Fontan-Associated Liver Disease: Pathophysiology, Staging, and Management

Abstract

Fontan-associated liver disease is the term used to encompass the disorders arising from abnormal hemodynamic alterations and systemic venous congestion after the Fontan procedure. The histological changes produced in the liver are similar but not equivalent to those seen in other forms of cardiac liver disease. While the natural history of this form of liver disease is poorly established, many Fontan patients ultimately develop portal hypertension-related complications such as ascites, esophageal varices, malnutrition, and encephalopathy. Fontan survivors also show an elevated risk of hepatocellular carcinoma. Adequate staging of the liver damage is essential to anticipate screening strategies and improve global management.

Keywords

Fontan-associated liver disease - Fontan surgery - cirrhosis - hepatocellular carcinoma

Publikationsverlauf

Artikel online veröffentlicht:
16. August 2021

• References

• 1 Téllez L, Rodríguez-Santiago E, Albillos A. Fontan-associated liver disease: a review. Ann Hepatol 2018; 17 (02) 192-204
• 2 Hebson CL, McCabe NM, Elder RW. et al. Hemodynamic phenotype of the failing Fontan in an adult population. Am J Cardiol 2013; 112 (12) 1943-1947
• 3 Alsaied T, Bokma JP, Engel ME. et al. Predicting long-term mortality after Fontan procedures: a risk score based on 6707 patients from 28 studies. Congenit Heart Dis 2017; 12 (04) 393-398
• 4 Rychik J, Veldtman G, Rand E. et al. The precarious state of the liver after a Fontan operation: summary of a multidisciplinary symposium. Pediatr Cardiol 2012; 33 (07) 1001-1012
• 5 Sessa A, Allaire M, Lebray P. et al. From congestive hepatopathy to hepatocellular carcinoma, how can we improve patient management?. JHEP Rep 2021; 3 (02) 100249
• 6 Downing TE, Allen KY, Glatz AC. et al. Long-term survival after the Fontan operation: twenty years of experience at a single center. J Thorac Cardiovasc Surg 2017; 154 (01) 243.e2-253.e2
• 7 Schilling C, Dalziel K, Nunn R. et al. The Fontan epidemic: population projections from the Australia and New Zealand Fontan Registry. Int J Cardiol 2016; 219: 14-19
• 8 Poh CL, d'Udekem Y. Life after surviving Fontan surgery: a meta-analysis of the incidence and predictors of late death. Heart Lung Circ 2018; 27 (05) 552-559
• 9 d'Udekem Y, Iyengar AJ, Galati JC. et al. Redefining expectations of long-term survival after the Fontan procedure: twenty-five years of follow-up from the entire population of Australia and New Zealand. Circulation 2014; 130 (11, Suppl 1): S32-S38
• 10 Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax 1971; 26 (03) 240-248
• 11 Gewillig M, Brown SC. The Fontan circulation after 45 years: update in physiology. Heart 2016; 102 (14) 1081-1086
• 12 Quinton E, Nightingale P, Hudsmith L. et al. Prevalence of atrial tachyarrhythmia in adults after Fontan operation. Heart 2015; 101 (20) 1672-1677
• 13 Seipelt RG, Franke A, Vazquez-Jimenez JF. et al. Thromboembolic complications after Fontan procedures: comparison of different therapeutic approaches. Ann Thorac Surg 2002; 74 (02) 556-562
• 14 Fernández-Iglesias A, Gracia-Sancho J. How to face chronic liver disease: the sinusoidal perspective. Front Med (Lausanne) 2017; 4: 7
• 15 Haggerty CM, Kanter KR, Restrepo M. et al. Simulating hemodynamics of the Fontan Y-graft based on patient-specific in vivo connections. J Thorac Cardiovasc Surg 2013; 145 (03) 663-670
