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The gallbladder and biliary tract in cystic fibrosis

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Abstract

Chronic liver disease is a major complication of cystic fibrosis. Its incidence and severity are variable, and diagnosis relies on a combination of clinical evaluation, biochemical testing, and radiologic assessment. Identifying patients who have early disease is critical, and the administration of ursodeoxycholic acid appears to be beneficial. The pathogenesis is incompletely understood, and factors that contribute to the variability in incidence and severity are unknown. Fortunately, only a small proportion of individuals progress to advanced liver disease; however, in this population, there is significant morbidity and impairment in quality of life. Liver transplantation can be performed successfully in patients with end-stage liver disease. Future treatments involve targeted gene therapy and activation of mutant forms of the cystic fibrosis transmembrane conductance regulator.

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References and Recommended Reading

  1. Anderson D: Cystic fibrosis of pancreas and its relation to celiac disease. Am J Dis Child 1938, 56:344–349.

    Google Scholar 

  2. Feranchak AP, Sokol RJ: Cholangiocyte biology and cystic fibrosis liver disease. Semin Liver Dis 2001, 21:471–488.

    Article  PubMed  CAS  Google Scholar 

  3. Colombo C, Battezzati PM, Podda M: Hepatobiliary disease in cystic fibrosis. Semin Liver Dis 1994, 14:259–269.

    PubMed  CAS  Google Scholar 

  4. Oppeinheimer E, Esterly J: Hepatic changes in young infants with cystic fibrosis: possible relation to focal biliary cirrhosis. J Pediatr 1975, 86:683–689.

    Article  Google Scholar 

  5. Vawter GF, Shwachman H: Cystic fibrosis in adults: an autopsy study. Pathol Annu 1979, 14:357–382.

    PubMed  Google Scholar 

  6. Scott-Jupp R, Lama M, Tanner MS: Prevalence of liver disease in cystic fibrosis. Arch Dis Child 1991, 66:698–701.

    PubMed  CAS  Google Scholar 

  7. Colombo C, Battezzati PM, Crosignani A, et al.: Liver disease in cystic fibrosis: a prospective study on incidence, risk factors, and outcome. Hepatology 2002, 36:1374–1382. This paper highlights the need for prospective evaluation of patients with predetermined measurable variables and thus accurately determines the incidence of liver disease in CF patients

    PubMed  Google Scholar 

  8. Lindblad A, Glaumann H, Strandvik B: Natural history of liver disease in cystic fibrosis. Hepatology 1999, 30:1151–1158. This paper also reports on a prospective analysis of CF patients using predetermined variables including histology.

    Article  PubMed  CAS  Google Scholar 

  9. Efrati O, Barak A, Modan-Moses D, et al.: Liver cirrhosis and portal hypertension in cystic fibrosis. Eur J Gastroenterol Hepatol 2003, 15:1073–1078.

    Article  PubMed  Google Scholar 

  10. Debray D, Lykavieris P, Gauthier F, et al.: Outcome of cystic fibrosis-associated liver cirrhosis: management of portal hypertension. J Hepatol 1999, 31:77–83.

    Article  PubMed  CAS  Google Scholar 

  11. Rovsing H, Sloth K: Micro-gallbladder and biliary calculi in mucoviscidosis. Acta Radiol Diagn (Stockh) 1973, 14:588–592.

    CAS  Google Scholar 

  12. Nagel RA, Westaby D, Javaid A, et al.: Liver disease and bile duct abnormalities in adults with cystic fibrosis. Lancet 1989, 2:1422–1425.

    Article  PubMed  CAS  Google Scholar 

  13. Gaskin KJ, Waters DL, Howman-Giles R, et al.: Liver disease and common-bile-duct stenosis in cystic fibrosis. N Engl J Med, 1988, 318:340–346.

    Article  PubMed  CAS  Google Scholar 

  14. Kerem E, Corey M, Kerem BS, et al.: The relation between genotype and phenotype in cystic fibrosis: analysis of the most common mutation (delta F508). N Engl J Med 1990, 323:1517–1522.

    Article  PubMed  CAS  Google Scholar 

  15. Knight RA: Genetics of cystic fibrosis. Br J Hosp Med 1992, 47:502–506.

    PubMed  CAS  Google Scholar 

  16. Santis G, Osborne L, Knight RA, Hodson ME: Independent genetic determinants of pancreatic and pulmonary status in cystic fibrosis. Lancet 1990, 336:1081–1084.

