Background Cystic fibrosis-related liver disease (CFLD) is present in up to 30% of cystic fibrosis patients and can result in progressive liver failure. Diagnosis of CFLD is challenging. Non-invasive methods for staging of liver fibrosis display an interesting diagnostic approach for CFLD detection. Aim We evaluated transient elastography (TE), acoustic radiation force impulse imaging (ARFI), and fibrosis indices for CFLD detection. Methods TE and ARFI were performed in 55 adult CF patients. In addition, AST/Platelets-Ratio-Index (APRI), and Forns' score were calculated. Healthy probands and patients with alcoholic liver cirrhosis served as controls. Results Fourteen CF patients met CFLD criteria, six had liver cirrhosis. Elastography acquisition was successful in >89% of cases. Non-cirrhotic CFLD individuals showed elastography values similar to CF patients without liver involvement. Cases with liver cirrhosis differed significantly from other CFLD patients (ARFI: 1.49 vs. 1.13 m/s; p = 0.031; TE: 7.95 vs. 4.16 kPa; p = 0.020) and had significantly lower results than individuals with alcoholic liver cirrhosis (ARFI: 1.49 vs. 2.99 m/s; p = 0.002). APRI showed the best diagnostic performance for CFLD detection (AUROC 0.815; sensitivity 85.7%, specificity 70.7%). Conclusions ARFI, TE, and laboratory based fibrosis indices correlate with each other and reliably detect CFLD related liver cirrhosis in adult CF patients. CF specific cut-off values for cirrhosis in adults are lower than in alcoholic cirrhosis.
References
[1]
Debray D, Kelly D, Houwen R, Strandvik B, Colombo C (2011) Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease. J Cyst Fibros 10: S29–36.
[2]
Colombo C, Battezzati PM (2004) Liver involvement in cystic fibrosis: primary organ damage or innocent bystander? J Hepatol 41: 1041–1044.
[3]
Moyer K, Balistreri W (2009) Hepatobiliary disease in patients with cystic fibrosis. Curr Opin Gastroenterol 2009 25: 272–278.
[4]
Williams SG, Evanson JE, Barrett N, Hodson ME, Boultbee JE, et al. (1995) An ultrasound scoring system for the diagnosis of liver disease in cystic fibrosis. J Hepatol 22: 513–521.
[5]
Williams SM, Goodman R, Thomson A, McHugh K, Lindsell DRM (2002) Ultrasound evaluation of liver disease in cystic fibrosis as part of an annual assessment clinic: a 9-year review. Clin Radiol 57: 365–370.
[6]
Sokol RJ, Durie PR (1999) Recommendations for management of liver and biliary tract disease in cystic fibrosis. Cystic Fibrosis Foundation Hepatobiliary Disease Consensus Group. J Pediatr Gastroenterol Nutr 28: S1–13.
[7]
Colombo C, Battezzati PM, Crosignani A, Morabito A, Costantini D, et al. (2002) Liver disease in cystic fibrosis: A prospective study on incidence, risk factors, and outcome. Hepatology 36: 1374–1382.
[8]
Mueller-Abt PR, Frawley KJ, Greer RM, Lewindon PJ (2008) Comparison of ultrasound and biopsy findings in children with cystic fibrosis related liver disease. J Cyst Fibros 7: 215–221.
[9]
Lewindon PJ, Shepherd RW, Walsh MJ, Greer RM, Wiliamson R, et al. (2011) Importance of hepatic fibrosis in cystic fibrosis and the predictive value of liver biopsy. Hepatology 53: 193–201.
[10]
Sandrin L, Fourquet B, Hasquenoph J, Yon S, Fournier C, et al. (2003) Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol 29: 1705–1713.
[11]
Friedrich-Rust M, Wunder K, Kriener S, Sotoudeh F, Richter S, et al. (2009) Liver fibrosis in viral hepatitis: noninvasive assessment with acoustic radiation force impulse imaging versus transient elastography. Radiology 252: 595–604.
[12]
Menten R, Leonard A, Clapuyt P, Vincke P, Nicolae A, et al. (2010) Transient elastography in patients with cystic fibrosis. Pediatr Radiol 40: 1231–1235.
[13]
Witters P, Boeck Kde, Dupont L, Proesmans M, Vermeulen F, et al. (2009) Non-invasive liver elastography (Fibroscan) for detection of cystic fibrosis-associated liver disease. J Cyst Fibros 8: 392–399.
[14]
Malbrunot-Wagner AC, Bridoux L, Nousbaum JB, Riou C, Dirou A, et al. (2011) Transient elastography and portal hypertension in pediatric patients with cystic fibrosis Transient elastography and cystic fibrosis. J Cyst Fibros 10: 338–342.
[15]
Manco M, Lo Zupone C, Latini A, Lucidi V, Monti L (2011) Noninvasive assessment of cystic fibrosis-associated liver disease with acoustic radiation force impulse imaging. Hepatology 53: 1779–1780.
[16]
Karlas T, Pfrepper C, Wiegand J, Wittekind C, Neuschulz M, et al. (2011) Acoustic radiation force impulse imaging (ARFI) for non-invasive detection of liver fibrosis: examination standards and evaluation of interlobe differences in healthy subjects and chronic liver disease. Scand J Gastroenterol 46: 1458–1467.
[17]
Bota S, Sporea I, Sirli R, Popescu A, D？nil？ M, et al. (2011) Factors that influence the correlation of acoustic radiation force impulse (ARFI) elastography with liver fibrosis. Med Ultrason 13: 135–140.
[18]
Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, et al. (2011) Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology 53: 726–736.
[19]
Forns X, Ampurdanès S, Llovet JM, Aponte J, Quinto L, et al. (2002) Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology 36: 986–992.
[20]
DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44: 837–845.
[21]
D'Onofrio M, Gallotti A, Mucelli RP (2010) Tissue quantification with acoustic radiation force impulse imaging: Measurement repeatability and normal values in the healthy liver. AJR Am J Roentgenol 195: 132–136.
[22]
Sporea I, Sirli RL, Deleanu A, Popescu A, Focsa M, et al. (2011) Acoustic radiation force impulse elastography as compared to transient elastography and liver biopsy in patients with chronic hepatopathies. Ultraschall Med 32: S46–52.
[23]
de Lédinghen V, Vergniol J (2010) Transient elastography for the diagnosis of liver fibrosis. Expert Rev Med Devices 7: 811–823.
[24]
Lindblad A, Glaumann H, Strandvik B (1999) Natural history of liver disease in cystic fibrosis. Hepatology 30: 1151–1158.
[25]
Chen AH, Innis SM, Davidson AG, James SJ (2005) Phosphatidylcholine and lysophosphatidylcholine excretion is increased in children with cystic fibrosis and is associated with plasma homocysteine, S-adenosylhomocysteine, and S-adenosylmethionine. Am J Clin Nutr 81: 686–691.
[26]
Nash KL, Allison ME, McKeon D, Lomas DJ, Haworth CS, et al. (2008) A single centre experience of liver disease in adults with cystic fibrosis 1995–2006. J Cyst Fibros 7: 252–257.
[27]
Gaia S, Carenzi S, Barilli AL, Bulgianesi E, Smedila A, et al. (2011) Reliability of transient elastography for the detection of fibrosis in non-alcoholic fatty liver disease and chronic viral hepatitis. J Hepatol 54: 64–71.
[28]
England K, Thorne C, Pembrey L, Tovo PA, Newell ML (2009) Age- and sex-related reference ranges of alanine aminotransferase levels in children: European paediatric HCV network. J Pediatr Gastroenterol Nutr 49: 71–77.
