Advertisement

Pediatric Cardiology

, Volume 39, Issue 8, pp 1604–1613 | Cite as

Hepatic Changes in the Fontan Circulation: Identification of Liver Dysfunction and an Attempt to Streamline Follow-up Screening

  • T. Ackerman
  • A. Geerts
  • H. Van Vlierberghe
  • J. De Backer
  • K. François
Original Article

Abstract

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.

Keywords

Univentricular heart Fontan circulation Cardiac hepatopathy Serum markers Elastography Screening 

Abbreviations

AFP

Alfa-fetoprotein

ALT

Alanine aminotransferase

APRI

AST-to-platelet ratio index

AST

Aspartate aminotransferase

CRHF

Chronic right heart failure

CVP

Central venous pressure

FIB-4

Fibrosis 4

FNH

Focal nodular hyperplasia

FU

Follow-up

GGT

Gamma-glutamyl transferase

HA

Hepatic artery

HCC

Hepatocellular carcinoma

HV

Hepatic vein

ICV

Inferior caval vein

IQR

Interquartile range

LS

Liver stiffness

MRI

Magnetic resonance imaging

NYHA

New York Heart Association

PI

Pulsatility index

PV

Portal vein

RU

Resistance index

SMA

Superior mesenteric artery

SWE

Shear wave elastography

TCPC

Total cavopulmonary connection

US

Ultrasound

UVH

Univentricular heart

Notes

Compliance with Ethical Standards

Conflict of interest

All authors declare that he/she has no conflict of interest.

