Cirrhosis is a condition that is defined histopathologically and has a variety of clinical manifestations and complications, some of which can be life-threatening. In the past, it has been thought that cirrhosis was never reversible; however, it has become apparent that when the underlying insult that has caused the cirrhosis has been removed, there can be reversal of fibrosis. This is most apparent with the successful treatment of chronic hepatitis C; however, reversal of fibrosis is also seen in patients with hemochromatosis who have been successfully treated and in patients with alcoholic liver disease who have discontinued alcohol use.
Regardless of the cause of cirrhosis, the pathologic features consist of the development of fibrosis to the point that there is architectural distortion with the formation of regenerative nodules. This results in a decrease in hepatocellular mass, and thus function, and an alteration of blood flow. The induction of fibrosis occurs with activation of hepatic stellate cells, resulting in the formation of increased amounts of collagen and other components of the extracellular matrix.
Clinical features of cirrhosis are the result of pathologic changes and mirror the severity of the liver disease. Most hepatic pathologists provide an assessment of grading and staging when evaluating liver biopsy samples. These grading and staging schemes vary between disease states and have been developed for most conditions, including chronic viral hepatitis, nonalcoholic fatty liver disease, and primary biliary cholangitis. Advanced fibrosis usually includes bridging fibrosis with nodularity designated as stage 3 and cirrhosis designated as stage 4. Patients who have cirrhosis have varying degrees of compensated liver function, and clinicians need to differentiate between those who have stable, compensated cirrhosis and those who have decompensated cirrhosis. Patients who have developed complications of their liver disease and have become decompensated should be considered for liver transplantation. Many of the complications of cirrhosis will require specific therapy. Portal hypertension is a significant complicating feature of decompensated cirrhosis and is responsible for the development of ascites and bleeding from esophagogastric varices, two complications that signify decompensated cirrhosis. Loss of hepatocellular function results in jaundice, coagulation disorders, and hypoalbuminemia and contributes to the causes of portosystemic encephalopathy. The complications of cirrhosis are basically the same regardless of the etiology. Nonetheless, it is useful to classify patients by the cause of their liver disease (Table 337-1); patients can be divided into broad groups with alcoholic cirrhosis, cirrhosis due to chronic viral hepatitis, biliary cirrhosis, and other, less common causes such as cardiac cirrhosis, cryptogenic cirrhosis, and other miscellaneous causes.
TABLE 337-1Causes of Cirrhosis ||Download (.pdf) TABLE 337-1 Causes of Cirrhosis
|Alcoholism ||Cardiac cirrhosis |
|Chronic viral hepatitis ||Inherited metabolic liver disease |
| Hepatitis B || Hemochromatosis |
| Hepatitis C || Wilson’s disease |
|Autoimmune hepatitis || α1 Antitrypsin deficiency |
|Nonalcoholic steatohepatitis || Cystic fibrosis |
|Biliary cirrhosis ||Cryptogenic cirrhosis |
| Primary biliary cholangitis || |
| Primary sclerosing cholangitis || |
| Autoimmune cholangiopathy || |