In a significant advancement for patients with Fontan-associated liver disease (FALD), a recent study published in “Digestive and Liver Disease,” the official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, has identified key biomarkers that could greatly ease the burden of liver fibrosis assessment in affected individuals.

DOI: 10.1016/j.dld.2023.12.017

The retrospective study, led by Chaowapong Jarasvaraparn of the Division of Pediatric Gastroenterology, Hepatology and Nutrition at Riley Hospital for Children and Indiana University, with colleagues Jessica Thoe, Andrew Rodenbarger, Howard Masuoka, R. Mark Payne, Larry Wayne Markham, and Jean P. Molleston, took a closer look at patients who had undergone the Fontan procedure—a surgical operation used to treat complex congenital heart defects—and subsequently experienced liver complications due to altered blood flow dynamics.

For patients who live with the repercussions of the Fontan procedure, routine assessment of liver health is crucial. Until now, liver biopsy has been the gold standard in diagnosing FALD, a method known for its invasiveness and associated risks. However, this new research, which surveyed post-Fontan patients aged 10 and older, a total of 66 individuals (55.3% adults and 68.4% children), suggests that non-invasive biomarker tests could potentially replace or reduce the need for liver biopsy.

Advanced liver disease (ALD), characterized by bridging fibrosis or cirrhosis, was found in a significant number of the study’s cohort upon biopsy. The presence of ALD was strongly associated with a set of biological markers, including low platelet counts, and elevated AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) scores. Most notably, the study concludes that APRI and FIB-4 showed modest accuracy for identifying ALD in adult patients but were less effective for children. This implies that these markers could be used to track disease progression in older post-Fontan patients.

Liver Stiffness Measurement (LSM) using FibroScan also displayed a good sensitivity of 81.3%, albeit with a specificity of 45.5% at a cut-off of 18.5kPa. Such findings suggest FibroScan might serve as a particularly useful non-invasive tool in the evaluation of liver stiffness and, subsequently, fibrosis in FALD patients.

The significance of this research cannot be understated, given the long-term implications of the Fontan procedure on patient health and the necessity for ongoing monitoring of potential liver damage. The introduction of non-invasive methods to detect ALD development in such patients marks a critical step forward in the management of FALD, bearing the potential to revolutionize the standard of care.

With its rigorous analytical method and its implications for clinical practice, Jarasvaraparn and colleagues have contributed meaningfully to the field of pediatric gastroenterology, hepatoenterology, and cardiology. The researchers also emphasize the absence of conflicts of interest, affirming the integrity and importance of their findings.

For the medical community and those living with FALD, these new insights provide hope for improved patient outcomes and quality of life, reducing the dependency on traditional invasive liver biopsies and moving towards more patient-friendly, consistent, and reliable monitoring regimes.

As this news disseminates through both the academic and clinical sectors, health professionals are poised to adopt these findings, applying them to patient care protocols and enhancing the monitoring for those impacted by Fontan-associated liver disease.

References

1. Jarasvaraparn, C., Thoe, J., Rodenbarger, A., Masuoka, H., Payne, R. M., Markham, L. W., & Molleston, J. P. (2024). Biomarkers of fibrosis and portal hypertension in Fontan-associated liver disease in children and adults. Digestive and Liver Disease. https://doi.org/10.1016/j.dld.2023.12.017
2. Rychik, J. (2016). The relentless effects of the Fontan paradox. Seminars in Thoracic and Cardiovascular Surgery: Pediatric Cardiac Surgery Annual, 19(1), 37–43. https://doi.org/10.1053/j.pcsu.2015.11.005
3. Ginde, S., Hsu, D., & Veldtman, G. (2017). Liver health in adults with Fontan circulation: A review of the literature. International Journal of Cardiology, 249, 175–182. https://doi.org/10.1016/j.ijcard.2017.08.044
4. Daniels, C. J., Bradley, E. A., Landzberg, M. J., Aboulhosn, J., Beekman III, R. H., & Book, W. (2017). Fontan-associated liver disease: Proceedings from the American College of Cardiology Stakeholders Meeting, October 1 to 2, 2016, Washington DC. Journal of the American College of Cardiology, 70(25), 3173-3194. https://doi.org/10.1016/j.jacc.2017.11.024
5. Kutty, S. S., Peng, Q., Danford, D. A., Fletcher, S. E., Perry, D., Talmon, G. A., & Scott, C. G. (2013). Increased hepatic stiffness as consequence of high hepatic afterload in the Fontan circulation: A vascular Doppler and elastography study. The Faculty of Medicine and Health, University of Leeds.

Keywords

1. Fontan-associated liver disease
2. Liver fibrosis biomarkers
3. FALD
4. Non-invasive liver assessment
5. Fontan procedure complications