Skip to main content

Advertisement

SpringerLink
Log in

Gastrointestinal Manifestations of Cystic Fibrosis

  • Review
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Gastrointestinal symptoms of cystic fibrosis are the most important non-pulmonary manifestations of this genetic illness. Pancreatic manifestations include acute and chronic pancreatitis as well as pancreas insufficiency resulting in malnutrition. Complications in the gastrointestinal lumen are diverse and include distal intestinal obstruction syndrome (DIOS), meconium ileus, intussusception, and constipation; biliary tract complications include focal biliary cirrhosis and cholangiectasis. The common pathophysiology is the inspissation of secretions in the hollow structures of the gastrointestinal tract. Improved survival of CF patients mandates that the adult gastroenterologist be aware of the presentation and treatment of pancreatic, luminal, and hepatobiliary CF complications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Gabriel SE, Brigman KN, Koller BH, et al. Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model. Science. 1994;266:107–109.

    Article  CAS  PubMed  Google Scholar 

  2. Wilschanski M, Durie PR. Patterns of GI disease in adulthood associated with mutations in the CFTR gene. Gut. 2007;56:1153–1163.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med. 2005;352:1992–2001.

    Article  CAS  PubMed  Google Scholar 

  4. O’Sullivan BP, Freedman SD. Cystic fibrosis. Lancet. 2009;373:1891–1904.

    Article  PubMed  Google Scholar 

  5. Blackman SM, Deering-Brose R, McWilliams R, et al. Relative contribution of genetic and nongenetic modifiers to intestinal obstruction in cystic fibrosis. Gastroenterology. 2006;131:1030–1039.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Kopelman H, Durie P, Gaskin K, et al. Pancreatic fluid secretion and protein hyperconcentration in cystic fibrosis. N Engl J Med. 1985;312:329–334.

    Article  CAS  PubMed  Google Scholar 

  7. Shwachman H, Lebenthal E, Khaw KT. Recurrent acute pancreatitis in patients with cystic fibrosis with normal pancreatic enzymes. Pediatrics. 1975;55:86–95.

    CAS  PubMed  Google Scholar 

  8. De Boeck K, Weren M, Proesmans M, et al. Pancreatitis among patients with cystic fibrosis: correlation with pancreatic status and genotype. Pediatrics. 2005;115:e463–e469.

    Article  PubMed  Google Scholar 

  9. King LJ, Scurr ED, Murugan N, et al. Hepatobiliary and pancreatic manifestations of cystic fibrosis: MR imaging appearances. Radiographics. 2000;20:767–777.

    Article  CAS  PubMed  Google Scholar 

  10. Sharer N, Schwarz M, Malone G, et al. Mutations of the cystic fibrosis gene in patients with chronic pancreatitis. N Engl J Med. 1998;339:645–652.

    Article  CAS  PubMed  Google Scholar 

  11. Waters DL, Dorney SF, Gaskin KJ, et al. Pancreatic function in infants identified as having cystic fibrosis in a neonatal screening program. N Engl J Med. 1990;322:303–308.

    Article  CAS  PubMed  Google Scholar 

  12. Proesmans M, De Boeck K. Omeprazole, a proton pump inhibitor, improves residual steatorrhoea in cystic fibrosis patients treated with high dose pancreatic enzymes. Eur J Pediatr. 2003;162:760–763.

    Article  CAS  PubMed  Google Scholar 

  13. Dodge JA, Turck D. Cystic fibrosis: nutritional consequences and management. Best Pract Res Clin Gastroenterol. 2006;20:531–546.

    Article  CAS  PubMed  Google Scholar 

  14. Agrons GA, Corse WR, Markowitz RI, et al. Gastrointestinal manifestations of cystic fibrosis: radiologic-pathologic correlation. Radiographics. 1996;16:871–893.

    Article  CAS  PubMed  Google Scholar 

  15. Liong SY, Awad D, Jones AM, et al. The adult cystic fibrosis patient with abdominal pain: what the radiologist needs to know. Clin Radiol. 2011;66:132–139.

    Article  CAS  PubMed  Google Scholar 

  16. Chaudry G, Navarro OM, Levine DS, et al. Abdominal manifestations of cystic fibrosis in children. Pediatr Radiol. 2006;36:233–240.

    Article  PubMed  Google Scholar 

  17. Andersen D. Cystic fibrosis of the pancreas and its relation to celiac disease: a clinical and pathologic study. Am J Dis Chil. 1938;56:344–399.

    Article  Google Scholar 

  18. Matel JL, Milla CE. Nutrition in cystic fibrosis. Semin Respir Crit Care Med. 2009;30:579–586.

    Article  PubMed  Google Scholar 

  19. Mousa HM, Woodley FW. Gastroesophageal reflux in cystic fibrosis: current understandings of mechanisms and management. Curr Gastroenterol Rep. 2012;14:226–235.

