Hepatitis
C
Clinical Trials
Hepatitis C is recognized as a global health problem, with an
estimated worldwide prevalence of more than 170 million and
no foreseeable vaccine. As in hepatitis B, Zadaxin is safe and
effective for the treatment of chronic hepatitis C when used
in combination with IFNá. Although the hepatitis B and
C viruses are not structurally related, they are similar in
that they are both associated with a high incidence of liver
disease, including cirrhosis and hepatocellular carcinoma. They
both induce hepatocellular damage, whether through direct cytotoxicity
or through induction of immune mechanisms that lead to hepatocellular
necrosis. Clearance of viral infection in both viral diseases
requires immune involvement, although the exact mechanism for
clearance may be different. A much higher percentage of patients
(ca, 85%) infected with the hepatitis C virus go on to chronic
infection.
Current management of hepatitis C is centered on the use of
interferons. Unfortunately response occurs in a minority of
patients and sustained response in fewer. IFNα-2b
and ribavirin, a new combination, has been approved to treat
chronic hepatitis C in naïve patients and in patients who
have relapsed following standard interferon treatment. The new
combination shows fewer relapses than interferon alone but with
additional side effects. In addition to the typical side effects
from interferon, ribavirin causes anemia in up to 25% of patients,104
which can be serious especially in patients with underlying
cardiovascular disease. Depression, suicidal intention, and
suicides have occurred in patients treated with the combination
of ribavirin and IFNα.
More recently, PEG-IFNα,
a covalent conjugate of recombinant IFNα
with a PEG polyethylene glycol (PEG) moiety, has been approved
as monotherapy and in combination with ribavirin for the treatment
of naïve patients with chronic hepatitis C. Pegylation
involves the attachment of polyethylene glycol to the interferon
molecule. Pegylation results in slower clearance of the interferon
molecule, allowing it to remain in the bloodstream longer, thereby
providing a more convenient, once-weekly dosing schedule for
patients and maintaining its ability to consistently suppress
the hepatitis C virus over the 1-week dosing period. In vitro
and in vivo studies suggest that the biological activity of
PEG-IFNα is derived
from its interferon alfa moiety. Despite the recent improvements,
the sustained response rate remains around 50%. The dissatisfaction
with the treatment response rate and the sustained response
rate has led to studies of interferon combined with other modalities,
such as Zadaxin. |
