The study by Chappell et al. evaluates the outcomes of combined heart-liver transplantation in patients with Fontan circulation treated at pediatric hospitals across the United States. This was a retrospective multicenter study based on a linked database from the Pediatric Health Information System and the United Network for Organ Sharing. The authors identified 34 patients who underwent combined heart-liver transplantation between 2010 and 2024 at 9 pediatric hospitals and compared their outcomes with those of a matched cohort of Fontan patients undergoing isolated heart transplantation.

Although the sample size was limited, the study is of particular interest because it reflects nationwide experience in a rare and highly complex patient population. It also demonstrates a clear temporal trend: 82% of combined heart-liver transplants were performed from 2019 onward. This increase probably reflects the progressive aging of the Fontan population, growing awareness of Fontan-associated liver disease, and the increasing establishment of combined transplantation as a therapeutic option at experienced centers.

The cohort included pediatric patients and young adults, with a median age of 19 years. Almost half were aged 18 years or younger at the time of transplantation. Clinically, this was a high-risk population: 59% were hospitalized before transplantation, 24% were receiving inotropic support, 18% had renal dysfunction, and some patients required dialysis, mechanical ventilation, ECMO, or ventricular assist device support. Cirrhosis was the most common hepatic indication, accounting for 71% of transplant indications, whereas 12% had primary hepatic malignancy. Ascites was present in 41%, and one-third had a MELD/PELD score of 10 or lower, underscoring the limitations of these scoring systems in accurately reflecting the severity of liver disease in Fontan physiology.

The reported outcomes were favorable, although they should be interpreted cautiously. Overall 1-year survival was 85%, with better outcomes among adults than pediatric patients. Overall mortality was 15%; however, all deaths occurred before hospital discharge and within the first 6 months. No patient who survived to discharge died during subsequent follow-up, which averaged more than 4 years. This concentration of mortality within the perioperative period is one of the most relevant findings of the study: the major risk associated with combined heart-liver transplantation appears to occur early, whereas patients who survive this initial phase seem to experience a more favorable subsequent course.

Comparison with isolated heart transplantation provides another important finding. Three-year survival was similar between groups, at 85% after combined heart-liver transplantation and 84% after isolated heart transplantation. Among patients surviving beyond 6 months, 3-year survival was 100% in the combined transplantation group compared with 92% in the isolated heart transplantation group, although the difference was not statistically significant. In addition, no treated cardiac rejection was observed in the heart-liver transplantation group, compared with 19% in the isolated heart transplantation group. Although this observation is limited by the retrospective design and small sample size, it is consistent with the potential immunomodulatory effect of the liver graft described in other multiorgan transplantation settings.

COMMENTARY:

The study by Chappell et al. supports combined heart-liver transplantation as a feasible strategy with encouraging outcomes in selected Fontan patients. Its main advantage is clear: it allows simultaneous treatment of both Fontan circulatory failure and advanced liver disease that may not resolve after isolated heart transplantation. In patients with established cirrhosis, clinically significant portal hypertension, recurrent ascites, varices, substantial splenomegaly, or hepatic lesions suspicious for malignancy, heart transplantation alone may leave a major component of morbidity and mortality untreated.

Another potential advantage is immunologic protection. The absence of treated cardiac rejection in the combined transplant cohort does not allow definitive conclusions, but it is noteworthy and supports the hypothesis that the liver may exert a protective effect on the cardiac graft. This possibility is particularly relevant in Fontan patients, who often have complex anatomy, multiple previous surgical procedures, and potential immunologic sensitization.

However, combined heart-liver transplantation should not be regarded as a universal solution for every Fontan patient with hepatic abnormalities. Fontan-associated liver disease is highly prevalent and, to some extent, almost intrinsic to long-standing Fontan circulation. The challenge is therefore not to identify any degree of fibrosis, but rather to distinguish patients with advanced, irreversible, or clinically significant liver disease severe enough to justify transplantation of two organs. This distinction carries important medical, surgical, and ethical implications in the context of limited donor organ availability.

The disadvantages are substantial. Combined transplantation is technically demanding, carries considerable perioperative risk, and requires extensive healthcare resources. In the reported series, hospital length of stay was prolonged, 18% of patients required dialysis after transplantation, 15% required postoperative ECMO, 12% experienced stroke, and initial costs were clearly higher than those associated with isolated heart transplantation. In addition, in-hospital mortality was 15% and reached 25% among pediatric patients. These findings caution against an overly optimistic interpretation: combined transplantation may provide excellent mid-term outcomes, but only in patients who survive a high-risk early postoperative phase.

The key issue is timing of referral and transplantation. The study suggests that some patients may reach transplantation too late, once advanced clinical decompensation has already developed. Almost 60% of the cohort was hospitalized before the procedure, and a substantial proportion had renal dysfunction, required inotropes, or needed mechanical circulatory support. In failing Fontan circulation, waiting until cachexia, renal failure, refractory ascites, mechanical ventilation, or nutritional deterioration develops is likely to reduce the likelihood of a favorable outcome.

Conversely, early combined transplantation for any manifestation of Fontan-associated liver disease also appears difficult to justify. The optimal timing lies within a narrow therapeutic window: sufficiently late for the surgical risk and use of two donor organs to be warranted, but sufficiently early to avoid progression to multiorgan dysfunction that makes transplantation excessively hazardous. Identifying this window requires longitudinal follow-up within structured multidisciplinary programs.

Assessment should therefore be multidisciplinary and should not rely on a single marker. Transaminase levels may remain relatively unremarkable, MELD/PELD may underestimate the severity of Fontan-associated liver disease, and elastography may be affected by hepatic congestion. The decision should consequently integrate cardiac, hemodynamic, hepatic, renal, nutritional, and functional parameters. Evaluation should include ventricular function, atrioventricular valve regurgitation, Fontan circuit pressures, pulmonary vascular resistance, functional capacity, arrhythmias, protein-losing enteropathy, renal function, ascites, varices, splenomegaly, hepatic nodules, and, in selected cases, liver biopsy.

Before transplantation is considered, potentially correctable abnormalities within the Fontan circuit must be excluded. Pulmonary artery branch lesions, conduit obstruction, significant collateral vessels, treatable arrhythmias, or valvular regurgitation may alter the clinical course. In selected patients, ventricular assist device support may also serve as a bridge to transplantation by improving hemodynamic, renal, and nutritional status.

In conclusion, the study by Chappell et al. provides grounds for cautious optimism. At experienced pediatric centers, combined heart-liver transplantation can achieve survival comparable to isolated heart transplantation, with excellent subsequent outcomes among patients who survive the perioperative period. Nevertheless, it remains a highly complex strategy with indications that are not yet fully established. In failing Fontan circulation, the fundamental question is not only whether to transplant the heart alone or both the heart and liver, but when to recognize that the disease has progressed beyond isolated cardiac failure and evolved into potentially irreversible multiorgan dysfunction.

REFERENCE:

Chappell G, Mehdizadeh-Shrifi A, Turner D, Bondoc A, Evans S, Miethke AG, et al. Outcomes of Fontan patients undergoing combined heart-liver transplantation in pediatric hospitals across the United States. J Thorac Cardiovasc Surg. 2026 Jan;171(1):288-297.e2. doi: 10.1016/j.jtcvs.2025.08.011. Epub 2025 Aug 14. PMID: 40818789; PMCID: PMC12969833.