• 16 Heinemann M, Breuer J, Steger V, Steil E, Sieverding L, Ziemer G. Incidence and impact of systemic venous collateral development after Glenn and Fontan procedures. Thorac Cardiovasc Surg 2001; 49 (03) 172-178
• 17 Faircloth JM, Roe O, Alsaied T, Palumbo JS, Vinks A, Veldtman GR. Intermediate term thrombotic risk in contemporary total cavo-pulmonary connection for single ventricle circulations. J Thromb Thrombolysis 2017; 44 (03) 275-280
• 18 Tomkiewicz-Pajak L, Hoffman P, Trojnarska O, Lipczyńska M, Podolec P, Undas A. Abnormalities in blood coagulation, fibrinolysis, and platelet activation in adult patients after the Fontan procedure. J Thorac Cardiovasc Surg 2014; 147 (04) 1284-1290
• 19 Simonetto DA, Yang HY, Yin M. et al. Chronic passive venous congestion drives hepatic fibrogenesis via sinusoidal thrombosis and mechanical forces. Hepatology 2015; 61 (02) 648-659
• 20 Sung PS, Yoon SK. Amiodarone hepatotoxicity. Hepatology 2012; 55 (01) 325-326
• 21 Wang A, Book WM, McConnell M, Lyle T, Rodby K, Mahle WT. Prevalence of hepatitis C infection in adult patients who underwent congenital heart surgery prior to screening in 1992. Am J Cardiol 2007; 100 (08) 1307-1309
• 22 Rodríguez de Santiago E, Téllez L, Garrido-Lestache Rodríguez-Monte E. et al. Fontan protein-losing enteropathy is associated with advanced liver disease and a proinflammatory intestinal and systemic state. Liver Int 2020; 40 (03) 638-645
• 23 Téllez L, Rodríguez de Santiago E, Albillos A. Fontan-associated liver disease. Rev Esp Cardiol (Engl Ed) 2018; 71 (03) 192-202
• 24 Baek JS, Bae EJ, Ko JS. et al. Late hepatic complications after Fontan operation; non-invasive markers of hepatic fibrosis and risk factors. Heart 2010; 96 (21) 1750-1755
• 25 Srinivasan A, Guzman AK, Rand EB. et al. Percutaneous liver biopsy in Fontan patients. Pediatr Radiol 2019; 49 (03) 342-350
• 26 Borquez AA, Silva-Sepulveda J, Lee JW. et al. Transjugular liver biopsy for Fontan associated liver disease surveillance: technique, outcomes and hemodynamic correlation. Int J Cardiol 2021; 328: 83-88
• 27 Kendall TJ, Stedman B, Hacking N. et al. Hepatic fibrosis and cirrhosis in the Fontan circulation: a detailed morphological study. J Clin Pathol 2008; 61 (04) 504-508
• 28 Goldberg DJ, Surrey LF, Glatz AC. et al. Hepatic fibrosis is universal following Fontan operation, and severity is associated with time from surgery: a liver biopsy and hemodynamic study. J Am Heart Assoc 2017; 6 (05) 6
• 29 Surrey LF, Russo P, Rychik J. et al. Prevalence and characterization of fibrosis in surveillance liver biopsies of patients with Fontan circulation. Hum Pathol 2016; 57: 106-115
• 30 Bosch DE, Koro K, Richards E. et al. Validation of a congestive hepatic fibrosis scoring system. Am J Surg Pathol 2019; 43 (06) 766-772
• 31 Vaikunth SS, Higgins JP, Concepcion W. et al. Does liver biopsy accurately measure fibrosis in Fontan-associated liver disease? A comparison of liver biopsy pre-combined heart and liver transplant and liver explant post-transplant. Clin Transplant 2020; 34 (12) e14120
• 32 Opotowsky AR, Baraona FR, Mc Causland FR. et al. Estimated glomerular filtration rate and urine biomarkers in patients with single-ventricle Fontan circulation. Heart 2017; 103 (06) 434-442
• 33 Fujishiro J, Sugiyama M, Ishimaru T. et al. Direct hyperbilirubinemia in infants with congenital heart disease. Pediatr Int (Roma) 2018; 60 (02) 179-182
