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Cystic fibrosis: Hepatobiliary disease

Authors
Daniel H Leung, MD
Michael Narkewicz, MD
Section Editors
George B Mallory, MD
Elizabeth B Rand, MD
Deputy Editor
Alison G Hoppin, MD

INTRODUCTION

Liver involvement in cystic fibrosis (CF) is common, occurring in 30 to 50 percent of individuals with CF. CF-related liver disease (CFLD) is a broad term that has been used to define a spectrum of liver involvement in CF. The recognition of CFLD is increasing due to early diagnosis of CF, improved life expectancy, and greater awareness of CFLD leading to screening and monitoring for CFLD. The most significant form of CFLD is cirrhosis with or without portal hypertension. Patients with CF cirrhosis present almost exclusively during childhood, with portal hypertension and associated complications [1]. It is unclear if milder forms of CFLD can identify individuals who will progress to advanced CFLD, and thus available screening tests have targeted nonspecific markers of liver involvement. Early identification of advanced CFLD (prior to the development of complications of portal hypertension) allows prospective monitoring for and treatment of complications, which include malnutrition, variceal bleeding due to portal hypertension, and occasionally liver failure. Other hepatobiliary complications of CF include cholelithiasis (gallstones), cholecystitis, and microgallbladder.

The clinical manifestations, diagnosis, and management of CFLD will be discussed in this topic review, and associated disorders of the gallbladder will be discussed briefly. Other topic reviews relevant to the management of a patient with CF and hepatobiliary disease include:

(See "Cystic fibrosis: Overview of gastrointestinal disease".)

(See "Cystic fibrosis-related diabetes mellitus".)

(See "Cystic fibrosis: Clinical manifestations and diagnosis".)

