Extrahepatic complications to cirrhosis and portal hypertension: Haemodynamic and homeostatic aspects

Abstract

In addition to complications relating to the liver, patients with cirrhosis and portal hypertension develop extrahepatic functional disturbances of multiple organ systems. This can be considered a multiple organ failure that involves the heart, lungs, kidneys, the immune systems, and other organ systems. Progressive fibrosis of the liver and subsequent metabolic impairment leads to a systemic and splanchnic arteriolar vasodilatation. This affects both the haemodynamic and functional homeostasis of many organs and largely determines the course of the disease. With the progression of the disease, the circulation becomes hyperdynamic with cardiac, pulmonary as well as renal consequences for dysfunction and reduced survival. Infections and a changed cardiac function known as cirrhotic cardiomyopathy may be involved in further aggravation of other complications such as renal failure precipitating the hepatorenal syndrome. Patients with end-stage liver disease and related complications as for example the hepatopulmonary syndrome can only radically be treated by liver transplantation. As a bridge to this treatment, knowledge on the mechanisms of the pathophysiology of complications is essential for the choice of vasoactive drugs, antibiotics, drugs with specific effects on fibrogenesis and inflammation, and drugs that target specific receptors.

Keywords: Fibrogenesis, Splanchnic haemodynamics, Inflammation, Bacterial translocation, Infections, Systemic circulation, Cirrhotic cardiomyopathy, Hepatopulmonary syndrome, Portopulmonary hypertension, Hepatorenal syndrome, Ascites

Core tip: Patients with cirrhosis develop extrahepatic functional disturbances as a multiple organ failure that involves the heart, lungs, kidneys, the immune systems, and other organ systems. Fibrosis of the liver leads to a systemic vasodilatation that affects both the homeostasis of many organ systems. The circulation becomes hyperdynamic, which is often further aggravated by infections. Changes in organ function involve the heart as a cirrhotic cardiomyopathy, the kidneys such as the hepatorenal syndrome and the lungs with development of a hepatopulmonary syndrome. Liver transplantation is often the only radical treatment and as a bridge to this treatment, knowledge on the mechanisms of the pathophysiology of complications is essential.