• 34 Evans WN, Acherman RJ, Ciccolo ML. et al. MELD-XI scores correlate with post-Fontan hepatic biopsy fibrosis scores. Pediatr Cardiol 2016; 37 (07) 1274-1277
• 35 Bradley E, Hendrickson B, Daniels C. Fontan liver disease: review of an emerging epidemic and management options. Curr Treat Options Cardiovasc Med 2015; 17 (11) 51
• 36 Munsterman ID, Duijnhouwer AL, Kendall TJ. et al; Nijmegen Fontan Initiative. The clinical spectrum of Fontan-associated liver disease: results from a prospective multimodality screening cohort. Eur Heart J 2019; 40 (13) 1057-1068
• 37 McPherson S, Hardy T, Dufour JF. et al. Age as a confounding factor for the accurate non-invasive diagnosis of advanced NAFLD fibrosis. Am J Gastroenterol 2017; 112 (05) 740-751
• 38 Silva-Sepulveda JA, Fonseca Y, Vodkin I. et al. Evaluation of Fontan liver disease: correlation of transjugular liver biopsy with magnetic resonance and hemodynamics. Congenit Heart Dis 2019; 14: 600-608
• 39 Bae JM, Jeon TY, Kim JS. et al. Fontan-associated liver disease: spectrum of US findings. Eur J Radiol 2016; 85 (04) 850-856
• 40 Téllez L, Rodríguez de Santiago E, Mínguez B. et al; VALDIG an EASL consortium. Prevalence, features and predictive factors of liver nodules in Fontan surgery patients: the VALDIG Fonliver prospective cohort. J Hepatol 2020; 72 (04) 702-710
• 41 Kutty SS, Peng Q, Danford DA. et al; Liver Adult-Pediatric-Congenital-Heart-Disease Dysfunction Study (LADS) Group. Increased hepatic stiffness as consequence of high hepatic afterload in the Fontan circulation: a vascular Doppler and elastography study. Hepatology 2014; 59 (01) 251-260
• 42 Camposilvan S, Milanesi O, Stellin G, Pettenazzo A, Zancan L, D'Antiga L. Liver and cardiac function in the long term after Fontan operation. Ann Thorac Surg 2008; 86 (01) 177-182
• 43 Wallihan DB, Podberesky DJ. Hepatic pathology after Fontan palliation: spectrum of imaging findings. Pediatr Radiol 2013; 43 (03) 330-338
• 44 Bulut OP, Romero R, Mahle WT. et al. Magnetic resonance imaging identifies unsuspected liver abnormalities in patients after the Fontan procedure. J Pediatr 2013; 163 (01) 201-206
• 45 Chen B, Schreiberg RA, Human DG, Potts JE, Guttman OR. Assessment of liver stiffness in pediatric Fontan patients using transient elastography. Can J Gastroenterol Hepatol 2016; 2016: 7125193
• 46 Sugimoto M, Oka H, Kajihama A. et al. Non-invasive assessment of liver fibrosis by magnetic resonance elastography in patients with congenital heart disease undergoing the Fontan procedure and intracardiac repair. J Cardiol 2016; 68 (03) 202-208
• 47 Evans WN, Acherman RJ, Ciccolo ML. et al. A composite noninvasive index correlates with liver fibrosis scores in post-Fontan patients: preliminary findings. Congenit Heart Dis 2018; 13 (01) 38-45
• 48 Deorsola L, Aidala E, Cascarano MT, Valori A, Agnoletti G, Pace Napoleone C. Liver stiffness modifications shortly after total cavopulmonary connection. Interact Cardiovasc Thorac Surg 2016; 23 (04) 513-518
• 49 Agnoletti G, Ferraro G, Bordese R. et al. Fontan circulation causes early, severe liver damage. Should we offer patients a tailored strategy?. Int J Cardiol 2016; 209: 60-65
• 50 Alsaied T, Possner M, Lubert AM. et al. Relation of magnetic resonance elastography to Fontan failure and portal hypertension. Am J Cardiol 2019; 124 (09) 1454-1459
