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Fontan-Associated Liver Disease: Reversible with Cardiac Transplantation, or "Past the Point of No Return"?

Kathleen E. Simpson, MD
Washington University Saint Louis
Saint Louis, MO, USA

Melanie D. Everitt, MD
Primary Children's Medical Center
Salt Lake City, Utah, USA

Since the success of palliative procedures for complex single ventricle cardiac defects, there has been a shift in the need for heart transplantation as primary therapy for infants with single ventricles to the need for heart transplantation in adolescence or young adulthood for late heart failure and complications arising from the passive venous-to-pulmonary artery circulation of the Fontan procedure. While protein-losing enteropathy, systolic heart failure, and plastic bronchitis are well described complications of the Fontan procedure, there has been growing awareness of Fontan-associated liver disease. Many questions arise in terms of the impact of Fontan-associated liver disease on heart transplant mortality and the reversibility of the disease process after heart transplant.

The good news is that reports examining the current era of heart transplantation indicate improving outcomes for all recipients, including those with complex congenital heart disease [1]. Moreover, a history of Fontan procedure may not be associated with the same mortality risk in the current era of heart transplantation as in earlier eras [2]. Complete assessment of the transplant candidate with complex congenital heart disease in terms of mortality risk from the cardiac disease as well as from associated morbidities contributes to improved outcomes and has become a hot topic for pediatric and congenital heart disease specialists.

And so, along comes the patient with Fontan-associated liver disease. A 19-year-old with longstanding protein-losing enteropathy, ascites, muscle-wasting, lower extremity edema to above the knees, cutaneous angiomas, and hypoxemia secondary to pulmonary arterio-venous malformations presents for heart transplant evaluation. Other than the low albumin, laboratory studies do not show synthetic liver dysfunction. As part of the evaluation, you obtain a liver scan. You ask your hepatologist to perform a liver biopsy which is interpreted as "marked fibrosis". What does this mean for your patient's operative risk and potential for recovery? Should you recommend heart transplant, liver-heart transplant, or consider the patient too high risk for transplant?

The presence of liver fibrosis has been previously described in a substantial portion of Fontan patients at follow-up. The development of liver disease is thought to be multi-factorial, in part due to the after effects of the Fontan procedure as well as years of passive venous congestion and volume overload [3]. Liver biopsy remains the gold standard for assessment of liver disease but, due to the risks of bleeding complications, noninvasive imaging is more feasible for serial monitoring. Unfortunately, the optimal mode of imaging is not clear in this patient population as the disease is different from other cirrhotic processes. Liver ultrasound with Doppler to assess for hepatofugal flow, computed tomography (CT), or magnetic resonance imaging (MRI) have been used to various degrees depending upon the institution. In general, there is an extended period of time after the Fontan in childhood when liver fibrosis develops and progresses without alterations in synthetic liver function [4,5]. Research in mainly rodent models has also suggested liver fibrosis may even be reversible to a point, but this has not been well studied in in humans and the threshold of liver damage leading to overt liver dysfunction is unknown [6].

There is no consensus on whether the presence of severe liver disease requires combined heart-liver transplantation in Fontan patients. Hollander et al reported successful combined heart-liver transplantation in 3 single ventricle patients with severe liver fibrosis by imaging, including patients with relatively intact synthetic function, although the authors note the decision for combined transplantation was based on presumed increased risk with heart only transplantation [7]. Unfortunately, there are limited reports of post-transplant outcomes in Fontan patients with evidence of severe liver fibrosis who underwent heart transplant alone. In 2005 at St. Louis Children's Hospital, liver imaging became a routine part of pre-transplant evaluation in Fontan patients. Of those with liver cirrhosis who undergo heart transplant, 1 year mortality has been similar to previously published outcomes in Fontan patients, and we have seen no significant difference between those with and without liver cirrhosis [8]. In the majority of patients with evidence of liver cirrhosis on CT scan, synthetic liver function appeared normal at transplant evaluation and no patients had liver dysfunction post-transplant.

Intuitively, in single ventricle patients with liver fibrosis without detectable synthetic liver dysfunction, correction of the abnormal physiology with heart transplantation may halt progression of liver dysfunction and even possibly allow for reversal of liver changes. In fact, there is at least one case report to date of complete regression of cardiac cirrhosis after heart transplantation in a patient with a 12-year history of heart failure from dilated cardiomyopathy [9]. Therefore, liver fibrosis and cirrhosis may not be a contraindication to heart transplant alone in those patients who have normal liver synthetic function despite abnormal liver imaging or even biopsy findings. Further studies are required to evaluate liver changes after transplantation in single ventricle patients to understand the degree of reversibility of fibrosis and long-term post-transplant outcomes.

The current practice at our centers is to proceed with heart transplant alone in most cases. Liver transplant is reserved for those patients who meet standard criteria for liver transplant. Namely, in other forms of liver disease, the presence of cirrhosis alone does not warrant organ transplantation so the mere presence of cirrhosis by biopsy or noninvasive imaging in the Fontan patient has not obligated combined heart-liver transplant. It is the complications of portal hypertension and synthetic dysfunction (i.e. variceal hemorrhage, encephalopathy, hepato-renal syndrome) or hepatocellular carcinomas that drive liver transplant consideration. In other words, if the function of the liver is such that the patient is anticipated to survive heart transplant alone, then heart transplant alone is performed. Serial follow-up of the liver disease is imperative, however, as the development of hepatocellular carcinoma after heart transplant in the Fontan patient has been observed [10].

Disclosure Statement: The authors have no conflicts of interest to disclose.


  1. Chen JM, Davies RR, Mital SR, et al. Trends and outcomes in transplantation for complex congenital heart disease: 1984-2004. Ann Thorac Surg 2004;78(4):1352-61.
  2. Bhama JK, Shulman J, Bermudez CA, et al. Heart transplantation for adults with congenital heart disease: results in the modern era. J Heart Lung Transplant 2013:32(5):499-504.
  3. Asrani SK, Asrani NS, Freese DK, et al. Congenital heart disease and the liver. Hepatology. 2012;56:1160-1169.
  4. Furukawa T, Akimoto K, Ohtsuki M, et al. Non-invasive assessment of liver fibrosis in patients after the fontan operation. Pediatrics international: official journal of the Japan Pediatric Society. 2011;53:980-984.
  5. 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;96:1750-55.
  6. Ellis EL, Mann DA. Clinical evidence for the regression of liver fibrosis. Journal of hepatology. 2012;56:1171-1180.
  7. Hollander SA, Reinhartz O, Maeda K, et al. Intermediate-term outcomes after combined heart-liver transplantation in children with a univentricular heart. J Heart Lung Transplant 2013;32:368-370.
  8. Simpson KE, Esmaeeli A, Khanna G, et al. J Heart Lung Transplant 2013;32(4):S36
  9. Crespo-Leiro MG, Robles O, Paniagua MJ, et al. Reversal of cardiac cirrhosis following orthotopic heart transplantation. American J Transplant 2008;8:1336-39.
  10. Elder RW, Parekh S, Book WM. More on hepatocellular carcinoma after the Fontan procedure. N Engl J Med 2013;369:490.

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