    Article  PubMed  Google Scholar 

  20. Cucchiara S, Santamaria F, Andreotti MR, et al. Mechanisms of gastro-oesophageal reflux in cystic fibrosis. Arch Dis Child. 1991;66:617–622.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Orenstein SR, Orenstein DM. Gastroesophageal reflux and respiratory disease in children. J Pediatr. 1988;112:847–858.

    Article  CAS  PubMed  Google Scholar 

  22. Eggermont E, Deboeck K. Small-intestinal abnormalities in cystic fibrosis patients. Eur J Pediatr. 1991;150:824–828.

    Article  CAS  PubMed  Google Scholar 

  23. Constantine S, Au VW, Slavotinek JP. Abdominal manifestations of cystic fibrosis in adults: a review. Australas Radiol. 2004;48:450–458.

    Article  CAS  PubMed  Google Scholar 

  24. Grossman H, Berdon WE, Baker DH. Gastrointestinal findings in cystic fibrosis. Am J Roentgenol Radium Ther Nucl Med. 1966;97:227–238.

    Article  CAS  PubMed  Google Scholar 

  25. Abramson SJ, Baker DH, Amodio JB, et al. Gastrointestinal manifestations of cystic fibrosis. Semin Roentgenol. 1987;22:97–113.

    Article  CAS  PubMed  Google Scholar 

  26. Robertson MB, Choe KA, Joseph PM. Review of the abdominal manifestations of cystic fibrosis in the adult patient. Radiographics. 2006;26:679–690.

    Article  PubMed  Google Scholar 

  27. Phelan MS, Fine DR, Zentlermunro PL, et al. Radiographic abnormalities of the duodenum in cystic fibrosis. Clin Radiol. 1983;34:573–577.

    Article  CAS  PubMed  Google Scholar 

  28. Ziegler MM. Meconium ileus. Curr Probl Surg. 1994;31:U731–U777.

    Article  Google Scholar 

  29. Karimi A, Gorter RR, Sleeboom C, et al. Issues in the management of simple and complex meconium ileus. Pediatr Surg Int. 2011;27:963–968.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Gorter RR, Karimi A, Sleeboom C, et al. Clinical and genetic characteristics of meconium ileus in newborns with and without cystic fibrosis. J Pediatr Gastroenterol Nutr. 2010;50:569–572.

    CAS  PubMed  Google Scholar 

  31. Fakhoury K, Durie PR, Levison H, et al. Meconium ileus in the absence of cystic fibrosis. Arch Dis Child. 1992;67:1204–1206.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Wyllie R. Gastrointestinal manifestations of cystic fibrosis. Clin Pediatr. 1999;38:735–738.

    Article  CAS  Google Scholar 

  33. Casaccia G, Trucchi A, Nahom A, et al. The impact of cystic fibrosis on neonatal intestinal obstruction: the need for prenatal/neonatal screening. Pediatr Surg Int. 2003;19:75–78.

    CAS  PubMed  Google Scholar 

  34. Lang I, Daneman A, Cutz E, et al. Abdominal calcification in cystic fibrosis with meconium ileus: radiologic-pathologic correlation. Pediatr Radiol. 1997;27:523–527.

    Article  CAS  PubMed  Google Scholar 

  35. Delpin CA, Czyrko C, Ziegler MM, et al. Management and survival of meconium ileus—A 30-year review. Ann Surg. 1992;215:179–185.

    Article  CAS  Google Scholar 

  36. Colombo C, Ellemunter H, Houwen R, et al. Guidelines for the diagnosis and management of distal intestinal obstruction syndrome in cystic fibrosis patients. J Cyst Fibros. 2011;10:S24–S28.

    Article  PubMed  Google Scholar 

  37. Dray X, Bienvenu T, Desmazes-Dufeu N, et al. Distal intestinal obstruction syndrome in adults with cystic fibrosis. Clin Gastroenterol Hepatol. 2004;2:498–503.

    Article  PubMed  Google Scholar 

  38. Houwen RH, van der Doef HP, Sermet I, et al. Defining DIOS and constipation in cystic fibrosis with a multicentre study on the incidence, characteristics, and treatment of DIOS. J Pediatr Gastroenterol Nutr. 2010;50:38–42.

    Article  PubMed  Google Scholar 

  39. Brown NJ, Read NW, Richardson A, et al. Characteristics of lipid substances activating the ileal brake in the rat. Gut. 1990;31:1126–1129.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. van der Doef HP, Kokke FT, van der Ent CK, et al. Intestinal obstruction syndromes in cystic fibrosis: meconium ileus, distal. Curr Gastroenterol Rep. 2011;13:265–270.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Stern RC, Izant RJ, Boat TF, et al. Treatment and prognosis of rectal prolapse in cystic-fibrosis. Gastroenterology. 1982;82:707–710.

