Liver Fibrosis

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Liver Fibrosis

Reviewed 7/15/05 by V. J. , RN, BSN,

MA

When infected by the hepatitis C virus, liver cells (hepatocytes) trigger a series of events that initiate both an inflammatory and an immune response.

Since hepatitis C infection tends to become chronic in most

cases, the inflammatory process in turn progresses from acute to chronic inflammation. In time, chronic inflammation leads to the formation of microscopic areas of scar tissue in the liver tissue, known

as fibrosis.

If the scar tissue causes disruption in the structure of the liver, the condition is called cirrhosis.

In its early stages, fibrosis is reversible, but cirrhosis, once developed, may be permanent.

In this article, we will provide an overview of some of the

mechanisms of fibrosis as well as factors that contribute to the progression of fibrosis to cirrhosis.

The Key Players: Stellate and Kupffer

Cells

Hepatic Stellate Cells. Under normal conditions, stellate ("star-shaped" ) cells are reservoirs of fat and vitamin A in the liver. They also contain filaments that can contract and regulate blood

flow through the liver.

When activated by liver damage and the chemical by-products

of inflammation, stellate cells transform and become capable of creating strands of collagen, a substance fundamental to the formation of scar tissue. These collagen strands are deposited in areas of inflammation in an effort to contain the spread of viral infection.

Kupffer Cells. Kupffer cells are specialized leukocytes (white blood cells) in the liver. They can move rapidly around the liver, and are responsible for the removal of particulate matter from the circulating blood, such as old or damaged red blood cells, bacteria,

viruses, parasites and tumor cells.

When leukocytes from outside the liver are drawn to the area of infection by chemical signals called cytokines released by infected liver cells, they cooperate with Kupffer cells to produce chemical signals that cause stellate cells to begin producing collagen fibers.

In addition, Kupffer cells produce oxygen free-radicals. As we shall see, oxygen free-radicals play a major role in the progression and development of fibrosis.

The Pathophysiology of Fibrosis

The deposition of collagen in an area of injury is not an abnormal event. By attempting to enclose an injured or infected area with scar tissue, the body attempts to limit the spread of infection to other cells.

Normally, as an infection or injury resolves, the collagen matrix enclosing the injury is dissolved as activated stellate cells die

off, allowing the tissue to return to normal.

Unfortunately, in a chronic illness such as hepatitis C infection, ongoing infection and inflammation causes the collagen matrix

to grow more rapidly than it can be dissolved. The result is a surplus of scar tissue, which can eventually progress to cirrhosis.

The deposition of collagen has direct effects on liver function, specifically:

The presence of collagen fibers around individual hepatocytes impair the cells' ability to receive nutrition and results in shrinkage of the cell (hepatocellular atrophy).

The accumulation of collagen fibers in the hepatic sinusoids (microscopic blood channels in the liver) obstructs the passage of substances from the blood to the hepatocytes, decreasing the liver's ability to remove drugs, toxins and metabolic waste products.

Fibrosis around the veins of the liver restricts blood flow, increasing vascular resistance and contributing to the development

of portal hypertension. Portal hypertension, in turn, contributes to the development of esophageal varices, edema and ascites.

Impaired blood flow through the liver forces arterial blood to bypass the filtering cells of the liver, further decreasing the

efficiency of the liver and contributing to the death of hepatic cells.

The Assessment of Fibrosis

Normally, a liver biopsy

is performed to accurately assess the progression of fibrosis in liver disease. The following terms are often used to describe the changes in

liver tissue associated with HCV infection:

Portal Inflammation: the portal areas are tiny tracts of connective tissue within the liver that contain branches of the portal vein, the hepatic artery and bile ducts.

Piecemeal Necrosis: this term describes necrosis (cellular death) and inflammation around the portal areas.

Fibrosis: the deposition of collagen fibers in the cell

structure of the liver, forming scar tissue. The early stages of fibrosis are confined to the portal tracts.

Bridging Fibrosis: an intermediate stage of fibrosis characterized by expansion of collagenous (scar) tissue to the portal tracts and bridging between portal areas.

Cirrhosis: a term used to describe significant deformation of the liver structure due to scarring.The problem with the gene pool? No lifeguards!