EXPLANATION

Combined heart-liver transplants (CHLT) remain uncommon, particularly in pediatric patients. The first successful CHLT was performed in 1984 in a 6-year-old girl with homozygous familial hypercholesterolemia resulting in ischemic cardiomyopathy, who survived for six years after transplantation. Between 1988 and 2023, only 30 pediatric CHLT were performed in the United States. Most recipients were adolescents, although the youngest reported recipient was a 2-year-old child with Alagille syndrome. Despite this rarity, the number of CHLTs is increasing, largely due to improved survival among patient with Fontan circulation and the growing burden of Fontan-associated liver disease (FALD). It is estimated that more than 70,000 individuals worldwide are living with Fontan physiology, and this population is expected to double over the next decade. Congenital heart disease, particularly failing Fontan circulation, is now the leading indication for CHLT in children and young adults.¹

Patients with Fontan physiology lack a subpulmonary ventricle and therefore experience chronically elevated systemic and hepatic venous pressures. Over time, this leads to hepatic congestion and progressive fibrosis. FALD is further exacerbated by reduced cardiac output, chronic hypoxemia, and lifestyle choices. Histologic fibrosis is nearly universal 10 years after Fontan completion; however, the severity of fibrosis does not always correlate with abnormalities in synthetic function or clinical manifestations of liver disease. As a result, patients may have advanced fibrosis or cirrhosis despite relatively preserved liver function tests.^1,2

Determining which Fontan patients should undergo heart transplantation alone versus CHLT remains challenging, and no consensus guidelines currently exist.² Liver biopsy remains the gold standard for assessing fibrosis and cirrhosis, although it may underestimate the degree of fibrosis in up to 40% of patients.¹ Several risk stratification tools have been proposed to aid clinical decision-making:

• The VAST score (Varices, Ascites, Splenomegaly, Thrombocytopenia) evaluates manifestations of portal hypertension. Patient with a score ≥2 have a nine-fold increased risk of a major adverse event defined as death, need for transplantation, or development of hepatocellular carcinoma.¹
• The MELD-XI score which excludes INR and is therefore more useful in anticoagulated Fontan patients. The Pediatric Heart Transplantation Society (PHTS) database shows a score >11.5 predicts worse survival following heart transplantation alone.¹
• The FALD score assigns one point each for cirrhosis on biopsy or imaging, varices, splenomegaly and history of ≥2 paracenteses for ascites. A score of ≥2 has been associated with worse outcomes after heart transplantation alone.^3,4

In the United States, candidates listed for CHLT are prioritized according to heart transplant allocation criteria, with the liver allocated as a “follow along” from the same donor. Consequently, waitlist times are generally similar between CHLT and heart transplantation alone candidates.^1,3

Data from the FOSTER (Fontan Outcomes Study to Improve Transplant Experience and Results) registry, which collects data from 17 centers in North America, demonstrated no significant difference in early or 1-year survival between CHLT and heart transplantation alone, although outcomes favored CHLT. Importantly, matched analyses demonstrated significantly improved 5-year survival in CHLT recipients (86%) compared with heart transplantation alone (52%, p=0.041).⁴ One proposed explanation for this survival advantage is the immunoprotective effect of the liver allograft. Combined liver transplantation appears to reduce donor-specific antibodies resulting in lower rates of cardiac allograft rejection compared with heart transplantation alone.^1,4Therefore, among the answer choices, lower rates of allograft rejection is the best answer.

REFERENCES

1. Lee JTC, Sarode D, Emamaullee JA. Review of pediatric combined heart-liver transplantation: A roadmap to success. Pediatr Transplant. 2023;27(8):e14633. doi:10.1111/petr.14633

2. Rychik J, Atz AM, Celermajer DS, et al. Evaluation and Management of the Child and Adult With Fontan Circulation: A Scientific Statement From the American Heart Association. Circulation. 2019;140(6):e234-e284. doi:10.1161/CIR.0000000000000696

3. Van Loon K, Rega F, Pirenne J, et al. Anesthesia for Combined Heart-Liver Transplantation: A Narrative Review. J Cardiothorac Vasc Anesth. 2024;38(9):2059-2069. doi:10.1053/j.jvca.2024.03.036

4. Lewis MJ, Reardon LC, Aboulhosn J, et al. Clinical Outcomes of Adult Fontan-Associated Liver Disease and Combined Heart-Liver Transplantation. J Am Coll Cardiol. 2023;81(22):2149-2160. doi:10.1016/j.jacc.2023.03.421