Reply.

Abstract

Potential conflict of interest: Nothing to report. Reply: I thank Drs. Arrive and Mouhadi for their letter expressing interest in my commentary on the lymphatic system in the liver that appeared in the September issue1 and for sharing their clinical observations of dilated hepatic lymphatic vessels in patients with portal hypertension using noncontrast, heavily T2‐weighted, three‐dimensional magnetic resonance imaging. Clinical observations of lymphatic vessel changes in liver diseases are indispensable for our understanding of the hepatic lymphatic system, and Drs. Arrive and Mouhadi have highlighted a useful technique for evaluating lymphatic vessel morphology in this setting. One question that occurs to me is how the vessels shown in the figures were identified as lymphatic vessels from complex vascular networks in the liver without contrast agents. Their observations of dilated hepatic lymphatic vessels in patients with portal hypertension are interesting. Previously, increased levels of endothelial nitric oxide (NO) synthase were observed in mesenteric lymphatic vessels from rats with cirrhosis and ascites.2 Given that endothelial NO synthase is the primary source of NO (a potent vasodilator) in endothelial cells, this leads to the hypothesis that mesenteric lymphatic vessels in rats with cirrhosis are dilated as well. However, one must also consider that NO production decreases in the hepatic sinusoidal circulation in cirrhosis with portal hypertension, contributing to increased resistance to portal blood flow. These observations lead to questions as to whether NO is involved in dilation of lymphatic vessels or whether NO production differs between the sinusoidal circulation and hepatic lymphatic vessels in cirrhosis with portal hypertension. Overall, little is known about the regulation of hepatic lymphatic vessels in normal and pathological conditions.3 A combination of clinical observations using noninvasive technologies such as magnetic resonance systems and elucidation of molecular mechanisms in experimental models of liver diseases will significantly advance our understanding in this area. As far as I know, in vivo imaging technologies to identify hepatic lymphatic vessels in small animals are not currently available. Such imaging is challenging, particularly in the liver, because it requires special contrast agents that enable visualization of small lymphatic vessels with high resolution while distinguishing them from hepatic arteries and veins. These technologies are eagerly awaited.