• 51 Egbe A, Miranda WR, Connolly HM, Khan AR, Al-Otaibi M, Venkatesh SK. et al. Temporal changes in liver stiffness after Fontan operation: Results of serial magnetic resonance elastography. 2018; 258: 299-304
• 52 Mori M, Hebson C, Shioda K. et al. Catheter-measured hemodynamics of adult fontan circulation: associations with adverse event and end-organ dysfunctions. Congenit Heart Dis 2016; 11 (06) 589-597
• 53 Egbe AC, Miranda WR, Veldtman GR, Graham RP, Kamath PS. Hepatic venous pressure gradient in Fontan physiology has limited diagnostic and prognostic significance. CJC Open 2020; 2 (05) 360-364
• 54 Aithal GP, Palaniyappan N, China L. et al. Guidelines on the management of ascites in cirrhosis. Gut 2021; 70 (01) 9-29
• 55 Wu FM, Jonas MM, Opotowsky AR. et al. Portal and centrilobular hepatic fibrosis in Fontan circulation and clinical outcomes. J Heart Lung Transplant 2015; 34 (07) 883-891
• 56 Bosch J, Abraldes JG, Albillos A. et al. Hipertensión portal: recomendaciones para su evaluación y tratamiento: Documento de consenso auspiciado por la AEEH y el CIBERehd. Gastroenterol Hepatol 2012; 35 (06) 421-450
• 57 Hilscher MB, Johnson JN, Cetta F. et al. Surveillance for liver complications after the Fontan procedure. Congenit Heart Dis 2017; 12 (02) 124-132
• 58 Pundi K, Pundi KN, Kamath PS. et al. Liver disease in patients after the Fontan operation. Am J Cardiol 2016; 117 (03) 456-460
• 59 Tellez L, Rodriguez de Santiago E, Garrido E. et al. High risk of esophageal varices in patients with Fontan surgery: the VALDIG Fonliver study. J Hepatol 2018; 68: S715 (Abstract)
• 60 Elder RW, McCabe NM, Hebson C. et al. Features of portal hypertension are associated with major adverse events in Fontan patients: the VAST study. Int J Cardiol 2013; 168 (04) 3764-3769
• 61 Machogu E, Balistrieri G, Hehir D, Quintero D. A case of tracheal varices in an adolescent patient with cyanotic heart disease. Ann Am Thorac Soc 2013; 10 (01) 26-30
• 62 de Franchis R. Baveno VI Faculty. Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol 2015; 63 (03) 743-752
• 63 Velpula M, Sheron N, Guha N, Salmon T, Hacking N, Veldtman GR. Direct measurement of porto-systemic gradient in a failing Fontan circulation. Congenit Heart Dis 2011; 6 (02) 175-178
• 64 Koteda Y, Suda K, Kishimoto S, Iemura M. Portal-systemic encephalopathy after Fontan-type operation in patient with polysplenia syndrome. Eur J Cardiothorac Surg 2009; 35: 1083-1085
• 65 Bryant T, Ahmad Z, Millward-Sadler H. et al. Arterialised hepatic nodules in the Fontan circulation: hepatico-cardiac interactions. Int J Cardiol 2011; 151 (03) 268-272
• 66 Poterucha JT, Johnson JN, Qureshi MY. et al. Magnetic resonance elastography: a novel technique for the detection of hepatic fibrosis and hepatocellular carcinoma after the Fontan operation. Mayo Clin Proc 2015; 90 (07) 882-894
• 67 Thrane KJ, Müller LSO, Suther KR, Thomassen KS, Holmström H, Thaulow E, Almaas R, Möller T, de Lange C. Spectrum of Fontan-associated liver disease assessed by MRI and US in young adolescents. Abdom Radiol (NY) 2021; 46 (07) 3205-3216
• 68 Kiesewetter CH, Sheron N, Vettukattill JJ. et al. Hepatic changes in the failing Fontan circulation. Heart 2007; 93 (05) 579-584
• 69 Horvat N, Rocha MS, Chagas AL. et al. Multimodality screening of hepatic nodules in patients with congenital heart disease after Fontan procedure: role of ultrasound, ARFI elastography, CT, and MRI. AJR Am J Roentgenol 2018; 211 (06) 1212-1220
