The Role of Lymphatics in Cholestasis: A Comprehensive Review

Cholestatic liver disease affects millions of people worldwide and stems from a plethora of causes such as immune dysfunction, genetics, cancerous growths, and lifestyle choices. While not considered a classical lymphatic organ, the liver plays a vital role in the lymph system producing up to half of the body's lymph per day. The lymphatic system is critical to the health of an organism with its networks of vessels that provide drainage for lymphatic fluid and routes for surveilling immune cells. Cholestasis results in an increase of inflammatory cytokines, growth factors, and inflammatory infiltrate. Left unchecked, further disease progression will include collagen deposition which impedes both the hepatic and lymphatic ducts, eventually resulting in an increase in hepatic decompensation, increasing portal pressures, and accumulation of fluid within the abdominal cavity (ascites). Despite the documented interplay between these vital systems, little is known about the effect of liver disease on the lymph system and its biological response. This review looks at the current cholestatic literature from the perspective of the lymphatic system and summarizes what is known about the role of the lymph system in liver pathogenesis during hepatic injury and remodeling, immune-modulating events, or variations in interstitial pressures.