| HCV-positive
patients should be evaluated for the
presence and severity of chronic liver disease. Initial evaluation for presence of disease should
include multiple measurements of ALT at regular
intervals, because ALT activity fluctuates in persons
with chronic hepatitis C. Patients with chronic
hepatitis C should be evaluated for the severity
of their liver disease and for possible treatment. Antiviral therapy is recommended for patients with
chronic hepatitis C who are at greatest risk for
progression to cirrhosis. These persons include anti-HCV-positive patients with persistently elevated
ALT levels, detectable HCV RNA, and a liver biopsy
that indicates either portal or bridging fibrosis or at
least moderate degrees of inflammation and necrosis.
In patients with less severe histologic changes,
indications for treatment are less clear, and careful
clinical follow-up might be an acceptable alternative
to treatment with antiviral therapy (e.g., interferon) because progression to cirrhosis is
likely to be slow,
if it occurs at all. Similarly, patients with compensated cirrhosis (without
jaundice, ascites, variceal
hemorrhage, or encephalopathy) might not benefit
from interferon therapy. Careful assessment should
be made, and the risks and benefits of therapy should
be thoroughly discussed with the patient.
Patients with persistently normal ALT values should
not be treated outside of clinical trials, as treatment
might actually induce liver enzyme abnormalities. Patients with advanced cirrhosis who
might be at
risk for decompensation with therapy and pregnant
women also should not be treated. Interferon
treatment is not FDA-approved for patients aged
<18 years or >60 years. Treatment of patients who
are drinking excessive amounts of alcohol or who are injecting illegal drugs should be
delayed until these behaviors have been discontinued for > 6 months.
Contraindications to treatment with interferon
include major depressive illness, cytopenias, hyperthyroidism, renal transplantation, and
evidence of autoimmune disease.
Most clinical trials of treatment for chronic hepatitis
C have been conducted using alpha interferon. When
the recommended regimen of 3 million units
administered subcutaneously 3 times/week for 12
months is used, approximately 50% of treated patients have normalization of serum ALT
activity
(biochemical response), and 33% have a loss of
detectable HCV RNA in serum (virologic response)
at the end of therapy. However, > 50% of these
patients relapse when therapy is stopped. Thus,
15%-25% have a sustained response as measured by testing for ALT and HCV RNA > 1
years after
therapy is stopped, many of whom also have
histologic improvement. For patients who do not
respond by the end of therapy, retreatment with a standard dose of interferon is rarely
effective. Patients who have persistently abnormal ALT levels
and detectable HCV RNA in serum after 3 months of interferon are unlikely to respond to
treatment, and interferon treatment should be discontinued. These persons might be
considered for participation in
clinical trials of alternative treatments. Decreased interferon response rates (<15%)
have been found in patients with higher serum HCV RNA titers and
HCV genotype 1 (the most common strain of HCV
in the United States); however, treatment should not
be withheld based solely on these findings.
Therapy for hepatitis C is a rapidly changing area of
clinical practice. Combination therapy with interferon
and ribavirin, a nucleoside analogue, is approved for
the naive treatment of patients with chronic hepatitis
C. Studies of patients treated with a combination of ribavirin and interferon have
demonstrated a
substantial increase in sustained response rates,
reaching 40%-50%, compared with response rates of 15%-25% with interferon alone. However,
as with interferon alone, combination therapy in patients
with genotype 1 is not as successful, and sustained response rates among these patients
are still <30%.
Most patients receiving interferon experience flu-
like symptoms early in treatment, but these
symptoms diminish with continued treatment.
Later side effects include fatigue, bone marrow
suppression, and neuropsychiatric effects
(e.g., apathy, cognitive changes, irritability, and
depression). Interferon dosage must be reduced in
10%-40% of patients and discontinued in 5%-15%
because of severe side effects. Ribavirin can induce
hemolytic anemia and can be problematic for patients
with pre-existing anemia, bone marrow suppression,
or renal failure. In these patients, combination
therapy should be avoided or attempts should be
made to correct the anemia. Hemolytic anemia
caused by ribavirin also can be life-threatening
for patients with ischemic heart disease or cerebral
vascular disease. Ribavirin is teratogenic, and female
patients should avoid becoming pregnant during
therapy.
Other treatments, including
corticosteroids, ursodiol,
and thymosin, have not been effective. High iron levels
in the liver might reduce the efficacy of interferon. Use of iron reduction therapy (phlebotomy or
chelation)
in combination with interferon has been studied, but results have been inconclusive. Because patients are
becoming more interested in alternative therapies
(e.g., traditional Chinese medicine, antioxidants,
naturopathy, and homeopathy), physicians should
be prepared to address questions regarding these
topics.
Click here
for recommendations from the National
Institutes of Health (NIH) on the treatment of
chronic hepatitis C.

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