    Article  PubMed  CAS  Google Scholar 

  17. Davis PB, Drumm M, Konstan MW: Cystic fibrosis. Am J Respir Crit Care Med 1996, 154:1229–1256.

    PubMed  CAS  Google Scholar 

  18. De Arce M, O’Brien S, Hegarty J, et al.: Deletion delta F508 and clinical expression of cystic fibrosis-related liver disease. Clin Genet 1992, 42:271–272.

    Article  PubMed  Google Scholar 

  19. Duthie A, Doherty DG, Williams C, et al.: Genotype analysis for delta F508, G551D and R553X mutations in children and young adults with cystic fibrosis with and without chronic liver disease. Hepatology 1992, 15:660–664.

    Article  PubMed  CAS  Google Scholar 

  20. Cohn JA, Strong TV, Picciotto MR, et al.: Localization of the cystic fibrosis transmembrane conductance regulator in human bile duct epithelial cells. Gastroenterology 1993, 105:1857–1864. The first description of the localization of the CFTR to the biliary epithelium.

    PubMed  CAS  Google Scholar 

  21. Lindblad A, Hultcrantz R, Strandvik B: Bile-duct destruction and collagen deposition: a prominent ultrastructural feature of the liver in cystic fibrosis. Hepatology 1992, 16:372–381.

    Article  PubMed  CAS  Google Scholar 

  22. Duthie A, Doherty DG, Donaldson PT, et al.: The major histocompatibility complex influences the development of chronic liver disease in male children and young adults with cystic fibrosis. J Hepatol 1995, 23:532–537.

    Article  PubMed  CAS  Google Scholar 

  23. Mieli-Vergani G, Psacharopoulos HT, Nicholson AM, et al.: Immune responses to liver membrane antigens in patients with cystic fibrosis and liver disease. Arch Dis Child 1980, 55:696–701.

    PubMed  CAS  Google Scholar 

  24. Besancon F, Przewlocki G, Baro I, et al.: Interferon-gamma downregulates CFTR gene expression in epithelial cells. Am J Physiol 1994, 267:C1398-C1404.

    PubMed  CAS  Google Scholar 

  25. Donaldson PT, Farrant JM, Wilkinson ML, et al.: Dual association of HLA DR2 and DR3 with primary sclerosing cholangitis. Hepatology 1991, 13:129–133.

    PubMed  CAS  Google Scholar 

  26. Sheth S, Shea JC, Bishop MD, et al.: Increased prevalence of CFTR mutations and variants and decreased chloride secretion in primary sclerosing cholangitis. Hum Genet 2003, 113:286–292.

    Article  PubMed  Google Scholar 

  27. Flamant C, Henrion-Caude A, Boelle PY, et al.: Glutathione-Stransferase M1, M3, P1 and T1 polymorphisms and severity of lung disease in children with cystic fibrosis. Pharmacogenetics 2004, 14:295–301. This paper provides a possible explanation for the variability in the presentation and severity of CF-related liver disease and examines the possibility that polymorphisms in the GSTP1 genes expressed in human hepatic stellate and biliary epithelial cells may account for this variability.

    Article  PubMed  CAS  Google Scholar 

  28. Henrion-Caude A, Flamant C, Roussey M, et al.: Liver disease in pediatric patients with cystic fibrosis is associated with glutathione S-transferase P1 polymorphism. Hepatology 2002, 36:913–917.

    PubMed  CAS  Google Scholar 

  29. Dray-Charier N, Paul A, Scoazec JY, et al.: Expression of delta F508 cystic fibrosis transmembrane conductance regulator protein and related chloride transport properties in the gallbladder epithelium from cystic fibrosis patients. Hepatology 1999, 29:1624–1634.

    Article  PubMed  CAS  Google Scholar 

  30. van Haren EH, Hopman WP, Jansen JB, et al.: Increased plasma cholecystokinin levels and small gall bladders in adult patients with cystic fibrosis. Clin Sci (Lond) 1991, 81:85–89.

    Google Scholar 

  31. Angelico M, Gandin C, Canuzzi P, et al.: Gallstones in cystic fibrosis: a critical reappraisal. Hepatology 1991, 14:768–775.

    Article  PubMed  CAS  Google Scholar 

  32. Smith FE, Doughty IM, David TJ, et al.: Severe jaundice in two infants with cystic fibrosis. J R Soc Med 1996, 89:289P-290P.