    CAS  PubMed  Google Scholar 

  42. Siafakas C, Vottler TP, Andersen JM. Rectal prolapse in pediatrics. Clin Pediatr. 1999;38:63–72.

    Article  CAS  Google Scholar 

  43. Nash EF, Stephenson A, Helm EJ, et al. Intussusception in adults with cystic fibrosis: a case series with review of the literature. Dig Dis Sci. 2011;56:3695–3700.

    Article  PubMed  Google Scholar 

  44. Munck A, Belarbi N, de Lagausie P, et al. Ultrasonography detects appendicular mucocele in cystic fibrosis patients suffering recurrent abdominal pain. Pediatrics. 2000;105:921.

    Article  CAS  PubMed  Google Scholar 

  45. Coughlin JP, Gauderer MWL, Stern RC, et al. The spectrum of appendiceal disease in cystic fibrosis. J Pediatr Surg. 1990;25:835–839.

    Article  CAS  PubMed  Google Scholar 

  46. Lardenoye SW, Puylaert JB, Smit MJ, et al. Appendix in children with cystic fibrosis: US features. Radiology. 2004;232:187–189.

    Article  PubMed  Google Scholar 

  47. Chaun H. Colonic disorders in adult cystic fibrosis. Can J Gastroenterol. 2001;15:586–590.

    CAS  PubMed  Google Scholar 

  48. Smyth RL, Vanvelzen D, Smyth AR, et al. Strictures of ascending colon in cystic fibrosis and high-strength pancreatic-enzymes. Lancet. 1994;343:85–86.

    Article  CAS  PubMed  Google Scholar 

  49. Smyth RL, Ashby D, Ohea U, et al. Fibrosing colonopathy in cystic fibrosis—results of a case-control study. Lancet. 1995;346:1247–1251.

    Article  CAS  PubMed  Google Scholar 

  50. Moss RL, Musemeche CA, Feddersen RM. Progressive pan-colonic fibrosis secondary to oral administration of pancreatic enzymes. Pediatr Surg Int. 1998;13:168–170.

    Article  CAS  PubMed  Google Scholar 

  51. Schneider ARJ, Klueber S, Posselt HG, et al. Application of the glucose hydrogen breath test for the detection of bacterial overgrowth in patients with cystic fibrosis–a reliable method? Dig Dis Sci. 2009;54:1730–1735.

    Article  CAS  PubMed  Google Scholar 

  52. Neglia JP, FitzSimmons SC, Maisonneuve P, et al. The risk of cancer among patients with cystic fibrosis. Cystic fibrosis and cancer study group. N Engl J Med. 1995;332:494–499.

    Article  CAS  PubMed  Google Scholar 

  53. Meyer KC, Francois ML, Thomas HK, et al. Colon cancer in lung transplant recipients with CF: increased risk and results of screening. J Cyst Fibros. 2011;10:366–369.

    Article  PubMed  Google Scholar 

  54. Feranchak AP. Hepatobiliary complications of cystic fibrosis. Curr Gastroenterol Rep. 2004;6:231–239.

    Article  PubMed  Google Scholar 

  55. Sokol RJ, Durie PR. Cystic Fibrosis Fdn Hepatobiliary Dis C. Recommendations for management of liver and biliary tract disease in cystic fibrosis. J Pediatr Gastroenterol Nutr. 1999;28:S1–S13.

    Article  PubMed  Google Scholar 

  56. Colombo C. Liver disease in cystic fibrosis. Curr Opin Pulm Med. 2007;13:529–536.

    Article  PubMed  Google Scholar 

  57. 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.

    CAS  PubMed  Google Scholar 

  58. Kochar R, Fallon MB. Pulmonary diseases and the liver. Clin Liver Dis. 2011;15:21.

  59. Herrmann U, Dockter G, Lammert F. Cystic fibrosis-associated liver disease. Best Pract Res Clin Gastroenterol. 2010;24:585–592.

    Article  CAS  PubMed  Google Scholar 

  60. Lewindon PJ, Pereira TN, Hoskins AC, et al. The role of hepatic stellate cells and transforming growth factor-beta(1) in cystic fibrosis liver disease. Am J Pathol. 2002;160:1705–1715.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Lindblad A, Glaumann H, Strandvik B. Natural history of liver disease in cystic fibrosis. Hepatology. 1999;30:1151–1158.

    Article  CAS  PubMed  Google Scholar 

  62. 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.

    Article  PubMed  Google Scholar 

  63. Bartlett JR, Friedman KJ, Ling SC, et al. Genetic modifiers of liver disease in cystic fibrosis. J Am Med Assoc. 2009;302:1076–1083.

