Prev: Well, what about interferon?
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From: amzolt on 8 Mar 2007 23:58
>From the site:
http://www.hepatitiscfree.com/interferon.html

AMERICAN LIVER FOUNDATION
Information 2002:
The Liver in Health and Disease


HEPATITIS C: THERAPY
Gary L. Davis, MD
University of Florida
Gainesville, Florida


Key Points:

1. Chronic hepatitis C is a heterogeneous disease whose natural
history and response to treatment is probably influenced by multiple
factors including but not limited to viral genotype, level of viral
replication, and histology.

2. Interferon is the only agent of proven efficacy in the treatment
of hepatitis C. Standard treatment is interferon alfa-2b at a dose of
three million units three times a week. The initial course of
treatment is 6 months, but nearly all patients relapse and require
retreatment. The goal of interferon treatment is suppression of
active disease; this usually requires long term therapy. Eradication
of virus does not appear to be a realistic goal in most patients

3. Higher doses and longer duration of initial therapy have limited
benefit over standard therapy. However, higher initial doses may
increase the interval before relapse and escalation of the dose may
achieve response in some non-responders.

4. Treatment trials have tended to study relatively homogenous
patient groups and the possibility of extrapolating these results to
different patient populations is extremely limited. This is
especially true of studies from geographic areas. Thus, future
studies should: (1) consider genotype, viral load, and histology in
stratification; and (2) include a control group of standard treatment
for comparison.

5. Selection of patients for this chronic treatment remains
controversial. Treatment of patients with active disease is most
cost- effective, but other factors such as the degree of symptoms
must be considered.

6. The definition of response to treatment is evolving as a
technology of measurement of HCV improves. It is likely that future
treatment strategies will be dependent upon virologic endpoints in
addition to, or instead of, serum ALT.

7. Different agents and adjuncts have been incompletely studied to
date. Ribavirin reduces serum ALT levels to normal and improves
fatigue in nearly half of patients. Histology and virus levels do not
appear to be significantly altered. The mechanism of its action of
this interesting agent is not clear.


INTRODUCTION

The first trial of interferon as therapy for chronic non-A, non-B
hepatitis was reported in 1986. This pilot study demonstrated that
alpha interferon therapy:
(1) was effective at low doses (in comparison to doses previously
shown to be required for hepatitis B and D); (2) decreased serum ALT
levels promptly upon initiation of therapy, a pattern suggestive of
an antiviral effect of interferon; and (3) was usually associated
with relapse when treatment was stopped, indicating a failure to
eradicate the virus. Many subsequent controlled studies have now
confirmed all of these original observations. A dose of 3 million
units of recombinant interferon alfa-2b thrice weekly for 6 months is
the currently approved standard for initial therapy in the United
States. With the discovery of the hepatitis C virus responsible for
non-A, non-B hepatitis and the availability of moderately sensitive
techniques for detaching the virus, it is now apparent that the
biochemical response to interferon (normalization of ALT) is
associated with loss of detectable viremia; thus, the primary
response it interferon is indeed due to the antiviral effects of the
drug. However, the high relapse rate confirms the earlier suspicion
that interferon is usually unable to eradicate the virus, which
persists at levels below the current limits of detection in serum,
liver, or peripheral blood mononuclear cells.

It is apparent that the usual effect of interferon in patients with
chronic hepatitis C who respond to this therapy is one of viral
suppression, not eradication or cure. Sustained or prolonged response
to treatment (persistently normal ALT levels) occurs in only 15-20%
of patients and is often associated with detectable viremia despite
the biochemical absence of apparent hepatic injury. The observations
from these early studies are important and must be considered in
establishing appropriate justification and goals for interferon
therapy in clinical practice. Several crucial points must be made:

1. Interferon therapy appears to eradicate or cure infection in
only a small proportion of patients. Thus, cure is an unrealistic
goal of current interferon regimens.
2. Interferon is suppressive to the hepatitis C virus. The goal of
therapy should be to suppress infection to a degree that liver
disease is minimized.
3. The currently approved regimen of therapy (3 million units 3x
per week for 6 months) is suboptimal. It should be considered as
initial therapy, not as definitive therapy. The goal of chronic viral
suppression will require prolonged therapy, retreatment of relapse,
or maintenance regimens


Currently, clinical and basic research in hepatitis C is just
beginning to shed light on the issues important to therapeutics in
this confusing disease. It is now apparent that the disease course is
only slowly progressive in most patients; thus, histology may be
important in assessing the timing of therapeutic investigation. It is
evident that the natural history is different between genotypes. The
initial and long-term response to therapy is also effected by both
genotype and the level of viremia.

The differences in response to interferon therapy which occur as a
result of viral differences are critical to clinical research in
therapeutics. Literally dozens of studies of various interferon dose
regimens have appeared to demonstrate superiority of every
conceivable permutation of dosing to the currently accepted regimens.
However, few have compared these novel and potentially useful
regimens to standard dosing. Since genotypes are geographically
diverse and have significant influence on response to interferon,
trials conducted on one continent or even in different countries of
regions within a continent are not comparable. Changes in therapeutic
regimens from the current standard must be based on careful
comparisons of different regimens among genotypically similar
patients with similar viral loads. It is likely that a single dosing
strategy is not appropriate for all patients. Differences in the
hepatitis C virus from country to country may warrant local
modifications in interferon dosing. Unfortunately, this implies that
the considerable effort and expense of clinical trials may have
little applicability outside of the area where they are conducted. At
a bare minimum, genotype and the degree of viremia need to be
considered as stratification levels in designing future clinical
trials.


These statements are not intended to promote, sell, advertise
or otherwise induce anyone to purchase any product on this web site.

These statements have NOT been evaluated by the FDA
and are for informational purposes only.


All images ©2001 Lloyd Wright
Website maintained by FluxRostrum

From: greyhackles on 9 Mar 2007 09:57
On 8 Mar 2007 20:58:40 -0800, "amzolt" <amzolt(a)gmail.com> wrote:
[snipped]

What about it? The article is clearly out of date, to say the least...
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