Reviewed By: Pramod Kerkar, MD, FFARCSI

Liver fibrosis is an excessive scarring of a wound, in which connective tissue accumulates in the liver. In this situation, the extracellular matrix is produced excessively, degraded poorly or both situations occur. The trigger is chronic injury, especially in the presence of an inflammatory component. Fibrosis itself does not cause symptoms, but it can cause portal hypertension (scarring distorts blood flow through the liver) or cirrhosis (scarring affects normal liver structure and causes liver dysfunction). The diagnosis is based on liver biopsy. The treatment consists of correcting the underlying disorder, whenever possible.

In liver fibrosis, excessive connective tissue accumulates in the liver; this tissue represents scarring in response to repetitive chronic liver cell injury. Frequently, fibrosis progresses and compromises the structure and then the function of the liver, as hepatocytes undergoing regeneration attempt to replace and repair damaged tissue. When this disorder is disseminated, cirrhosis is confirmed.

Several types of chronic liver injury can cause fibrosis. Acute, self-limiting hepatic injury (for example, acute viral hepatitis A), even if it is fulminating, does not necessarily distort the basic structure of the liver and, therefore, does not promote the development of fibrosis despite the loss of hepatocytes. In its early stages, liver fibrosis may regress if the cause is reversible (e.g., after virus clearance). If the patient is exposed to several months or years of chronic or repetitive injury, fibrosis becomes permanent. Fibrosis develops at an even greater rate in the presence of mechanical obstruction of the bile ducts.

What Causes Liver Fibrosis?

The activation of the perivascular stellate liver cells (Ito cells, which store lipids) promotes the development of fibrosis. These and adjacent cells proliferate and become contractile cells called myofibroblasts, which produce excessive amounts of abnormal matrix (formed by collagen, other glycoproteins and glucans) and cellular matrix proteins. Kupffer cells (resident macrophages), injured hepatocytes, platelets and leukocytes are added. As a consequence, reactive O2 species and inflammatory mediators are released (eg, platelet-derived growth factor, transforming growth factors, connective tissue growth factor). Consequently, the activation of the stellate cells promotes the development of an abnormal extracellular matrix, both in the quantity and composition.

The myofibroblasts stimulated by endothelin-1 contribute to increase the resistance in the portal vein and increase the density of the abnormal matrix. The fibrous tracts are united with branches of the afferent veins and efferent hepatic veins, which allows them to skip the hepatocytes and limits their blood supply. Therefore, fibrosis contributes both to hepatocyte ischemia (with subsequent hepatocellular dysfunction) and to portal hypertension. The magnitude of ischemia and portal hypertension determines the hepatic condition. For example, congenital hepatic fibrosis compromises the branches of the portal vein and almost does not affect the parenchyma. As a result, portal hypertension develops, but with normal hepatocellular function.

What are the Signs and Symptoms of Liver Fibrosis?

Hepatic fibrosis itself does not cause symptoms. These can result from the disorder that causes fibrosis or, once fibrosis progresses to cirrhosis, from complications of portal hypertension. These symptoms include bleeding from varicose veins, ascites (accumulation of fluid in the abdominal cavity), and portosystemic encephalopathy. Cirrhosis can result in liver failure and potentially lethal liver failure.

How is Liver Fibrosis Diagnosed?

  • Clinical evaluation
  • Blood tests and/or diagnostic tests by non-invasive images
  • Liver biopsy

Liver fibrosis is suspected if patients have known chronic liver disease (eg, chronic viral hepatitis C and hepatitis B or alcoholic liver disease), if the results of liver function tests are abnormal; in such cases, tests are performed to check for fibrosis and, if fibrosis is present, to determine its severity (stage). The knowledge of the stage of fibrosis can guide medical decisions.

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Pramod Kerkar

Written, Edited or Reviewed By:


Pain Assist Inc.

Last Modified On: June 1, 2018

This article does not provide medical advice. See disclaimer

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