Ethical Approval

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

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Rychik J (2016) The relentless effects of the Fontan paradox. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 19:37–43.  https://doi.org/10.1053/j.pcsu.2015.11.006 CrossRefPubMedGoogle Scholar
  2. 2.
    Hsia TY, Khambadkone S, Deanfield JE, Taylor JFN, Migliavacca F, De Leval MR (2001) Subdiaphragmatic venous hemodynamics in the Fontan circulation. J Thorac Cardiovasc Surg 121:436–447.  https://doi.org/10.1067/mtc.2001.112527 CrossRefPubMedGoogle Scholar
  3. 3.
    Nakamura Y, Yagihara T, Kagisaki K, Hagino I, Kobayashi J (2011) Ventricular performance in long-term survivors after Fontan operation. Ann Thorac Surg 91:172–180.  https://doi.org/10.1016/j.athoracsur.2010.07.055 CrossRefPubMedGoogle Scholar
  4. 4.
    Asrani SK, Asrani NS, Freese DK, Phillips SD, Warnes CA, Heimbach J, Kamath PS (2012) Congenital heart disease and the liver. Hepatology 56:1160–1169.  https://doi.org/10.1002/hep.25692 CrossRefPubMedGoogle Scholar
  5. 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
  6. 6.
    Camposilvan S, Milanesi O, Stellin G, Pettenazzo A, Zancan L, D’Antiga L (2008) Liver and cardiac function in the long term after Fontan operation. Ann Thorac Surg 86:177–182.  https://doi.org/10.1016/j.athoracsur.2008.03.077 CrossRefPubMedGoogle Scholar
  7. 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. 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
  9. 9.
    Rajoriya N, Clift P, Thorne S, Hirschfield GM, Ferguson JW (2014) A liver mass post-fontan operation. Q J Med 107:571–572.  https://doi.org/10.1093/qjmed/hcu020 CrossRefGoogle Scholar
  10. 10.
    Wallihan DB, Podberesky DJ (2013) Hepatic pathology after Fontan palliation: spectrum of imaging findings. Pediatr Radiol 43:330–338.  https://doi.org/10.1007/s00247-012-2531-y CrossRefPubMedGoogle Scholar
  11. 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. 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
  13. 13.
    Ofei SY, Gariepy C, Hanje J, Sisk T, Daniels CJ, Zaidi AN (2015) Liver fibrosis in adults with Fontan palliation: do common screening studies predict disease severity? Int J Cardiol 181:174–175.  https://doi.org/10.1016/j.ijcard.2014.12.031 CrossRefPubMedGoogle Scholar
  14. 14.
    Forns X, Ampurdanes S, Llovet JM, Aponte J, Quinto L, Martinez-Bauer E, Bruguera M, Sanchez-Tapias JM, Rodes J (2002) Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology 36:986–992CrossRefGoogle Scholar
  15. 15.
    Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, Lok AS (2003) A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 38:518–526.  https://doi.org/10.1053/jhep.2003.50346 CrossRefPubMedGoogle Scholar
  16. 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
  17. 17.
    McNaughton DA, Abu-Yousef MM (2011) Doppler US of the liver made simple. Radiographics 31:161–188.  https://doi.org/10.1148/rg.311105093 CrossRefPubMedGoogle Scholar
  18. 18.
    Ferraioli G, Parekh P, Levitov AB, Filice C (2014) Shear wave elastography for evaluation of liver fibrosis. J Ultrasound Med 33:197–203.  https://doi.org/10.7863/ultra.33.2.197 CrossRefPubMedGoogle Scholar
  19. 19.
    Kaulitz R, Haber P, Sturm E, Schäfer J, Hofbeck M (2014) Serial evaluation of hepatic function profile after Fontan operation. Herz 39:98–104.  https://doi.org/10.1007/s00059-013-3811-5 CrossRefPubMedGoogle Scholar
  20. 20.
    Lindsay I, Johnson J, Everitt MD, Hoffman J, Yetman AT (2015) Impact of liver disease after the fontan operation. Am J Cardiol 115:249–252.  https://doi.org/10.1016/j.amjcard.2014.10.032 CrossRefPubMedGoogle Scholar
  21. 21.
    Cromme-Dijkhuis AH, Hess J, Hählen K, Henkens CM, Bink-Boelkens MT, Eygelaar AA, Bos E (1993) Specific sequelae after Fontan operation at mid- and long-term follow-up. Arrhythmia, liver dysfunction, and coagulation disorders. J Thorac Cardiovasc Surg 106:1126–1132PubMedGoogle Scholar
  22. 22.
    Tomita H, Yamada O, Ohuchi H, Ono Y, Arakaki Y, Yagihara T, Echigo S (2001) Coagulation profile, hepatic function, and hemodynamics following Fontan-type operations. Cardiol Young 11:62–66CrossRefGoogle Scholar
  23. 23.
