The interplay between lymphatic system and portal hypertension: a comprehensive review

The pathophysiology of portal hypertension revolves around numerous structural and functional changes in the intra- and extra-hepatic vascular compartments. In recent years, a dysfunction of the lymphatic system has garnered increasing attention as one of the key sequelae of portal hypertension.

The review comprehensively deliberates about the anatomical and functional attributes of the hepatic lymphatic system during portal hypertension. Along with liver lymphatic system, important modifications that occur in extrahepatic lymphatics during advanced liver disease are discussed.

During progression of liver disease, elevated portal pressures cause increased sinusoidal blood and enhanced lymph flow, leading to dilation and proliferation of hepatic lymphatic vessels. In advanced liver disease, portal and central lymphatic systems also undergo profound changes to accommodate increased lymph flows. These changes in lymphatic system seem to have evolved as compensatory mechanisms to alleviate enhanced portal pressures. However, further increase in the splanchnic lymph production causes a complete failure of the drainage capacity of local and central lymphatic vessels, leading to maldistribution of extracellular fluid along with immune system anomalies aggravating ascites and pathological bacterial translocation.

Lymphatic dysfunction plays a crucial role in the progression and complications of portal hypertension. Development of routine imaging techniques for lymphatic vessels in clinics,  protocols for measuring lymphovenous pressure gradient and in vitro and in vivo experimental studies are requisite to further our understanding in this field. Targeting lymphatic dysfunction could offer promising therapeutic options for managing cirrhosis, portal hypertension and related complications.