- Frederick J Suchy, MD, FAASLD
Frederick J Suchy, MD, FAASLD
- Chief Research Officer, Director
- The Children’s Hospital Research Institute
- Professor of Pediatrics, Associate Dean for Child Health Research
- University of Colorado School of Medicine
- Section Editors
- Sanjiv Chopra, MD, MACP
Sanjiv Chopra, MD, MACP
- Editor-in-Chief — Gastroenterology and Hepatology
- Section Editor — General Hepatology; Gallbladder and Biliary Tract Disease
- Professor of Medicine
- Harvard Medical School
- Senior Consultant in Hepatology
- James Tullis Firm Chief
- Beth Israel Deaconess Medical Center
- Elizabeth B Rand, MD
Elizabeth B Rand, MD
- Section Editor — Pediatric Hepatology
- Professor of Pediatrics
- University of Pennsylvania School of Medicine
Caroli disease is a congenital disorder characterized by multifocal, segmental dilatation of large intrahepatic bile ducts [1,2]. The condition is usually associated with renal cystic disease of varying severity. Caroli initially described two variants, which has led to some confusion in terminology.
●Caroli disease is the less common form and is characterized by bile ductular ectasia without other apparent hepatic abnormalities.
●The more common variant is Caroli syndrome in which bile duct dilatation is associated with congenital hepatic fibrosis .
Caroli disease and syndrome have been described in the same family. Most cases are transmitted in an autosomal recessive fashion and are associated with autosomal recessive polycystic kidney disease (ARPKD). There have been rare cases occurring with autosomal dominant polycystic kidney disease .
The molecular pathogenesis of Caroli disease and syndrome is incompletely understood. The gene underlying autosomal recessive polycystic kidney disease (ARPKD) had been mapped to chromosome 6 (6p21-p12). The affected gene (called PKHD1 for polycystic kidney and hepatic disease 1) encodes for a large protein (4074 amino acids), which has been called fibrocystin to reflect the main structural abnormalities in liver and kidney . The protein shares structural features with the hepatocyte growth factor receptor, localizes to cilia, and appears to belong to a superfamily of proteins that are involved in the regulation of cell proliferation, and of cellular adhesion and repulsion [6,7]. It does not share any homology with the proteins responsible for autosomal dominant polycystic kidney disease (ADPKD). PKHD1 is expressed primarily in the kidneys with lower levels in liver, pancreas, and lungs, a pattern consistent with phenotype of the disease, which primarily affects the liver and kidneys. The genetic basis for the difference in Caroli disease and syndrome has not been defined.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Summerfield JA, Nagafuchi Y, Sherlock S, et al. Hepatobiliary fibropolycystic diseases. A clinical and histological review of 51 patients. J Hepatol 1986; 2:141.
- Murray-Lyon IM, Shilkin KB, Laws JW, et al. Non-obstructive dilatation of the intrahepatic biliary tree with cholangitis. Q J Med 1972; 41:477.
- Desmet VJ. What is congenital hepatic fibrosis? Histopathology 1992; 20:465.
- Torra R, Badenas C, Darnell A, et al. Autosomal dominant polycystic kidney disease with anticipation and Caroli's disease associated with a PKD1 mutation. Rapid communication. Kidney Int 1997; 52:33.
- Ward CJ, Hogan MC, Rossetti S, et al. The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein. Nat Genet 2002; 30:259.
- Onuchic LF, Furu L, Nagasawa Y, et al. PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats. Am J Hum Genet 2002; 70:1305.
- Gunay-Aygun M. Liver and kidney disease in ciliopathies. Am J Med Genet C Semin Med Genet 2009; 151C:296.
- Calvet JP, Grantham JJ. The genetics and physiology of polycystic kidney disease. Semin Nephrol 2001; 21:107.
- Newby LJ, Streets AJ, Zhao Y, et al. Identification, characterization, and localization of a novel kidney polycystin-1-polycystin-2 complex. J Biol Chem 2002; 277:20763.
- Hildebrandt F. Genetic kidney diseases. Lancet 2010; 375:1287.
