Caroli's disease of the liver in a renal transplant recipient
Vadakethu T. Ninan1,
Mangalathillam R. N. Nampoory,1,
Kaivilayil V. Johny2,
Ram K. Gupta1,
Imre Schmidt1,
Prasad M. Nair1 and
Jaber Al-Ali1
1 Department of Medicine, Mubarak Al-Kabeer Hospital and
2 Faculty of Medicine, Kuwait University, Kuwait
Keywords: Caroli's disease; clinical course; renal transplant
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Introduction
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Caroli's disease is a rare inherited disorder of the liver, characterized by saccular and cystic dilatation of intra-hepatic biliary ducts. Association of this abnormality with autosomal recessive polycystic kidney disease (ARPKD) has been described [1]. This abnormality may remain asymptomatic and undetected throughout life but often presents in adolescence or later with episodes of bacterial cholangitis, complicated by multiple biliary calculi. Very little is known about the clinical course of Caroli's disease in renal transplant recipients. We report here our experience with a case of Caroli's disease of the liver diagnosed in a renal transplant recipient who presented with recurrent bouts of cholangitis after renal transplantation.
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Case
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Miss FA, a 25-year-old single female had been diagnosed with ARPKD at the age of 15 years, based on clinical and ultrasonographic features. Over the subsequent years of follow up, her renal function declined progressively and at the age of 20 years she was started on maintenance haemodialysis. She underwent a live unrelated donor renal transplantation a few months later at another centre and came to our unit for follow up. Maintenance immunosuppression consisted of prednisolone 10 mg once daily, cyclosporin 70 mg twice daily, and azathioprine 50 mg once daily. During the following 2 years she had two rejection episodes which were successfully reversed with courses of i.v. methylprednisolone. Two years post-transplant she was treated for an episode of Escherichia coli septicaemia. The source of the infection was not clear. An ultrasound of the abdomen carried out at the time showed findings which were interpreted as multiple cysts in the liver. There were no symptoms localized to the liver and further investigations were not undertaken at that stage. She remained stable and asymptomatic on follow up till 5 years post-transplant when she was admitted with fever, upper abdominal pain, and vomiting. On physical examination, an enlarged tender liver was palpable. Computerized tomography (CT) of the abdomen showed dilated intra- and extra-hepatic ducts with multiple biliary calculi (Figure 1
). An endoscopic retrograde cholangiopancreatography (ERCP) was undertaken and this showed dilated common bile duct (CBD) and intra-hepatic ducts with marked saccular dilatation, involving both lobes of the liver. The CBD had three calculi and there were numerous calculi seen as filling defects in the dilated intra-hepatic ducts. These features were consistent with Caroli's disease of the liver. Endoscopic sphincterectomy was carried out and CBD calculi were extracted. The calculi in the intra-hepatic ducts could not be removed. The clinical events, laboratory results, and antibiotics administered in this admission and subsequent hospital admissions are summarized in Table 1
. In a span of about 4 months she was admitted into the hospital five times with fever. Except for an occasional transient rise of serum creatinine, the renal transplant function remained stable throughout these episodes. In the fifth episode, fever was unresponsive to treatment. Ultrasound examination and gallium scan did not reveal any localized liver abscess. Under these circumstances she was referred for a liver transplantation. An orthotopic liver transplantation from a cadaveric source was successfully carried out and she has remained well over the subsequent 4 years of follow up. After the liver transplant, the maintenance immunosuppression was changed and consisted of prednisolone 5 mg daily and tacrolimus 1 mg twice daily. Recent investigations showed her serum creatinine to be stable at 170 µmol/l, with normal liver enzymes, serum albumin, and bilirubin.

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Fig. 1. Non-enhanced CT image of the patient's liver, showing saccular dilatation of intra-hepatic biliary ducts involving both lobes of the liver. Biliary calculi, some of which are calcified, are seen as high density material in the lumen of the dilated ducts.
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Discussion
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Caroli described two forms of congenital dilatation of the intra-hepatic tree, and these were associated with renal cystic disease. One of these forms has pure ductal ectasia without significant hepatic fibrosis and is termed Caroli's disease of the liver. When ductal abnormalities are associated with periportal fibrosis the disease is called Caroli's syndrome [2]. Ductal ectasia predisposes to bile stagnation and formation of biliary calculi, which increases risk of cholangitis. The association of Caroli's disease with ARPKD has been well described. Waters et al. [3] in a study of 15 children with ARPKD found that 60% of them had associated asymptomatic Caroli's disease of the liver. Several investigations have indicated that hepatic ductal plate and renal tubular differentiation share genetic determinants, and this may explain the association between these diseases [4]. Caroli's disease usually presents as a symptomatic clinical problem in adolescence or later in life. The fact that our patient developed episodes of cholangitis only after renal transplantation raises the concern that the immunosuppressed state predisposed her to development of infection. Preventing recurrent infections in patients with Caroli's disease with prophylactic antibiotics has sometimes been possible but very often this strategy is unsuccessful [5]. Results of surgical procedures aimed at improving biliary drainage to prevent infections have also not been encouraging. Our patient had diffuse involvement of both lobes of the liver and hence localized resection of the affected area was not possible. She had recurrent episodes of cholangitis at short intervals, and fever during the fifth episode was unresponsive to antibiotics. An orthotopic liver transplant was the appropriate treatment in this situation for this patient.
Orthotopic liver transplantation has been successfully carried out as treatment in some cases of Caroli's syndrome in the non-renal transplant setting [6,7]. We did not find any previous report on the clinical course of Caroli's disease in renal transplant recipients. ARPKD can progress to end-stage renal disease, and in view of its association with Caroli's disease of the liver, it is probable that more patients like ours will be encountered in whom both a renal and liver transplant could become necessary. Renal transplant recipients who develop recurrent bouts of cholangitis should undergo investigations to detect Caroli's disease, as appropriate therapy can lead to a good outcome.
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Notes
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Correspondence and offprint requests to: Dr M. R. N. Nampoory, PO Box 1427, Hawally, Code No. 32015, Kuwait. Email: nampoory{at}hotmail.com 
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References
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Sans M, Rimola A, Navasa M et al. Liver transplantation in patients with Caroli's disease and recurrent cholangitis. Transplant Intl1997; 10: 241242
Received for publication: 10. 5.01
Accepted in revised form: 15. 1.02