                          
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Literature review current through: Oct 2017. | This topic last updated: Oct 23, 2017.
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References
Top
  1. Stonebraker JR, Ooi CY, Pace RG, et al. Features of Severe Liver Disease With Portal Hypertension in Patients With Cystic Fibrosis. Clin Gastroenterol Hepatol 2016; 14:1207.
  2. Bartlett JR, Friedman KJ, Ling SC, et al. Genetic modifiers of liver disease in cystic fibrosis. JAMA 2009; 302:1076.
  3. Debray D, Kelly D, Houwen R, et al. Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease. J Cyst Fibros 2011; 10 Suppl 2:S29.
  4. National Institutes of Health/Cystic Fibrosis Foundation Clinical Research Workshop, 2009. Available at: http://rarediseases.info.nih.gov/files/cystic%20fibrosis%20%28abstract%20book%29%20client%20review.pdf (Accessed on February 24, 2015).
  5. van de Peppel IP, Bertolini A, Jonker JW, et al. Diagnosis, follow-up and treatment of cystic fibrosis-related liver disease. Curr Opin Pulm Med 2017; 23:562.
  6. Flass T, Narkewicz MR. Cirrhosis and other liver disease in cystic fibrosis. J Cyst Fibros 2013; 12:116.
  7. Gelfond D, Borowitz D. Gastrointestinal complications of cystic fibrosis. Clin Gastroenterol Hepatol 2013; 11:333.
  8. Woodruff SA, Sontag MK, Accurso FJ, et al. Prevalence of elevated liver enzymes in children with cystic fibrosis diagnosed by newborn screen. J Cyst Fibros 2017; 16:139.
  9. 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.
  10. Lamireau T, Monnereau S, Martin S, et al. Epidemiology of liver disease in cystic fibrosis: a longitudinal study. J Hepatol 2004; 41:920.
  11. Mayer-Hamblett N, Kloster M, Ramsey BW, et al. Incidence and clinical significance of elevated liver function tests in cystic fibrosis clinical trials. Contemp Clin Trials 2013; 34:232.
  12. Bodewes FA, van der Doef HP, Houwen RH, Verkade HJ. Increase of Serum γ-Glutamyltransferase Associated With Development of Cirrhotic Cystic Fibrosis Liver Disease. J Pediatr Gastroenterol Nutr 2015; 61:113.
  13. Leung DH, Ye W, Molleston JP, et al. Baseline Ultrasound and Clinical Correlates in Children with Cystic Fibrosis. J Pediatr 2015; 167:862.
  14. Lenaerts C, Lapierre C, Patriquin H, et al. Surveillance for cystic fibrosis-associated hepatobiliary disease: early ultrasound changes and predisposing factors. J Pediatr 2003; 143:343.
  15. Williams SG, Westaby D, Tanner MS, Mowat AP. Liver and biliary problems in cystic fibrosis. Br Med Bull 1992; 48:877.
  16. Oppenheimer EH, Esterly JR. Hepatic changes in young infants with cystic fibrosis: possible relation to focal biliary cirrhosis. J Pediatr 1975; 86:683.
  17. Vawter GF, Shwachman H. Cystic fibrosis in adults: an autopsy study. Pathol Annu 1979; 14 Pt 2:357.
  18. Hillaire S, Cazals-Hatem D, Bruno O, et al. Liver transplantation in adult cystic fibrosis: Clinical, imaging, and pathological evidence of obliterative portal venopathy. Liver Transpl 2017; 23:1342.
  19. Witters P, Libbrecht L, Roskams T, et al. Liver disease in cystic fibrosis presents as non-cirrhotic portal hypertension. J Cyst Fibros 2017; 16:e11.
  20. Cystic Fibrosis Foundation Patient Registry, Annual data report, 2012. Available at: http://www.cff.org/UploadedFiles/research/ClinicalResearch/PatientRegistryReport/2012-CFF-Patient-Registry.pdf (Accessed on November 05, 2014).
  21. Ye W, Narkewicz MR, Leung DH, et al. Variceal Hemorrhage and Adverse Liver Outcomes in Patients With Cystic Fibrosis Cirrhosis. J Pediatr Gastroenterol Nutr 2017.
  22. Rowland M, Gallagher CG, O'Laoide R, et al. Outcome in cystic fibrosis liver disease. Am J Gastroenterol 2011; 106:104.
  23. Chamnan P, Shine BS, Haworth CS, et al. Diabetes as a determinant of mortality in cystic fibrosis. Diabetes Care 2010; 33:311.
  24. Melzi ML, Kelly DA, Colombo C, et al. Liver transplant in cystic fibrosis: a poll among European centers. A study from the European Liver Transplant Registry. Transpl Int 2006; 19:726.
  25. Desai CS, Gruessner A, Habib S, et al. Survival of cystic fibrosis patients undergoing liver and liver-lung transplantations. Transplant Proc 2013; 45:290.
