The Swedish Study
Group has investigated the effectiveness and safety of the treatment
of patients with chronic hepatitis virus (HCV) infection with interferon
alfa-2b (Inrtron-A) and the antiviral agent ribavirin (Virazole) compared
to interferon alfa-2b alone. One hundred patients were randomized
in a double-blind fashion t receive treatment with interferon alfa-2b (3
MU, three times a week) in combination with ribavirin (1000-1200 mg per
day), or placebo for 24 weeks. Patients were followed for an additional
24 weeks to confirm a sustained virological response. The combination
of interferon alfa-2b and ribavirin was associated with a greater percentage
of patients achieving a sustained virological response than that observed
with interferon therapy alone (36% vs 18%; p=0.047). The authors
showed that chronic hepatitis C patients with high HCV RNA loads (>3 million
eq/ml) were the subgroup that benefited from concomitant interferon alfa-2b
and ribavirin therapy. (Reichard O, et al Lancet 1998; 351:
83-87)
EFFECT OF INITIAL INTERFERON
DOSING AND DOSE ON EARLY RESPONSE TO COMBINATION THERAPY WITH RIBAVIRIN
IN CHRONIC HEPATITIS C. Ferenci P., Steindl P., Datz Ch., Lin
W. Vogel W. on behalf of the Austrian Hepatitis Study Group, Vienna and
Innsbruck, Austria.
Patients with chronic
hepatitis C who become HCV RNA negative within the first weeks of antiviral
therapy are likely to become long-term responders. Recent data suggest
that the initial dose and dosing regime of interferon alpha (IFN) has an
impact on response rates. No information is available on the role
of IFN induction therapy in combination with ribavirin. Therefore
the efficacy of various initial IFN dosing regimens in combination with
ribavirin on response rates was studied after two weeks of therapy.
Study Protocol: Data of the first 36 patients with chronic hepatitis
C participating in a prospective randomized controlled trial of IFN/ribavirin
combination therapy were evaluated. All patiens received ribavirin
(1 to 1.2 g/d) and IFN-alpha2b(IntronA, Schering-Plough). (Group
A: 10 MU/d; Group B: 5 MU/d; Group C: 5 MU every other
day). Prior to treatment, all had an AT >1.5 ULN and were anti HCV
and HCV RNA (PCR) positive. Complete response was defined by
disappearance of serum HCV RNA. HCV RNA was determined prior to and
after 2 weeks of treatment. Pretreatment characteristics of the randomized
patiens were: group A: n=15; m/f: 12/3; age: 41.6 yrs
(range: 29-63); group B: ;n=10; m/f: 5/5; age: 47.4 (23-61);
group C: n-11; m/f: 9/2; age: 46.3 (35-56). Results:
Group
(IFN dose)
neg. N (%)
pos. N
|
A (10 MU/d) |
9 (60 |
6 |
|
B (5 MU/d) |
4 (40) |
6 |
|
C (5 MU/2d) |
1 (9) |
10 |
|
TOTAL |
14 (39) |
22 |
These data indicate
that the initial daily dosing of IFN rather than the IFN dose itself is
an important predictor of early response to IFN-ribavirin combination therapy
in chronic hepatitis C.
DAILY HIGH-DOSE INTERFERON SUPPRESSES IN VIREMIA
IN PATIENTS WITH CHRONIC HEPATITIS C WITHOUT A PREVIOUS SUSTAINED RESPONSE
TO STANDARD TREATMENT. JB Gross, DJ Brandhagen, JJ Poterucha, AA
Gossard, DD Douglas, and the Midwest Hepatitis Study Group, Mayo Clinic,
Rochester, MN 55905.
The majority of patients with chronic
hepatitis C do not have a sustained response to interferon (IFN) at a dose
equivalent to IFN-alpha2b, 3 MU 3x/week (TIW). Combination therapy
with rebavirin was recently shown to be superior to interferon alone for
retreatment of relapsers, but half of patieint were still unable to achieve
a sustained response. Recent acute-dose studies in previoulsly untreated
patients suggest that daily IFN dosing may suppress viremia better than
TIW dosing. AIM: to compare the effects of daily vs.
TIW dosing on serum ALT and HCV RNA levels in patients without a previous
sustained response to interferon. Methods: Randomized treatment
trial, stratified for genotype 1, RNA level > 2 MEq, histologic cirrhosis,
and nonresponder (NR) vs. relapser (RE). Patients had chronic hepatitis
biochemically and histologically, positive serum HCV RNA, and had previously
been treated for at least 12 wks. with IFN-alpha2b, 3 MU TIW (or equivalent).
Patients were randomized to IFN-alpha2b, 5 MU daily or 5 MU TIW for 4 wks.
Results: Forty-five patients have completed 4 wks of treatment.
Median baseline ALT wa 93 U/L in NR-TIW and 115 in NR-Daily, and
106 in RE-TIW and 81 in RE-Daily. ALT normalized in 15% of NR-TIW
vs 30% of NR-Daily, and 35% of RE-TIW vs. 75% of RE-Daily. RNA data
are presented in the table (rounded to nearest 5%):
|
Median Serum |
RNA (MEq) |
Frequenc |
y of.... |
| Non-Responders |
Baseline
|
4 Weeks
|
Decr. > 2logs
|
Negative
|
| TIW (n=13) |
3.7
|
0.76
|
15%
|
0
|
| Daily (n=14) |
3.9
|
0.80
|
30%
|
25%
|
| Relapsers |
|
|
|
|
| TIW (n=9) |
3.7
|
0.20
|
45%
|
10%
|
| Daily (n=9) |
2.6
|
0.0001
|
85%
|
45%
|
Conclusion: Daily administration
of high-dose interferon appears to be more effective than TIW dosing in
suppressing and readication viremia after 4 weeks in patients without a
sustained response to standard interferon therapy. This observation
may be of value in designing longterm suppression regimens.
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