Lymphatic dysfunction in advanced cirrhosis: Contextual perspective and clinical implications

Abstract

The lymphatic system plays a very important role in body fluid homeostasis, adaptive immunity, and the transportation of lipid and waste products. In patients with liver cirrhosis, capillary filtration markedly increases, primarily due to a rise in hydrostatic pressure, leading to enhanced production of lymph. Initially, lymphatic vasculature expansion helps to prevent fluid from accumulating by returning it back to the systemic circulation. However, the lymphatic functions become compromised with the progression of cirrhosis and, consequently, the lymphatic compensatory mechanism gets overwhelmed, contributing to the development and eventual worsening of ascites and edema. Neurohormonal changes, low-grade chronic inflammation, and compounding effects of predisposing factors such as old age, obesity, and metabolic syndrome appear to play a significant role in the lymphatic dysfunction of cirrhosis. Sustained portal hypertension can contribute to the development of intestinal lymphangiectasia, which may rupture into the intestinal lumen, resulting in the loss of protein, chylomicrons, and lymphocyte, with many clinical consequences. Rarely, due to high pressure, the rupture of the subserosal lymphatics into the abdomen results in the formation of chylous ascites. Despite being highly significant, lymphatic dysfunctions in cirrhosis have largely been ignored; its mechanistic pathogenesis and clinical implications have not been studied in depth. No recommendation exists for the diagnostic evaluation and therapeutic strategies, with respect to lymphatic dysfunction in patients with cirrhosis. This article discusses the perspectives and clinical implications, and provides insights into the management strategies for lymphatic dysfunction in patients with cirrhosis.

Keywords: Lymphatic dysfunction; Cirrhosis; Lymphedema; Lymphangiectasia; Chylous ascites; Refractory ascites

Core Tip: Lymphatic dysfunction appears to play a significant role in the pathophysiology of advanced cirrhosis. Sustained portal hypertension, neurohormonal changes, and low-grade chronic inflammation have been implicated in causing lymphatic dysfunction in advanced cirrhosis, leading to worsening of ascites, lymphedema, and abnormal lipid transport; it also results in increased susceptibility to infections. Chylous ascites and intestinal lymphangiectasia are the rare manifestations of lymphatic dysfunction in cirrhosis, leading to loss of protein, fat, lymphocytes, and immunoglobins, with several clinical consequences. Lymphatic dysfunctions in cirrhosis have been ignored to date; hence, new exploratory research must be undertaken to gain insight into this important subject.