  26. Leung DH, Yimlamai D. The intestinal microbiome and paediatric liver disease. Lancet Gastroenterol Hepatol 2017; 2:446.
  27. Flass T, Tong S, Frank DN, et al. Intestinal lesions are associated with altered intestinal microbiome and are more frequent in children and young adults with cystic fibrosis and cirrhosis. PLoS One 2015; 10:e0116967.
  28. Sokol RJ, Durie PR. Recommendations for management of liver and biliary tract disease in cystic fibrosis. Cystic Fibrosis Foundation Hepatobiliary Disease Consensus Group. J Pediatr Gastroenterol Nutr 1999; 28 Suppl 1:S1.
  29. McKone EF, Emerson SS, Edwards KL, Aitken ML. Effect of genotype on phenotype and mortality in cystic fibrosis: a retrospective cohort study. Lancet 2003; 361:1671.
  30. Aldámiz-Echevarría L, Prieto JA, Andrade F, et al. Persistence of essential fatty acid deficiency in cystic fibrosis despite nutritional therapy. Pediatr Res 2009; 66:585.
  31. 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.
  32. Buxbaum J, Nguyen N, Kulkarni S, et al. Multidisciplinary Treatment of Cystic Fibrosis-Related Recurrent Pyogenic Cholangitis (CF-RPC). Dig Dis Sci 2015; 60:1801.
  33. Colombo C, Battezzati PM. Hepatobiliary manifestations of cystic fibrosis. Eur J Gastroenterol Hepatol 1996; 8:748.
  34. 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.
  35. Greenholz SK, Krishnadasan B, Marr C, Cannon R. Biliary obstruction in infants with cystic fibrosis requiring Kasai portoenterostomy. J Pediatr Surg 1997; 32:175.
  36. Lykavieris P, Bernard O, Hadchouel M. Neonatal cholestasis as the presenting feature in cystic fibrosis. Arch Dis Child 1996; 75:67.
  37. Leeuwen L, Magoffin AK, Fitzgerald DA, et al. Cholestasis and meconium ileus in infants with cystic fibrosis and their clinical outcomes. Arch Dis Child 2014; 99:443.
  38. Shapira R, Hadzic N, Francavilla R, et al. Retrospective review of cystic fibrosis presenting as infantile liver disease. Arch Dis Child 1999; 81:125.
  39. Akata D, Akhan O, Ozcelik U, et al. Hepatobiliary manifestations of cystic fibrosis in children: correlation of CT and US findings. Eur J Radiol 2002; 41:26.
  40. Patriquin H, Lenaerts C, Smith L, et al. Liver disease in children with cystic fibrosis: US-biochemical comparison in 195 patients. Radiology 1999; 211:229.
  41. Treem WR, Stanley CA. Massive hepatomegaly, steatosis, and secondary plasma carnitine deficiency in an infant with cystic fibrosis. Pediatrics 1989; 83:993.
  42. Hultcrantz R, Mengarelli S, Strandvik B. Morphological findings in the liver of children with cystic fibrosis: a light and electron microscopical study. Hepatology 1986; 6:881.
  43. 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.
  44. Reeder SB, Cruite I, Hamilton G, Sirlin CB. Quantitative assessment of liver fat with magnetic resonance imaging and spectroscopy. J Magn Reson Imaging 2011; 34:729.
  45. Klotter V, Gunchick C, Siemers E, et al. Assessment of pathologic increase in liver stiffness enables earlier diagnosis of CFLD: Results from a prospective longitudinal cohort study. PLoS One 2017; 12:e0178784.
  46. Aqul A, Jonas MM, Harney S, et al. Correlation of Transient Elastography With Severity of Cystic Fibrosis-related Liver Disease. J Pediatr Gastroenterol Nutr 2017; 64:505.
  47. Koh C, Sakiani S, Surana P, et al. Adult-onset cystic fibrosis liver disease: Diagnosis and characterization of an underappreciated entity. Hepatology 2017; 66:591.
  48. Lawson EE, Grand RJ, Neff RK, Cohen LF. Clinical estimation of liver span in infants and children. Am J Dis Child 1978; 132:474.
  49. Colombo C. Liver disease in cystic fibrosis. Curr Opin Pulm Med 2007; 13:529.
  50. Poupon R. Ursodeoxycholic acid and bile-acid mimetics as therapeutic agents for cholestatic liver diseases: an overview of their mechanisms of action. Clin Res Hepatol Gastroenterol 2012; 36 Suppl 1:S3.
  51. Cheng K, Ashby D, Smyth RL. Ursodeoxycholic acid for cystic fibrosis-related liver disease. Cochrane Database Syst Rev 2017; 9:CD000222.
