The Molecular and Cellular Underpinnings of Cirrhosis of the Liver

Abstract

Cirrhosis is among the leading causes of death worldwide, making up 3.5% of global deaths. It is characterized by the replacement of the liver parenchyma with fibrotic tissue and progressively leads to complete failure of the organ. It is classified into 2 types – compensated and decompensated based on the complications such as esophageal varices, hepatic encephalopathy, asterixis, and ascites. The 2 main contributors of the disease include infection and alcohol use and these, in turn, affect 4 main cell types- Hepatic Stellate Cells, Hepatocytes, LSECs, Kupffer Cells. Commonly observed in patients with cirrhosis, stellate cells are characterized by a change in phenotype often seen in wound healing mechanisms and high proliferation whereas the apoptosis of hepatocytes is a key feature leading to inflammation. The polarization of Kupffer Cells leading to the secretion of proinflammatory cytokines is another key cause of cirrhosis and the change from a fenestrated to a smooth, capillarized phenotype is observed in Sinusoidal Endothelial Cells. The role of cirrhosis on the immunology of the liver is another important topic where changes in the concentration of complement proteins, cytokines can affect the number of dendritic cells and in turn, cause pro- and anti-inflammatory responses. Modern treatment for cirrhosis has been shaped based on these cells, complications, and molecules. In this review, we shall discuss all these topics in greater detail along with interesting ideas such as the reversibility of fibrosis as well as the future research on treatments, based on the current findings.