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Interferon is produced by the body's cells in response to viral hepatitis
and other infections. There are three types--alpha, beta and gamma.
All are proteins. Commercial alpha interferon mixtures consist of the
types of interferon produced by the body. Interferon alpha-2b is the
only commercial form approved by the U.S. Food and Drug Administration
for the treatment of hepatitis B and C. However, other forms of alpha
interferon (interferon alpha-2a, lymphoblastoid or "natural"
interferon and "consensus" interferon) are being evaluated.
Interferons stimulate the body's immune system to fight viral infections
and affect the ability of viruses to divide in liver cells. Patients
with chronic hepatitis B or C infections also appear to be unable to
produce normal amounts of interferon. Less
than 50 percent of patients with chronic hepatitis B infection are eligible
for interferon therapy. Patients should have infection documented for
at least six months, elevated liver enzymes (AST or SGOT, and ALT or
SGPT tests) and an actively dividing virus in their blood (hepatitis
"e" antigen (HBeAg) and/or hepatitis B virus DNA (HBV DNA)
positive tests). Patients with normal liver enzymes are less likely
to respond to therapy. Patients with low hepatitis B virus DNA levels
and elevated liver enzymes are more likely to benefit than those with
high HBV DNA levels. A biopsy, where a needle is inserted into the liver
to obtain a small sample of tissue, is helpful to determine liver damage
prior to treatment. Patients with acute infection, cirrhosis or other
major medical problems should not be treated. Patients
with elevated liver enzymes for six or more months and who have a detectable
antibody (ELISA test) to hepatitis C (anti-HCV) are eligible for therapy.
Patients who have a risk factor for hepatitis C (blood transfusion,
needle-stick exposure or illegal intravenous drug use) need not have
the hepatitis C result confirmed by additional testing. However, patients
without such a risk factor should have a second test (RIBA test). Liver
biopsy is helpful in the diagnosis of viral hepatitis, assessing liver
damage prior to treatment, and at the end of therapy to evaluate the
response. Patients with acute infection, complications from cirrhosis,
other major medical problems and autoimmune liver disease should not
be treated with interferon. The
standard approved dose for hepatitis C is three million units, three
times weekly for 24 weeks. Approved treatment for hepatitis B is five
million units daily for 16 weeks. Treatment may be modified for significant
side effects. However, lower doses may result in lower rates of response.
Higher doses or longer therapy are being tested. The
most common serious side effect is depression, particularly in patients
with a prior history. Most patients will have muscle aches, fatigue
and low grade fevers. These can be minimized by taking low doses of
acetaminophen (e.g. Tylenol) at night. Nausea and diarrhea are common
as is irritation of the skin at the injection site. Patients may experience
significant weight loss, and if this occurs the dose should be adjusted.
Patients often complain of irritability and headaches. A small number
of patients may develop thyroid disease. Normal thyroid function should
be documented prior to treatment. Hair loss is not uncommon, but usually
reversible. Few side effects are severe or persist after treatment.
Patients
with chronic hepatitis B or C, with fluid in the abdomen (ascites),
bleeding from dilated veins in the esophagus (variceal bleeding), or
mental confusion (encephalopathy) should be treated only in a clinical
trial. Others not suitable for treatment are those with symptomatic
heart, lung or kidney disease, with human immunodeficiency virus (HIV)
infection or organ transplant recipients on prednisone, cyclosporine
and FK-506 and patients on antidepressants or with a history of suicide
attempts. Interferon should not be given to women considering pregnancy,
nor to the intended father. Patients with active substance abuse (alcohol
or illegal drugs) should not be offered this therapy. Approximately 40-50 percent of patients with chronic hepatitis C receiving full dose therapy will have a normalization of their liver enzymes, usually by the third month. With normal liver tests, the virus may become undetectable in blood. If no response is seen by three months, most researchers advocate stopping therapy. A few patients who respond to therapy may see their liver enzymes rise towards the end of treatment. The reason for this is unknown. When interferon is stopped after six months, more than half of the patients with hepatitis C who have responded will experience a rise in their liver tests. Patients will usually respond again if given further therapy. Therefore, 10-15 percent will have a long lasting positive response. Longer treatments will likely result in longer positive responses. However, there is no evidence that this affects the relapse rate when treatment is stopped. Few patients will eradicate the virus. A
positive response to treatment for hepatitis B occurs in about 35 percent
of patients. This is usually associated with a normalization of liver
enzymes, and a loss of three "markers" for an active infection.
These markers are hepatitis "e" antigen (HBeAg), hepatitis
B DNA (indicating that the virus is reproducing) and hepatitis B surface
antigen (HBsAg). An estimated 6 to 20 percent of patients lose these
markers after therapy is stopped. A positive response to therapy is
preceded by a rise in liver enzymes. Why this happens is not understood.
Complete elimination of the virus is seldom achieved. The long term prognosis of hepatitis C is poorly understood. However, hepatitis C is generally a slowly progressive disease, with evolution over years if not decades. There is no proof that six months of treatment with interferon alters this. The changes vary from mild chronic hepatitis (least amount of liver damage) to moderate or severely active chronic hepatitis, with or without fibrosis or cirrhosis (most amount of liver scar damage). It is not known who will develop complications of chronic liver disease and liver failure. In
contrast, hepatitis B tends to progress more rapidly over years, although
occasionally over decades. Not all patients with either hepatitis B
or C will develop complications of liver disease. However, for hepatitis
B, interferon should be considered strongly in eligible patients. In
addition, patients with chronic hepatitis B are less than ideal candidates
for transplantation because of damage to the new liver. Patients transplanted
for hepatitis B or C will usually see a recurrence of the viruses. Much
is unknown about treatment with interferon. Therefore, when possible,
patients should consider participating in clinical trials. Different
kinds of interferons and other new drugs, by themselves or in combination
with other drugs, are being evaluated for both hepatitis B and C.
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