Cystic fibrosis: Hepatobiliary disease
- Daniel H Leung, MD
Daniel H Leung, MD
- Assistant Professor of Pediatrics
- Baylor College of Medicine
- Drucy Borowitz, MD
Drucy Borowitz, MD
- Department of Pediatrics
- State University of New York at Buffalo
- Section Editors
- George B Mallory, MD
George B Mallory, MD
- Section Editor — Pediatric Pulmonology
- Associate Professor of Pediatrics
- Baylor College of Medicine
- Elizabeth B Rand, MD
Elizabeth B Rand, MD
- Section Editor — Pediatric Hepatology
- Professor of Pediatrics
- University of Pennsylvania School of Medicine
Cystic fibrosis-related liver disease (CFLD) is becoming increasingly recognized due to early diagnosis of cystic fibrosis (CF), improved life expectancy, and more vigilant screening and monitoring by CF providers. Patients with severe CFLD usually present during childhood, and the disease tends to progress rapidly. Milder forms of CFLD can be difficult to diagnose because patients may remain asymptomatic until late in the disease process, and currently available screening tests correlate poorly with disease severity. Early identification of CFLD permits anticipation and treatment of its 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:
Subscribers log in hereLiterature review current through: Jul 2017. | This topic last updated: Oct 12, 2015.References
- Bartlett JR, Friedman KJ, Ling SC, et al. Genetic modifiers of liver disease in cystic fibrosis. JAMA 2009; 302:1076.
- Gelfond D, Borowitz D. Gastrointestinal complications of cystic fibrosis. Clin Gastroenterol Hepatol 2013; 11:333.
- 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.
- 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.
- Lamireau T, Monnereau S, Martin S, et al. Epidemiology of liver disease in cystic fibrosis: a longitudinal study. J Hepatol 2004; 41:920.
- Williams SG, Westaby D, Tanner MS, Mowat AP. Liver and biliary problems in cystic fibrosis. Br Med Bull 1992; 48:877.
- Oppenheimer EH, Esterly JR. Hepatic changes in young infants with cystic fibrosis: possible relation to focal biliary cirrhosis. J Pediatr 1975; 86:683.
- Vawter GF, Shwachman H. Cystic fibrosis in adults: an autopsy study. Pathol Annu 1979; 14 Pt 2:357.
- 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).
- 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.
- Corbett K, Kelleher S, Rowland M, et al. Cystic fibrosis-associated liver disease: a population-based study. J Pediatr 2004; 145:327.
- Wilschanski M, Rivlin J, Cohen S, et al. Clinical and genetic risk factors for cystic fibrosis-related liver disease. Pediatrics 1999; 103:52.
- Rowland M, Gallagher CG, O'Laoide R, et al. Outcome in cystic fibrosis liver disease. Am J Gastroenterol 2011; 106:104.
- Chamnan P, Shine BS, Haworth CS, et al. Diabetes as a determinant of mortality in cystic fibrosis. Diabetes Care 2010; 33:311.
- 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.
- Desai CS, Gruessner A, Habib S, et al. Survival of cystic fibrosis patients undergoing liver and liver-lung transplantations. Transplant Proc 2013; 45:290.
- 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.
- 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.
- 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.
- Colombo C, Battezzati PM. Hepatobiliary manifestations of cystic fibrosis. Eur J Gastroenterol Hepatol 1996; 8:748.
- 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.
- Greenholz SK, Krishnadasan B, Marr C, Cannon R. Biliary obstruction in infants with cystic fibrosis requiring Kasai portoenterostomy. J Pediatr Surg 1997; 32:175.
- Lykavieris P, Bernard O, Hadchouel M. Neonatal cholestasis as the presenting feature in cystic fibrosis. Arch Dis Child 1996; 75:67.
- Shapira R, Hadzic N, Francavilla R, et al. Retrospective review of cystic fibrosis presenting as infantile liver disease. Arch Dis Child 1999; 81:125.
- 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.
- 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.
- Treem WR, Stanley CA. Massive hepatomegaly, steatosis, and secondary plasma carnitine deficiency in an infant with cystic fibrosis. Pediatrics 1989; 83:993.
- 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.
- 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.
- 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.
- 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.
- 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).
- Colombo C. Liver disease in cystic fibrosis. Curr Opin Pulm Med 2007; 13:529.
- 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.
- Cheng K, Ashby D, Smyth RL. Ursodeoxycholic acid for cystic fibrosis-related liver disease. Cochrane Database Syst Rev 2014; :CD000222.
- 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.
- 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.
- 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.
- 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.
- Lindor KD, Kowdley KV, Luketic VA, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology 2009; 50:808.
- 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.
- Rudic JS, Poropat G, Krstic MN, et al. Ursodeoxycholic acid for primary biliary cirrhosis. Cochrane Database Syst Rev 2012; 12:CD000551.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Yi SG, Burroughs SG, Loebe M, et al. Combined lung and liver transplantation: analysis of a single-center experience. Liver Transpl 2014; 20:46.
- 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.
- 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.
- 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.
- 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.
- EPIDEMIOLOGY AND NATURAL HISTORY
- CLINICAL MANIFESTATIONS
- Progressive CFLD
- Other manifestations of liver disease
- - Neonatal cholestasis
- - Hepatic steatosis
- Further evaluation
- Risk reduction
- Ursodeoxycholic acid
- Management of specific complications
- - Portal hypertension
- - Hepatopulmonary syndrome
- - Portopulmonary hypertension
- - Liver failure
- Liver transplantation
- GALLBLADDER DISEASE
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS