acute idiopathic pancreatitis [22].

There is no recommended standard management for patients who develop a cholangiopathy secondary to cast formation and each case should be viewed individually. The very presence of biliary casts means that endoscopic therapy is likely to be challenging and may very well be unsuccessful [8,9,23]. However, we would suggest that endoscopic retrograde cholangiopancreatography is a reasonable step to take prior to consideration for laparotomy as endoscopic removal has been shown previously to be effective in 25% of post-OLT patients with cast formation [24] as well as in published single cases [1,4] and with personal experience (P.M.). For casts that are difficult to extract endoscopically, nasobiliary drainage has been suggested as being helpful [5], but again, data are limited.

To summarize, biliary casts are not common but are typically seen in the post-liver transplant patient. Biliary infection, bile duct damage and ischaemia, fasting, haemolysis and abdominal surgery are all factors that may be implicated in their development. With continued improvement in techniques of graft preservation and biliary reconstruction, the development of biliary sludge and casts has become a much rarer complication following liver transplantation in the absence of an anastomotic obstruction of the common bile duct. Once diagnosed, initial management should be aimed at removal via endoscopic techniques. Biliary cast formation in the non-transplant patient remains highly unusual, but possible.


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biliary cast syndrome; biliary sludge; cholangiopathy

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