Clinical History:
- A 40-year-old woman was told that she had "hepatitis" when she recently tried to donate blood. She is asymptomatic and denies intravenous drug abuse or any known exposure to individuals with hepatitis. On laboratory testing, the hepatitis C antibody test is positive, and her serum is positive for hepatitis C viral RNA by PCR. Her hepatitis A IgG and IgM are negative. Tests for hepatitis B are negative. A liver biopsy is performed.
- What is the microscopic appearance?
Hepatitis. Image 8.1 shows a high stage with extensive fibrosis and
progression to macronodular cirrhosis, as evidenced by the large regenerative nodule. In images 8.2 through 8.3 extensive inflammation are prominent, and there is some steatosis as well (steatosis is not a usual feature of hepatitis B).
- What is the significance of these findings?
The extent of the liver injury suggests a high stage (fibrosis progressing to cirrhosis) and high grade (significant inflammation). The older terminology with chronic persistent hepatitis (CPH) and chronic active hepatitis (CAH) have largely been abandoned. We now ascribe an etiology for the liver disease and then grade (degree of inflammation) and stage (degree of fibrosis) on a scale of 1 to 4+. A lower grade and stage with hepatitis B suggest that progression to cirrhosis is less likely. However, even mild changes with hepatitis C do not guarantee that cirrhosis will not occur. The presence of hepatitis C antibody is not protective either.
- What are risk factors for her disease?
In many cases (a third to a half) there is no obvious risk factor. Risk factors in some cases of hepatitis C and are the same as those for hepatitis B, because both are spread parenterally. Unlike hepatitis B, there is usually no acute episode associated with hepatitis C, and there is a greater tendency for hepatitis C to become chronic.
- What are complications of this disease?
In about 85% of patients, hepatitis C goes on to chronic liver disease. About 15% of cases resolve. Fulminant hepatitis is quite rare. The fibrosis can proceed to a macronodular cirrhosis. In this setting, the risk for hepatocellular carcinoma is increased.
- What treatment is available for this disease?
Peginterferon alfa-2b with or without ribavirin has been used to treat patients with hepatitis C infection. Pegylation involves attaching a large inactive molecule, polyethylene glycol, to a protein in order to reduce clearance. This longer half life allows large doses of the drug to be given once weekly. However, there is variable loss of activity of the native protein, depending on the size and site of attachment of the polyethylene glycol molecule. Pegylated interferon alone is about twice as effective as monotherapy with interferon, but it is not as effective as a combination of standard interferon and ribavirin. Combining pegylated interferon and oral ribavirin improves antiviral activity and results in sustained eradication of hepatitis C virus in about half of treated patients.
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