- Desmet VJ. Congenital diseases of intrahepatic bile ducts: variations on the theme "ductal plate malformation". Hepatology 1992; 16:1069.
- D'Agata ID, Jonas MM, Perez-Atayde AR, Guay-Woodford LM. Combined cystic disease of the liver and kidney. Semin Liver Dis 1994; 14:215.
- Desmet VJ. Ludwig symposium on biliary disorders--part I. Pathogenesis of ductal plate abnormalities. Mayo Clin Proc 1998; 73:80.
- Veigel MC, Prescott-Focht J, Rodriguez MG, et al. Fibropolycystic liver disease in children. Pediatr Radiol 2009; 39:317.
- Jung G, Benz-Bohm G, Kugel H, et al. MR cholangiography in children with autosomal recessive polycystic kidney disease. Pediatr Radiol 1999; 29:463.
- Asselah T, Ernst O, Sergent G, et al. Caroli's disease: a magnetic resonance cholangiopancreatography diagnosis. Am J Gastroenterol 1998; 93:109.
- Hussain SZ, Bloom DA, Tolia V. Caroli's disease diagnosed in a child by MRCP. Clin Imaging 2000; 24:289.
- Lefere M, Thijs M, De Hertogh G, et al. Caroli disease: review of eight cases with emphasis on magnetic resonance imaging features. Eur J Gastroenterol Hepatol 2011; 23:578.
- Taylor AC, Palmer KR. Caroli's disease. Eur J Gastroenterol Hepatol 1998; 10:105.
- Dağli U, Atalay F, Saşmaz N, et al. Caroli's disease: 1977-1995 experiences. Eur J Gastroenterol Hepatol 1998; 10:109.
- Caroli-Bosc FX, Demarquay JF, Conio M, et al. The role of therapeutic endoscopy associated with extracorporeal shock-wave lithotripsy and bile acid treatment in the management of Caroli's disease. Endoscopy 1998; 30:559.
- Okugawa T, Tsuyuguchi T, K C S, et al. Peroral cholangioscopic treatment of hepatolithiasis: Long-term results. Gastrointest Endosc 2002; 56:366.
- Ros E, Navarro S, Bru C, et al. Ursodeoxycholic acid treatment of primary hepatolithiasis in Caroli's syndrome. Lancet 1993; 342:404.
- Moreno González E, Gómez Sanz R, Hidalgo Pascual M, et al. Surgical treatment of congenital dilatation of the biliary system. Hepatogastroenterology 1993; 40:134.
- Ammori BJ, Jenkins BL, Lim PC, et al. Surgical strategy for cystic diseases of the liver in a western hepatobiliary center. World J Surg 2002; 26:462.
- Kassahun WT, Kahn T, Wittekind C, et al. Caroli's disease: liver resection and liver transplantation. Experience in 33 patients. Surgery 2005; 138:888.
- Mabrut JY, Partensky C, Jaeck D, et al. Congenital intrahepatic bile duct dilatation is a potentially curable disease: long-term results of a multi-institutional study. Ann Surg 2007; 246:236.
- Ulrich F, Pratschke J, Pascher A, et al. Long-term outcome of liver resection and transplantation for Caroli disease and syndrome. Ann Surg 2008; 247:357.
- Mabrut JY, Kianmanesh R, Nuzzo G, et al. Surgical management of congenital intrahepatic bile duct dilatation, Caroli's disease and syndrome: long-term results of the French Association of Surgery Multicenter Study. Ann Surg 2013; 258:713.
- Waechter FL, Sampaio JA, Pinto RD, et al. The role of liver transplantation in patients with Caroli's disease. Hepatogastroenterology 2001; 48:672.
- Habib S, Shakil O, Couto OF, et al. Caroli's disease and orthotopic liver transplantation. Liver Transpl 2006; 12:416.
- Harring TR, Nguyen NT, Liu H, et al. Caroli disease patients have excellent survival after liver transplant. J Surg Res 2012; 177:365.
- Fevery J, Tanghe W, Kerremans R, et al. Congenital dilatation of the intrahepatic bile ducts associated with the development of amyloidosis. Gut 1972; 13:604.