THE CONSULTANT'S CHOICE
The optimal choice here is C.
Interferon alone produces
sustained response rates of just 10% to 20%20,21
therefore, is indicated as monotherapy only in patients
with contraindications to ribavirin(Drug information on ribavirin)
The duration—and efficacy—of combination therapy
are determined by a patient’s HCV genotype, of which
there are at least 6 distinct types. Genotypes 1, 2, and 3
are found most often in the United States; genotype 1 is
the most common. Genotype 4 is largely confined to the
Middle East and northern Africa, genotype 5 to South
Africa, and genotype 6 to Asia.22
Genotype is the most important predictor of response
to therapy. Patients infected with genotype 1 have a sustained
response rate (persistently normal aminotransferase
concentrations and absence of viral RNA at the end of
therapy and for at least 6 months thereafter) approximately
half that of patients infected with other genotypes.
Genotype also affects the length of therapy. Patients
infected with genotype 2 or 3 can be treated successfully
with 24 weeks of therapy. In those with genotype 1 infection,
the percentage who demonstrate sustained response
can be doubled by extending the duration of therapy
from 24 to 48 weeks. A 48-week course of therapy is therefore
recommended for our patient, who is infected with
Some studies have shown that patients with higher
pretreatment viral loads may respond better to longer
treatment regimens. However, because viral load fluctuates
over time and because assays of viral load are not
standardized, this variable is not currently used to determine
length of therapy.8
DRUGS AND DOSAGES
Combination therapy with interferon and ribavirin remains
the standard of care for patients with HCV infection.
Ribavirin, an oral nucleoside analogue, is active
against RNA and DNA viruses. Although it has little effect
as monotherapy, it augments the efficacy of interferon.
Pegylated interferon, which is created by attaching
a molecule of polyethylene glycol to interferon, results
in better bioavailability, a longer half-life, and better response
rates than conventional interferon. Pegylated interferon
was approved by the FDA as monotherapy for
hepatitis C in January 2001 and as combination therapy
with ribavirin in August 2001. Sustained virologic and
histologic response to pegylated interferon monotherapy
is superior to that seen with standard interferon and
similar to that seen with standard interferon/ribavirin
However, since ribavirin also augments the effect of
pegylated interferon, combination therapy with these 2
agents is the treatment of choice unless contraindicated.
The average sustained response rate for conventional interferon/
ribavirin is 40%; for pegylated interferon/ribavirin,
60%. Patients infected with genotypes 2 and 3 have
a sustained response rate with pegylated interferon/ribavirin
as high as 88%; those infected with genotype 1 have
a response rate of 48%.26-28
Our patient can expect a sustained
response rate of 30% to 50%, depending on the
type of interferon used.
The standard dosing regimen for conventional interferon
is 3 million units subcutaneously 3 times per week;
for pegylated interferon, 1.5 µg/kg subcutaneously once
weekly. Ribavirin is taken orally; 1200 mg/d for patients
who weigh at least 75 kg, and 1000 mg/d for those who
weigh less than 75 kg.
Our patient has begun therapy with conventional
interferon (pegylated interferon was not available) and
WHAT WOULD YOU DO NOW?
Check CBC count, LFTs, and TSH regularly.
Screen for depression regularly; also check
CBC count, LFTs, TSH, and viral load on a
After 24 weeks, screen for depression and
check CBC count, LFTs, TSH, and viral load.
Screen for depression regularly; check
CBC count, LFTs, and TSH on a regular basis;
check viral load after 24 weeks.