Liver Cirrhosis Pathophysiology

Definition and Etiology

The most common causes of liver cirrhosis worldwide include viral hepatitis, alcohol-related liver disease, and metabolic associated steatotic liver disease, according to the International Journal of Surgery 1

Chronic liver injury initiates a wound healing response that becomes dysregulated, leading to abnormal continuation of connective tissue production and deposition, as stated in the International Journal of Surgery 1
The process of fibrosis development begins with deposition of a fine neomatrix within the space of Disse that progressively matures and enlarges over time, as reported in the Journal of Hepatology 2
Fibrosis typically starts in the centrilobular region and extends toward the portal tract as the disease progresses, according to the Journal of Hepatology 2 and 3

Increased intrahepatic resistance to portal flow is the primary factor in the development of portal hypertension, with a structural component due to fibrous tissue and vascular distortion, and a functional component due to increased intrahepatic vascular tone, as stated in Hepatology 4 and 5
Portal hypertension leads to formation of portosystemic collaterals and splanchnic vasodilation, increasing flow into the gut and portal venous system, as reported in Hepatology 4 and 5

Advanced cirrhosis is characterized by a state of chronic inflammation with increased circulating levels of pro-inflammatory cytokines and chemokines, likely caused by systemic spread of bacteria and bacterial products, as stated in the Journal of Hepatology 7
Systemic inflammation and circulatory dysfunction contribute to multi-organ failure in advanced disease, as reported in the Journal of Hepatology 7

Decompensation is characterized by development of complications including ascites, variceal hemorrhage, hepatic encephalopathy, and jaundice, as stated in Hepatology 4
The compensated stage is the longest stage and is asymptomatic, while the decompensated stage is much shorter and can rapidly progress to multi-organ failure, as reported in Hepatology 4

Portal hypertension drives the development of gastroesophageal varices, which are present in 30-40% of patients with compensated cirrhosis and up to 85% of those with decompensated cirrhosis, as stated in Hepatology 4
The risk of complications is higher in patients with Child-Pugh B and C cirrhosis and those with significant portal hypertension, as reported in the International Journal of Surgery 1