• 70 Engelhardt EM, Trout AT, Sheridan RM, Veldtman GR, Dillman JR. Focal liver lesions following Fontan palliation of single ventricle physiology: a radiology-pathology case series. Congenit Heart Dis 2019; 14 (03) 380-388
• 71 Sempoux C, Balabaud C, Paradis V, Bioulac-Sage P. Hepatocellular nodules in vascular liver diseases. Virchows Arch 2018; 473 (01) 33-44
• 72 Cazals-Hatem D, Vilgrain V, Genin P. et al. Arterial and portal circulation and parenchymal changes in Budd-Chiari syndrome: a study in 17 explanted livers. Hepatology 2003; 37 (03) 510-519
• 73 Van Wettere M, Purcell Y, Bruno O. et al. Low specificity of washout to diagnose hepatocellular carcinoma in nodules showing arterial hyperenhancement in patients with Budd-Chiari syndrome. J Hepatol 2019; 70 (06) 1123-1132
• 74 Sagawa T, Kogiso T, Sugiyama H, Hashimoto E, Yamamoto M, Tokushige K. Characteristics of hepatocellular carcinoma arising from Fontan-associated liver disease. Hepatol Res 2020; 50 (07) 853-862
• 75 Nandwana SB, Olaiya B, Cox K, Sahu A, Mittal P. Abdominal imaging surveillance in adult patients after Fontan procedure: risk of chronic liver disease and hepatocellular carcinoma. Curr Probl Diagn Radiol 2018; 47 (01) 19-22
• 76 Rodríguez De Santiago E, Téllez L, Guerrero A, Albillos A. Hepatocellular carcinoma after Fontan surgery: a systematic review. Hepatol Res 2021; 51 (01) 116-134
• 77 Wells ML, Hough DM, Fidler JL, Kamath PS, Poterucha JT, Venkatesh SK. Benign nodules in post-Fontan livers can show imaging features considered diagnostic for hepatocellular carcinoma. Abdom Radiol (NY) 2017; 42 (11) 2623-2631
• 78 Possner M, Gordon-Walker T, Egbe AC. et al. Hepatocellular carcinoma and the Fontan circulation: clinical presentation and outcomes. Int J Cardiol 2021; 322: 142-148
• 79 European Association for the Study of the Liver. Electronic address: [e-mail], European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol 2018; 69: 182-236
• 80 Kwon S, Scovel L, Yeh M. et al. Surgical management of hepatocellular carcinoma after Fontan procedure. J Gastrointest Oncol 2015; 6 (03) E55-E60
• 81 Angelico R, Lisignoli V, Monti L. et al. Laparoscopic liver resection for hepatocellular carcinoma in Fontan-associated chronic liver disease. The first case report. Int J Surg Case Rep 2019; 59: 144-147
• 82 Weyker PD, Allen-John Webb C, Emond JC, Brentjens TE, Johnston TA. Anesthetic implications of extended right hepatectomy in a patient with fontan physiology. A A Case Rep 2014; 2 (08) 99-101
• 83 Rosenbaum J, Vrazas J, Lane GK, Hardikar W. Cardiac cirrhosis and hepatocellular carcinoma in a 13-year-old treated with doxorubicin microbead transarterial chemoembolization. J Paediatr Child Health 2012; 48 (03) E140-E143
• 84 Cho MK, Kwon JH, Gwak MS, Joh JW, Hwang J, Kim GS. Liver transplantation in an adult patient with hepatocellular carcinoma following liver cirrhosis as a complication of the Fontan procedure -A case report. Anesth Pain Med (Seoul) 2020; 15 (04) 466-471
• 85 Kovacikova L, Krasnanova V, Skrak P. et al. Immune abnormalities in patients with single ventricle circulation precede the Fontan procedure. World J Pediatr Congenit Heart Surg 2017; 8 (06) 672-682
• 86 Scheffers LE, Berg LEV, Ismailova G, Dulfer K, Takkenberg JJ, Helbing WA. Physical exercise training in patients with a Fontan circulation: a systematic review. Eur J Prev Cardiol 2020; (e-pub ahead of print) DOI: 10.1177/2047487320942869.