    PubMed  CAS  Google Scholar 

  33. Valman HB, France NE, Wallis PG: Prolonged neonatal jaundice in cystic fibrosis. Arch Dis Child 1971, 46:805–809.

    PubMed  CAS  Google Scholar 

  34. Torstenson OL, Humphrey GB, Edson JR, Warwick WJ: Cystic fibrosis presenting with severe hemorrhage due to vitamin K malabsorption: a report of three cases. Pediatrics 1970, 45:857–861.

    PubMed  CAS  Google Scholar 

  35. Stern RC, Rothstein FC, Doershuk CF, Treatment and prognosis of symptomatic gallbladder disease in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr 1986, 5:35–40.

    Article  PubMed  CAS  Google Scholar 

  36. Patrick MK, Howman-Giles R, De Silva M, et al.: Common bile duct obstruction causing right upper abdominal pain in cystic fibrosis. J Pediatr 1986, 108:101–102.

    Article  PubMed  CAS  Google Scholar 

  37. Magruder MJ, Munden MM: Intrahepatic microlithiasis: another gastrointestinal complication of cystic fibrosis. J Ultrasound Med 1997, 16:763–765.

    PubMed  CAS  Google Scholar 

  38. Tanner MS, Taylor CJ: Liver disease in cystic fibrosis. Arch Dis Child 1995, 72:281–284.

    PubMed  CAS  Google Scholar 

  39. Ling SC, Wilkinson JD, Hollman AS, et al.: The evolution of liver disease in cystic fibrosis. Arch Dis Child 1999, 81:129–132.

    PubMed  CAS  Google Scholar 

  40. Gerling B, Becker M, Staab D, Schuppan D: Prediction of liver fibrosis according to serum collagen VI level in children with cystic fibrosis. N Engl J Med 1997, 336:1611–1612.

    Article  PubMed  CAS  Google Scholar 

  41. Wyatt HA, Dhawan A, Cheeseman P, et al.: Serum hyaluronic acid concentrations are increased in cystic fibrosis patients with liver disease. Arch Dis Child 2002, 86:190–193.

    Article  PubMed  CAS  Google Scholar 

  42. Williams SG, Evanson JE, Barrett N, et al.: An ultrasound scoring system for the diagnosis of liver disease in cystic fibrosis. J Hepatol 1995, 22:513–521.

    Article  PubMed  CAS  Google Scholar 

  43. Williams SM, Goodman R, Thomson A, et al.: Ultrasound evaluation of liver disease in cystic fibrosis as part of an annual assessment clinic: a 9-year review. Clin Radiol 2002, 57:365–370.

    Article  PubMed  Google Scholar 

  44. Picciotto A, Ciravegna G, Lapertosa G, Celle G: Percutaneous or laparoscopic needle biopsy in the evaluation of chronic liver disease? Am J Gastroenterol 1984, 79:567–568.

    PubMed  CAS  Google Scholar 

  45. O’Brien S, Keogan M, Casey M, et al.: Biliary complications of cystic fibrosis. Gut 1992, 33:387–391.

    PubMed  CAS  Google Scholar 

  46. Durieu I, Pellet O, Simonot L, et al.: Sclerosing cholangitis in adults with cystic fibrosis: a magnetic resonance cholangiographic prospective study. J Hepatol 1999, 30:1052–1056.

    Article  PubMed  CAS  Google Scholar 

  47. Chase HP, Long MA, Lavin MH: Cystic fibrosis and malnutrition. J Pediatr 1979, 95:337–347.

    Article  PubMed  CAS  Google Scholar 

  48. Heymans HS: Gastrointestinal dysfunction and its effects on nutrition in CF. Acta Paediatr Scand Suppl 1989, 363:74–78; discussion 78-79.

    PubMed  CAS  Google Scholar 

  49. Leuschner U, Fischer H, Kurtz W, et al.: Ursodeoxycholic acid in primary biliary cirrhosis: results of a controlled doubleblind trial. Gastroenterology 1989, 97:1268–1274.

    PubMed  CAS  Google Scholar 

  50. Beuers U, Boyer JL, Paumgartner G: Ursodeoxycholic acid in cholestasis: potential mechanisms of action and therapeutic applications. Hepatology 1998, 28:1449–1453.

    Article  PubMed  CAS  Google Scholar 

  51. Colombo C, Battezzati PM, Podda M, et al.: Ursodeoxycholic acid for liver disease associated with cystic fibrosis: a doubleblind multicenter trial. The Italian Group for the Study of Ursodeoxycholic Acid in Cystic Fibrosis. Hepatology 1996, 23:1484–1490.

