Hepatic Changes in the Fontan Circulation: Identification of Liver Dysfunction and an Attempt to Streamline Follow-up Screening
We tried to identify structural and functional liver aberrances in a palliated Fontan population and sought to determine useful screening modalities, in order to propose a screening protocol to detect patients at risk. Twenty nine patients, median age 23.7 years (interquartile range (IQR) 20.5–27.2) and median Fontan interval 19.7 years (IQR 4.5–21.4), were prospectively studied with echocardiography, blood analysis (including serum fibrosis scores Forns, APRI and FIB4), liver imaging (ultrasound (US), Doppler), and shear wave elastography to determine liver stiffness (LS). Laboratory tests predominantly showed abnormal values for gamma-glutamyltransferase. Forns index indicated moderate fibrosis in 29% of patients and correlated with Fontan interval (p = 0.034). US liver morphology was deviant in 46% of patients, with surface nodularity in 21% and nodular hyperplasia in 29%. Doppler assessment of flow velocities was within normal ranges for most patients. LS (mean 10.4 ± 3.7 kPa) was elevated in 96% of our population and higher LS values were significantly related to longer Fontan interval (p = 0.018). Adolescent and adult Fontan patients show moderate signs of liver dysfunction. Usefulness of serum parameters and fibrosis scores in post-Fontan screening remains ambiguous. The high percentage of morphologic liver changes in palliated patients supports the use of US in periodic follow-up. LS likely overestimates fibrosis due to liver congestion, arguing for the need of validation through sequential measurements. Screening should minimally encompass US assessment in combination with selective liver fibrosis scores. The role of LS measurement in Fontan follow-up and liver screening needs to be further elucidated.
KeywordsUniventricular heart Fontan circulation Cardiac hepatopathy Serum markers Elastography Screening
AST-to-platelet ratio index
Chronic right heart failure
Central venous pressure
Focal nodular hyperplasia
Inferior caval vein
Magnetic resonance imaging
New York Heart Association
Superior mesenteric artery
Shear wave elastography
Total cavopulmonary connection
Compliance with Ethical Standards
Conflict of interest
All authors declare that he/she has no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 5.Kiesewetter CH, Sheron N, Vettukattill JJ, Hacking N, Stedman B, Millward-Sadler H, Haw M, Cope R, Salmon AP, Sivaprakasam MC, Kendall T, Keeton BR, Iredale JP, Veldtman GR (2007) Hepatic changes in the failing Fontan circulation. Heart 93:579–584. https://doi.org/10.1136/hrt.2006.094516 CrossRefPubMedGoogle Scholar
- 7.Ghaferi AA, Hutchins GM (2005) Progression of liver pathology in patients undergoing the Fontan procedure: chronic passive congestion, cardiac cirrhosis, hepatic adenoma, and hepatocellular carcinoma. J Thorac Cardiovasc Surg 129:1348–1352. https://doi.org/10.1016/j.jtcvs.2004.10.005 CrossRefPubMedGoogle Scholar
- 8.Josephus Jitta D, Wagenaar LJ, Mulder BJM, Guichelaar M, Bouman D, Van Melle JP (2016) Three cases of hepatocellular carcinoma in Fontan patients: review of the literature and suggestions for hepatic screening. Int J Cardiol 206:21–26. https://doi.org/10.1016/j.ijcard.2015.12.033 CrossRefPubMedGoogle Scholar
- 11.Elder RW, McCabe NM, Hebson C, Veledar E, Romero R, Ford RM, Mahle WT, Kogon BE, Sahu A, Jokhadar M, McConnell ME, Book WM (2013) Features of portal hypertension are associated with major adverse events in Fontan patients: the VAST study. Int J Cardiol 168:3764–3769. https://doi.org/10.1016/j.ijcard.2013.06.008 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Assenza GE, Graham D, Landzberg MJ, Valente AM, Singh MN, Bashir A, Fernandes S, Mortele KJ, Ukomadu C, Volpe M, Wu F (2013) MELD-XI score and cardiac mortality or transplantation in patients after Fontan surgery. Heart 99:491–496. https://doi.org/10.1136/heartjnl-2012-303347 CrossRefPubMedGoogle Scholar
- 16.Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, Sulkowski MS, Torriani FJ, Dieterich DT, Thomas DL, Messinger D, Nelson M (2006) Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 43:1317–1325. https://doi.org/10.1002/hep.21178 CrossRefPubMedGoogle Scholar
- 29.Poelzl G, Eberl C, Achrainer H, Doerler J, Pachinger O, Frick M, Ulmer H (2009) Prevalence and prognostic significance of elevated gamma-glutamyltransferase in chronic heart failure. Circ Heart Fail 2:294–302. https://doi.org/10.1161/CIRCHEARTFAILURE.108.826735 CrossRefPubMedGoogle Scholar
- 32.Grigorescu M (2006) Noninvasive biochemical markers of liver fibrosis. J Gastrointest Liver Dis 15:149–159Google Scholar
- 37.Hsia TY, Khambadkone S, Redington a N, Migliavacca F, Deanfield JE, de Leval MR (2000) Effects of respiration and gravity on infradiaphragmatic venous flow in normal and Fontan patients. Circulation 102:III148–III153. https://doi.org/10.1161/01.CIR.102.suppl_3.III-148 CrossRefPubMedGoogle Scholar
- 38.Hebson CL, McCabe NM, Elder RW, Mahle WT, McConnell M, Kogon BE, Veledar E, Jokhadar M, Vincent RN, Sahu A, Book WM (2013) Hemodynamic phenotype of the failing Fontan in an adult population. Am J Cardiol 112:1943–1947. https://doi.org/10.1016/j.amjcard.2013.08.023 CrossRefPubMedPubMedCentralGoogle Scholar
- 43.Poynard T, Lenaour G, Vaillant JC, Capron F, Munteanu M, Eyraud D, Ngo Y, M’Kada H, Ratziu V, Hannoun L, Charlotte F (2012) Liver biopsy analysis has a low level of performance for diagnosis of intermediate stages of fibrosis. Clin Gastroenterol Hepatol. https://doi.org/10.1016/j.cgh.2012.01.023 CrossRefPubMedGoogle Scholar