• 87 Weinreb SJ, Dodds KM, Burstein DS. et al. End-organ function and exercise performance in patients with Fontan circulation: what characterizes the high performers?. J Am Heart Assoc 2020; 9 (24) e016850
• 88 Warnes CA, Williams RG, Bashore TM. et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to develop guidelines for the management of adults with congenital heart disease). Circulation 2008; 118 (23) 2395-2451
• 89 Baumgartner H, Bonhoeffer P, De Groot NMS. et al; Task Force on the Management of Grown-up Congenital Heart Disease of the European Society of Cardiology (ESC), Association for European Paediatric Cardiology (AEPC), ESC Committee for Practice Guidelines (CPG). ESC Guidelines for the management of grown-up congenital heart disease (new version 2010). Eur Heart J 2010; 31 (23) 2915-2957
• 90 Daniels CJ, Bradley EA, Landberg MJ. et al. Fontan-associated liver disease: Proceedings from the American College of Cardiology Stakeholders Meeting, October 1 to 2, 2015, Washington DC. J Am Coll Cardiol 2017; 70 (25) 3173-3194
• 91 Rychik J, Atz AM, Celermajer DS. et al; American Heart Association Council on Cardiovascular Disease in the Young and Council on Cardiovascular and Stroke Nursing. Evaluation and management of the child and adult with Fontan circulation: A scientific statement from the American Heart Association. Circulation 2019; 140 (06) e234-e284
• 92 Zentner D, Celermajer DS, Gentles T. et al. Management of people with a Fontan circulation: a Cardiac Society of Australia and New Zealand position statement. Heart Lung Circ 2020; 29 (01) 5-39
• 93 Emamaullee J, Zaidi AN, Schiano T. et al. Fontan-associated liver disease: screening, management, and transplant considerations. Circulation 2020; 142 (06) 591-604
• 94 Simpson KE, Esmaeeli A, Khanna G. et al. Liver cirrhosis in Fontan patients does not affect 1-year post-heart transplant mortality or markers of liver function. J Heart Lung Transplant 2014; 33 (02) 170-177
• 95 Di Maria MV, Barrett C, Rafferty C. et al. Initiating a Fontan multidisciplinary clinic: decreasing care variability, improving surveillance, and subsequent treatment of Fontan survivors. Congenit Heart Dis 2019; 14 (04) 590-599
• 96 Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology 65: 310-335
• 97 Tabarsi N, Guan M, Simmonds J. et al. Meta-analysis of the effectiveness of heart transplantation in patients with a failing Fontan. Am J Cardiol 2017; 119 (08) 1269-1274
• 98 Simpson KE, Pruitt E, Kirklin JK. et al. Fontan patient survival after pediatric heart transplantation has improved in the current era. Ann Thorac Surg 2017; 103 (04) 1315-1320
• 99 Davies RR, Sorabella RA, Yang J, Mosca RS, Chen JM, Quaegebeur JM. Outcomes after transplantation for “failed” Fontan: a single-institution experience. J Thorac Cardiovasc Surg 2012; 143 (05) 1183.e4-1192.e4
• 100 Assenza GE, Graham DA, Landzberg MJ. et al. MELD-XI score and cardiac mortality or transplantation in patients after Fontan surgery. Heart 2013; 99 (07) 491-496
• 101 Lewis M, Ginns J, Schulze C. et al. Outcomes of adult patients with congenital heart disease after heart transplantation: impact of disease type, previous thoracic surgeries, and bystander organ dysfunction. J Card Fail 2016; 22 (07) 578-582
• 102 Berg CJ, Bauer BS, Hageman A, Aboulhosn JA, Reardon LC. Mortality risk stratification in Fontan patients who underwent heart transplantation. Am J Cardiol 2017; 119 (10) 1675-1679
• 103 D'Souza BA, Fuller S, Gleason LP. et al. Single-center outcomes of combined heart and liver transplantation in the failing Fontan. Clin Transplant 2017; 31 (03) 31
• 104 Zhao K, Wang R, Kamoun M. et al. Liver allograft provides protection against cardiac allograft rejection in combined heart and liver transplantation. Am J Transplant 2019; 19: 114
• 105 Ellis EL, Mann DA. Clinical evidence for the regression of liver fibrosis. J Hepatol 2012; 56 (05) 1171-1180
• 106 Crespo-Leiro MG, Robles O, Paniagua MJ. et al. Reversal of cardiac cirrhosis following orthotopic heart transplantation. Am J Transplant 2008; 8 (06) 1336-1339
• 107 Dichtl W, Vogel W, Dunst KM. et al. Cardiac hepatopathy before and after heart transplantation. Transpl Int 2005; 18 (06) 697-702
• 108 Bouchardy J, Meyer P, Yerly P. et al. Regression of advanced liver fibrosis after heart transplantation in a patient with prior Fontan surgery for complex congenital heart disease. Circ Heart Fail 2018; 11 (11) e003754