Definition

Cirrhosis is a progressive and ultimately fatal syndrome of hepatic failure.

Pathophysiology

Chronic alcoholism is the most common cause of cirrhosis (Laënnec’s cirrhosis) in the United States. Cirrhosis is also caused by biliary obstruction, chronic hepatitis, right-sided heart failure, α₁-antitrypsin deficiency, Wilson disease, and hemochromatosis. Anatomic alterations secondary to hepatocyte necrosis are the primary cause of the deterioration that occurs in liver function.

Over time, the liver parenchyma is replaced by fibrous and nodular tissue, which distorts, compresses, and obstructs normal portal venous blood flow. Portal hypertension develops and impairs the ability of the liver to perform various metabolic and synthetic processes. Obstructive engorgement of vessels within the portal system ultimately results in transmission of increasing backpressure within the splanchnic circulation. Therefore, splenomegaly, esophageal varices, and right-sided heart failure ensue in addition to deterioration in liver function.

The development of esophageal varices places the patient at risk for spontaneous, severe upper gastrointestinal hemorrhage. Fluid sequestration resulting from ascites causes consequent alteration in intravascular fluid dynamics and alteration in the renin–angiotensin system. Subsequent reduction in renal perfusion results in eventual renal failure in conjunction with hepatic failure (hepatorenal syndrome). Failure of the liver to clear nitrogenous compounds (ammonia) from the blood contributes to the development of progressive mental status changes (caused by encephalopathy), ultimately leading to coma.

Clinical manifestations

The clinical manifestations of cirrhosis may not be strongly correlated with the severity of the disease process. Patients may have severe liver disease without overt jaundice and ascites. However, the eventual development of jaundice and ascites is observed in most patients as the disease process progresses. Other signs of severe liver disease include gynecomastia, spider angiomata, palmar erythema, and asterixis. Hepatic fibrosis results from the presence of other diseases; portal hypertension ensues, along with its sequelae. These diseases include Budd-Chiari syndrome (vena cava or hepatovenous obstruction), idiopathic portal fibrosis (Banti syndrome), schistosomiasis, and certain rare congenital fibrotic disorders. Venous occlusive disease secondary to metastases, primary hepatic neoplasia, or thromboembolism is also associated with portal hypertension.