  52. Nousia-Arvanitakis S, Fotoulaki M, Economou H, et al. Long-term prospective study of the effect of ursodeoxycholic acid on cystic fibrosis-related liver disease. J Clin Gastroenterol 2001; 32:324.
  53. Colombo C, Battezzati PM, Podda M, et al. Ursodeoxycholic acid for liver disease associated with cystic fibrosis: a double-blind multicenter trial. The Italian Group for the Study of Ursodeoxycholic Acid in Cystic Fibrosis. Hepatology 1996; 23:1484.
  54. Kappler M, Espach C, Schweiger-Kabesch A, et al. Ursodeoxycholic acid therapy in cystic fibrosis liver disease--a retrospective long-term follow-up case-control study. Aliment Pharmacol Ther 2012; 36:266.
  55. Siano M, De Gregorio F, Boggia B, et al. Ursodeoxycholic acid treatment in patients with cystic fibrosis at risk for liver disease. Dig Liver Dis 2010; 42:428.
  56. Lindor KD, Kowdley KV, Luketic VA, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology 2009; 50:808.
  57. Papastergiou V, Tsochatzis EA, Rodriguez-Peralvarez M, et al. Biochemical criteria at 1 year are not robust indicators of response to ursodeoxycholic acid in early primary biliary cirrhosis: results from a 29-year cohort study. Aliment Pharmacol Ther 2013; 38:1354.
  58. Rudic JS, Poropat G, Krstic MN, et al. Ursodeoxycholic acid for primary biliary cirrhosis. Cochrane Database Syst Rev 2012; 12:CD000551.
  59. Shi J, Wu C, Lin Y, et al. Long-term effects of mid-dose ursodeoxycholic acid in primary biliary cirrhosis: a meta-analysis of randomized controlled trials. Am J Gastroenterol 2006; 101:1529.
  60. Guarino MP, Cocca S, Altomare A, et al. Ursodeoxycholic acid therapy in gallbladder disease, a story not yet completed. World J Gastroenterol 2013; 19:5029.
  61. Shneider BL, Bosch J, de Franchis R, et al. Portal hypertension in children: expert pediatric opinion on the report of the Baveno v Consensus Workshop on Methodology of Diagnosis and Therapy in Portal Hypertension. Pediatr Transplant 2012; 16:426.
  62. Bloom AI, Verstandig A. SCVIR 2002 Film Panel case 2: TIPS for bleeding varices in cystic fibrosis and liver cirrhosis. J Vasc Interv Radiol 2002; 13:533.
  63. Pozler O, Krajina A, Vanicek H, et al. Transjugular intrahepatic portosystemic shunt in five children with cystic fibrosis: long-term results. Hepatogastroenterology 2003; 50:1111.
  64. Robberecht E, Van Biervliet S, Vanrentergem K, Kerremans I. Outcome of total splenectomy with portosystemic shunt for massive splenomegaly and variceal bleeding in cystic fibrosis. J Pediatr Surg 2006; 41:1561.
  65. Miller MR, Sokol RJ, Narkewicz MR, Sontag MK. Pulmonary function in individuals who underwent liver transplantation: from the US cystic fibrosis foundation registry. Liver Transpl 2012; 18:585.
  66. Usatin DJ, Perito ER, Posselt AM, Rosenthal P. Under Utilization of Pancreas Transplants in Cystic Fibrosis Recipients in the United Network Organ Sharing (UNOS) Data 1987-2014. Am J Transplant 2016; 16:1620.
  67. Bandsma RH, Bozic MA, Fridell JA, et al. Simultaneous liver-pancreas transplantation for cystic fibrosis-related liver disease: a multicenter experience. J Cyst Fibros 2014; 13:471.
  68. Faro A, Shepherd R, Huddleston CB, et al. Lower incidence of bronchiolitis obliterans in pediatric liver-lung transplant recipients with cystic fibrosis. Transplantation 2007; 83:1435.
  69. Yi SG, Burroughs SG, Loebe M, et al. Combined lung and liver transplantation: analysis of a single-center experience. Liver Transpl 2014; 20:46.
  70. Arnon R, Annunziato RA, Miloh T, et al. Liver and combined lung and liver transplantation for cystic fibrosis: analysis of the UNOS database. Pediatr Transplant 2011; 15:254.
  71. Harring TR, Nguyen NT, Liu H, et al. Liver transplantation in cystic fibrosis: a report from Baylor College of Medicine and the Texas Children's Hospital. Pediatr Transplant 2013; 17:271.
  72. 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.
  73. Dietrich CF, Chichakli M, Hirche TO, et al. Sonographic findings of the hepatobiliary-pancreatic system in adult patients with cystic fibrosis. J Ultrasound Med 2002; 21:409.
  74. Lavelle LP, McEvoy SH, Ni Mhurchu E, et al. Cystic Fibrosis below the Diaphragm: Abdominal Findings in Adult Patients. Radiographics 2015; 35:680.