Author + information
- Maxim Itkin, MD∗ (, )
- Jack Rychik, MD and
- David A. Piccoli, MD
- ↵∗Center for Lymphatic Imaging and Interventions, Children’s Hospital of Philadelphia/Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104
We appreciate the interest of Dr. Dam and colleagues in our work (1) and their thoughtful comments.
The main goal of our study was to describe the pathophysiological mechanism of loss of protein in patients with Fontan physiology complicated by protein-losing enteropathy (PLE). Using the technique of liver lymphangiography, we discovered significant leakage of protein-rich liver lymph into the duodenum, a unique finding not previously appreciated, and a potential area for therapeutic intervention.
The primary goal of embolization of the liver lymphatic ducts in our study was the improvement of patients’ symptoms and quality of life, which we demonstrated as being concomitant with a temporally associated increase in serum albumin levels. Serum albumin is recognized as an important marker of disease severity in Fontan PLE, with multiple studies using this measure as an acceptable surrogate ranging from looking at the epidemiology of the condition to treatment responses and end-organ consequences (2–4). In essence, PLE correlates directly with hypoalbuminemia—and any management strategy that improves albumin levels is considered therapeutic. We can only hope that liver lymphatic embolization with a sustained increase in serum albumin levels will increase patients’ survival as well; however, only longer-term studies can answer this question. Nevertheless, even temporary reversal of PLE with improved albumin levels can potentially improve the status of such patients by reducing the complications and frailty related to chronic albumin loss.
We agree with Dr. Dam and colleagues that serum albumin level and symptoms can fluctuate. However, in patients P4, P5, and P7 the initial improvement of symptoms and the albumin level increase persist and is sustained to the date of this letter. This is not a random variation phenomenon. The follow-up is now close to 1 year, and we believe we can now refer to the outcome of liver lymphatic embolization treatment as a remission (but not yet a cure).
Lymphangiectasia is a frequent finding in a variety of diseases, including celiac disease, as mentioned. Screening for celiac might be interesting, but statistically would not identify common positivity, and only a very rare celiac has significant protein loss, and not to this magnitude.
In conclusion, we continue to investigate the importance of the liver lymphatic circulation in patients with right-sided heart failure and its contribution to the development of PLE in those with a Fontan circulation. Our hope is that, by identifying the mechanism for protein loss (as we have achieved) and further developing these interventional techniques, we can improve the quality and quantity of life for these patients.
Please note: Dr. Itkin has received a research grant from Guerbet Villepinte, France, manufacturer of contrast agent, lipiodol. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.