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

Luis Téllez; Enrique Rodríguez de Santiago; Agustín Albillos

doi:10.1055/s-0041-1732355

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2021; 41(04): 538-550
DOI: 10.1055/s-0041-1732355

Review Article

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

Luis Téllez

¹Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Centro de Investigación Biomédica en Red (CIBEREHD), Universidad de Alcalá, Madrid, Spain

,

Enrique Rodríguez de Santiago

¹Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Centro de Investigación Biomédica en Red (CIBEREHD), Universidad de Alcalá, Madrid, Spain

,

Agustín Albillos

¹Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Centro de Investigación Biomédica en Red (CIBEREHD), Universidad de Alcalá, Madrid, Spain

› Author Affiliations

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

Full Text

References

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: easloffice@easloffice.eu, 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)
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