Cardiac Biomarkers in Cirrhosis and Portal Hypertension: Relation to Circulatory and Cardiac Dysfunction

Abstract

Liver cirrhosis is a chronic disease often characterized by pronounced hemodynamic alterations affecting both the systemic and the splanchnic circulation. These circulatory changes lead to the development of extrahepatic complications involving numerous organ systems as a multi-organ failure syndrome. In the heart, alterations of the cardiac function are frequently reported with a decrease in cardiac performance and the systolic and diastolic function, which may contribute to other complications such as renal failure. The circulatory changes activate potent counter-regulatory neurohumoral mechanisms including the renin-angiotensin-aldosterone, the sympatho-adrenergic, and the vasopressin systems. Additionally, several vasoactive substances are involved in the pathogenesis of the circulatory and cardiac dysfunction in cirrhosis, and within the recent years our knowledge on the role of natriuretic peptides, cardiac troponin, endothelins, calcitonin gene-related peptide, adrenomedullin, and nitric oxide has improved considerably. Furthermore, activated cytokines such as IL-6 and TNF-α seem to aggravate the circulatory dysfunction. Cardiovascular markers have been related to both morbidity and mortality in advanced cirrhosis and may therefore serve as important prognostic markers.

Definitions

Ascites

Ascites constitutes the formation of fluid in the abdominal cavity. It is a common complication in cirrhosis occurring due to the profound circulatory changes in these patients.

Bacterial translocation

Bacterial translocation is defined as an increased intestinal permeability that facilitates the movement of bacteria from the gastrointestinal tract to mesenterial lymph nodes in patients with cirrhosis.

Cirrhosis

Cirrhosis is a chronic liver disease with progressive loss of the normal architecture of the liver tissue due to increasing fibrosis and scar tissue generation. The etiology of the disease is viral hepatitis worldwide; however, excessive alcohol intake is the most common cause in Western countries.

Cirrhotic cardiomyopathy

A specific type of cardiac dysfunction seen in patients with cirrhosis. Cirrhotic cardiomyopathy encompasses an impaired systolic function in response to circulatory stress and/or altered diastolic relaxation of the heart together with electrophysiological changes in the absence of other known cardiac disease.

Hepatic encephalopathy

Hepatic encephalopathy constitutes an altered level of consciousness or coma occurring as a result of liver failure. When the liver function deteriorates, toxic substances including ammonium are not cleared from the circulation resulting in increased concentrations passing the blood-brain barrier.

HRS

The hepatorenal syndrome is a specific type of renal failure occurring in patients with advanced cirrhosis. Infections and cardiac dysfunction seem to precipitate the development of this severe complication, which, if untreated, has a high mortality.

Hyperdynamic circulation

The hyperdynamic circulation is defined by an increased heart rate, cardiac output, and plasma volume together with a reduced arterial blood pressure and systemic vascular resistance. These changes occur in patients with advanced cirrhosis due to portal hypertension and vasodilatation.

Portal hypertension

The portal vein delivers blood from the gastrointestinal tract back to the central circulation through the liver. The pressure in the portal vein increases as the amount of fibrosis and scar tissue in the liver increases, thereby increasing the resistance in the liver. Therefore, patients with advanced cirrhosis develop portal hypertension. The pressure in the portal vein can be assessed by liver vein catheterization, and a hepatic venous pressure gradient >5 mmHg designates portal hypertension.

RAAS

The renin-angiotensin-aldosterone system is a hormonal system, which operates in order to secure sufficient blood flow to all vital organs of the body. The system is activated by sensors in the central blood vessels in case of low central blood pressure, and if activated the system induces vasoconstriction and sodium-water retention in the kidneys.

SBP

Spontaneous bacterial peritonitis designates the development of infection in the abdominal cavity despite the absence of any obvious source of infection. Cirrhotic patients with ascites or variceal bleeding are prone to develop this type of infection.