    Article  CAS  Google Scholar 

  64. 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  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  66. Colombo C, Battezzati PM, Podda M, et al. Ursodeoxycholic acid for liver disease associated with cystic fibrosis: a double-mind multicenter trial. Hepatology. 1996;23:1484–1490.

    Article  CAS  PubMed  Google Scholar 

  67. Cheng K, Ashby D, Smyth RL. Ursodeoxycholic acid for cystic fibrosis-related liver disease. Cochrane Database Syst Rev. 2012;10:CD000222.

  68. Imam MH, Sinakos E, Gossard AA, et al. High-dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis. Aliment Pharmacol Ther. 2011;34:1185–1192.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Lindor KD, Kowdley KV, Luketic VA, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009;50:808–814.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Lu BR, Esquivel CO. A review of abdominal organ transplantation in cystic fibrosis. Pediatr Transpl. 2010;14:954–960.

    Article  Google Scholar 

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

    Article  Google Scholar 

  72. Enriquez G, Lucaya J, Allende E, et al. Intrahepatic biliary stone in children. Pediatr Radiol. 1992;22:283–286.

    Article  CAS  PubMed  Google Scholar 

  73. Gaskin KJ, Waters DLM, Howmangiles R, et al. Liver disease and common-bile-duct stenosis in cystic fibrosis. N Engl J Med. 1988;318:340–346.

    Article  CAS  PubMed  Google Scholar 

  74. Perdue DG, Cass OW, Milla C, et al. Hepatolithiasis and Cholangiocarcinoma in cystic fibrosis: a case series and review of the literature. Dig Dis Sci. 2007;52:2638–2642.

    Article  PubMed  Google Scholar 

  75. Bass S, Connon JJ, Ho CS. Biliary tree in cystic fibrosis: biliary tract abnormalities in cystic fibrosis demonstrated by endoscopic retrograde cholangiography. Gastroenterology. 1983;84:1592–1596.

    CAS  PubMed  Google Scholar 

  76. Baldwin TL, Schutz SM, Owens G, et al. Successful endoscopic therapy of cholangitis associated with intrahepatic cholangiectasis in adult cystic fibrosis. Gastrointest Endosc. 1999;49:249–251.

    Article  CAS  PubMed  Google Scholar 

  77. Lo CM, Fan ST, Wong J. The changing epidemiology of recurrent pyogenic cholangitis. Hong Kong Med J. 1997;3:302–304.

    PubMed  Google Scholar 

  78. Ong GB. A study of recurrent pyogenic cholangitis. Arch Surg. 1962;84:199–225.

    Article  CAS  PubMed  Google Scholar 

  79. Wasmuth HE, Keppeler H, Herrmann U, et al. Coinheritance of Gilbert syndrome-associated UGT1A1 mutation increases gallstone risk in cystic fibrosis. Hepatology. 2006;43:738–741.

    Article  CAS  PubMed  Google Scholar 

  80. Karlas T, Neuschulz M, Oltmanns A, et al. Non-invasive evaluation of cystic fibrosis related liver disease in adults with ARFI, transient elastography and different fibrosis scores. Plos One. 2012;7:8.

    Article  Google Scholar 

  81. Treem WR, Stanley CA. Massive hepatomegaly, steatosis, and secondary plasma carnitine deficiency in an infant with cystic fibrosis. Pediatrics. 1989;83:993–997.

    CAS  PubMed  Google Scholar 

  82. Aldamiz-Echevarria L, Prieto J, Andrade F, et al. Persistence of essential fatty acid deficiency in cystic fibrosis despite nutritional therapy. Pediatr Res. 2009;66:585–589.

    Article  CAS  PubMed  Google Scholar 

  83. Freedman SD, Shea JC, Blanco PG, et al. Fatty acids in cystic fibrosis. Curr Opin Pulm Med. 2000;6:530–532.

    Article  CAS  PubMed  Google Scholar 

  84. Colombo C, Bertolini E, Assaisso ML, et al. Failure of ursodeoxycholic acid to dissolve radiolucent gallstones in patients with cystic fibrosis. Acta Paediatr. 1993;82:562–565.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  86. Roy CC, Weber AM, Morin CL, et al. Abnormal biliary lipid composition in cystic fibrosis: effect of pancreatic enzymes. N Engl J Med. 1977;297:1301–1305.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Liver Diseases, Los Angeles County Hospital, Keck School of Medicine, The University of Southern California, D & T Building Room B4H100, 1983 Marengo St, Los Angeles, CA, 90033-1370, USA

    Thomas Kelly & James Buxbaum

Authors
  1. Thomas Kelly
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James Buxbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James Buxbaum.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kelly, T., Buxbaum, J. Gastrointestinal Manifestations of Cystic Fibrosis. Dig Dis Sci 60, 1903–1913 (2015). https://doi.org/10.1007/s10620-015-3546-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-015-3546-7

Keywords

Search

Navigation