    van Nieuwenhuizen RC, Peters M, Lubbers LJ, Trip MD, Tijssen JG, Mulder BJ (1999) Abnormalities in liver function and coagulation profile following the Fontan procedure. Heart 82:40–46.  https://doi.org/10.1136/hrt.82.1.40 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Chaloupecky V, Svobodova I, Hadacova I, Tomek V, Hucin B, Tlaskal T, Janousek J, Reich O, Skovranek J (2005) Coagulation profile and liver function in 102 patients after total cavopulmonary connection at mid term follow up. Heart 91:73–79CrossRefGoogle Scholar
  25. 25.
    Schwartz MC, Glatz AC, Daniels K, Goldberg DJ, Rand E, Epelman MS, Cohen MS (2015) Hepatic abnormalities are present before and early after the fontan operation. Ann Thorac Surg 100:2298–2304.  https://doi.org/10.1016/j.athoracsur.2015.06.071 CrossRefPubMedGoogle Scholar
  26. 26.
    Lau GT, Tan HC, Kritharides L (2002) Type of liver dysfunction in heart failure and its relation to the severity of tricuspid regurgitation. Am J Cardiol 90:1405–1409CrossRefGoogle Scholar
  27. 27.
    Vasconcelos LA, de Almeida EA, Bachur LF (2007) Clinical evaluation and hepatic laboratory assessment in individuals with congestive heart failure. Arq Bras Cardiol 88:590–595CrossRefGoogle Scholar
  28. 28.
    Cogger VC, Fraser R, Le Couteur DG (2003) Liver dysfunction and heart failure. Am J Cardiol 91:1399.  https://doi.org/10.1016/S0002-9149(03)00370-9 CrossRefPubMedGoogle Scholar
  29. 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
  30. 30.
    Koehne de Gonzalez AK, Lefkowitch JH (2017) Heart disease and the liver. Gastroenterol Clin N Am 46:421–435.  https://doi.org/10.1016/j.gtc.2017.01.012 CrossRefGoogle Scholar
  31. 31.
    Afdhal NH, Nunes D (2004) Evaluation of liver fibrosis: a concise review. Am J Gastroenterol 99:1160–1174.  https://doi.org/10.1111/j.1572-0241.2004.30110.x CrossRefGoogle Scholar
  32. 32.
    Grigorescu M (2006) Noninvasive biochemical markers of liver fibrosis. J Gastrointest Liver Dis 15:149–159Google Scholar
  33. 33.
    Schwartz MC, Sullivan LM, Glatz AC, Rand E, Russo P, Goldberg DJ, Rome JJ, Cohen MS (2013) Portal and sinusoidal fibrosis are common on liver biopsy after fontan surgery. Pediatr Cardiol 34:135–142.  https://doi.org/10.1007/s00246-012-0402-9 CrossRefPubMedGoogle Scholar
  34. 34.
    Furukawa T, Akimoto K, Ohtsuki M, Sato K, Suzuki M, Takahashi K, Kishiro M, Shimizu T, Kawasaki S (2011) Non-invasive assessment of liver fibrosis in patients after the Fontan operation. Pediatr Int 53:980–984.  https://doi.org/10.1111/j.1442-200X.2011.03497.x CrossRefPubMedGoogle Scholar
  35. 35.
    Baek JS, Bae EJ, Ko JS, Kim GB, Kwon BS, Lee SY, Noh C, Park E-A, Lee W (2010) Late hepatic complications after Fontan operation; non-invasive markers of hepatic fibrosis and risk factors. Heart 96:1750–1755.  https://doi.org/10.1136/hrt.2010.201772 CrossRefPubMedGoogle Scholar
  36. 36.
    Shimizu M, Miyamoto K, Nishihara Y, Izumi G, Sakai S, Inai K, Nishikawa T, Nakanishi T (2015) Risk factors and serological markers of liver cirrhosis after Fontan procedure. Heart Vessels.  https://doi.org/10.1007/s00380-015-0743-4 CrossRefPubMedGoogle Scholar
  37. 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. 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
  39. 39.
    Schwartz MC, Sullivan L, Cohen MS, Russo P, John AS, Guo R, Guttenberg M, Rand EB (2012) Hepatic pathology may develop before the Fontan operation in children with functional single ventricle: an autopsy study. J Thorac Cardiovasc Surg 143:904–909CrossRefGoogle Scholar
  40. 40.
    DiPaola FW, Schumacher KR, Goldberg CS, Friedland-Little J, Parameswaran A, Dillman JR (2016) Effect of Fontan operation on liver stiffness in children with single ventricle physiology. Eur Radiol.  https://doi.org/10.1007/s00330-016-4614-x CrossRefPubMedGoogle Scholar
  41. 41.
    Deorsola L, Aidala E, Cascarano MT, Valori A, Agnoletti G, Napoleone CP (2016) Liver stiffness modifications shortly after total cavopulmonary connection. Interact Cardiovasc Thorac Surg.  https://doi.org/10.1093/icvts/ivw186 CrossRefPubMedGoogle Scholar
  42. 42.
    Šimonovský V (1999) The diagnosis of cirrhosis by high resolution ultrasound of the liver surface. Br J Radiol 72:29–34.  https://doi.org/10.1259/bjr.72.853.10341686 CrossRefPubMedGoogle Scholar
  43. 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

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Cardiac SurgeryUniversity Hospital GhentGhentBelgium
  2. 2.Department of HepatologyUniversity Hospital GhentGhentBelgium
  3. 3.Department of CardiologyUniversity Hospital GhentGhentBelgium

Personalised recommendations