    Article  PubMed  CAS  Google Scholar 

  52. O’Brien SM, Campbell GR, Burke AF, et al.: Serum bile acids and ursodeoxycholic acid treatment in cystic fibrosis-related liver disease. Eur J Gastroenterol Hepatol 1996, 8:477–483.

    PubMed  CAS  Google Scholar 

  53. Colombo C, Crosignani A, Assaisso M, et al.: Ursodeoxycholic acid therapy in cystic fibrosis-associated liver disease: a doseresponse study. Hepatology 1992, 16:924–930.

    Article  PubMed  CAS  Google Scholar 

  54. Lindblad A, Glaumann H, Strandvik B: A two-year prospective study of the effect of ursodeoxycholic acid on urinary bile acid excretion and liver morphology in cystic fibrosis-associated liver disease. Hepatology 1998, 27:166–174.

    Article  PubMed  CAS  Google Scholar 

  55. Snyder CL, Ferrell KL, Saltzman DA, et al.: Operative therapy of gallbladder disease in patients with cystic fibrosis. Am J Surg 1989, 157:557–561.

    Article  PubMed  CAS  Google Scholar 

  56. McGrath DS, Short C, Bredin CP, et al.: Laparoscopic cholecystectomy in adult cystic fibrosis. Ir J Med Sci 1997, 166:70–71.

    Article  PubMed  CAS  Google Scholar 

  57. Edelman DS: Laparoscopic cholecystectomy under continuous epidural anesthesia in patients with cystic fibrosis. Am J Dis Child 1991, 145:723–724.

    PubMed  CAS  Google Scholar 

  58. Fridell JA, Bond GJ, Mazariegos GV, et al.: Liver transplantation in children with cystic fibrosis: a long-term longitudinal review of a single center’s experience. J Pediatr Surg 2003, 38:1152–1156.

    Article  PubMed  Google Scholar 

  59. Molmenti EP, Squires RH, Nagata D, et al.: Liver transplantation for cholestasis associated with cystic fibrosis in the pediatric population. Pediatr Transplant 2003, 7:93–97.

    Article  PubMed  Google Scholar 

  60. Noble-Jamieson G, Barnes N, Jamieson N, et al.: Liver transplantation for hepatic cirrhosis in cystic fibrosis. J R Soc Med 1996, 89(Suppl 27):31–37.

    PubMed  Google Scholar 

  61. Couetil JP, Houssin DP, Soubrane O, et al.: Combined lung and liver transplantation in patients with cystic fibrosis: a 4 1/2 year experience. J Thorac Carciovasc Curg 1995, 110:1415–1422.

    Article  CAS  Google Scholar 

  62. Grubman SA, Fang SL, Mulberg AE, et al.: Correction of the cystic fibrosis defect by gene complementation in human intrahepatic biliary epithelial cell lines. Gastroenterology 1995, 108:584–592.

    Article  PubMed  CAS  Google Scholar 

  63. Yang Y, Raper SE, Cohn JA, et al.: An approach for treating the hepatobiliary disease of cystic fibrosis by somatic gene transfer. Proc Natl Acad Sci U S A 1993, 90:4601–4605.

    Article  PubMed  CAS  Google Scholar 

  64. Zabner J, Couture LA, Gregory RJ, et al.: Adenovirus-mediated gene transfer transiently corrects the chloride transport defect in nasal epithelia of patients with cystic fibrosis. Cell 1993, 75:207–216.

    Article  PubMed  CAS  Google Scholar 

  65. Grubb BR, Pickles RJ, Ye H, et al.: Inefficient gene transfer by adenovirus vector to cystic fibrosis airway epithelia of mice and humans. Nature 1994, 371:802–806.

    Article  PubMed  CAS  Google Scholar 

  66. Egan ME, Pearson M, Weiner SA, et al.: Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science 2004, 304:600–602. A cautious optimism: This paper reports the possibility of activating the F508 mutant forms of the CFTR gene as a potential strategy for treating CF with turmeric.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Harvard Medical School, Liver Transplantation, Beth Israel Deaconess Medical Center, 110 Francis Street, Suite 7, 02215, Boston, MA, USA

    Michael P. Curry MD, MRCPI & John E. Hegarty MD, FRCP

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  1. Michael P. Curry MD, MRCPI
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  2. John E. Hegarty MD, FRCP
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Curry, M.P., Hegarty, J.E. The gallbladder and biliary tract in cystic fibrosis. Curr Gastroenterol Rep 7, 147–153 (2005). https://doi.org/10.1007/s11894-005-0053-6

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