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Interferon Beta
Is Effective for Early Retreatment of Relapsers with Genotype 1b
and Low HCV Viral Load
Interferon (IFN)
retreatment for hepatitis C virus (HCV)
relapsers has been effective
under some conditions. In the current study, researchers
conducted a controlled trial of
IFN beta retreatment for
HCV relapsers after IFN alpha.
The
investigators gave IFN beta 6MIU therapy to 43 patients who had
relapse of HCV after the
24 weeks IFN alpha monotherapy.
The 43
patients were randomly assigned to two groups: Group A started
retreatment within 4 weeks after relapse; and Group B started
retreatment 24 weeks or more after relapse.
Results
Nine patients
showed sustained virological response (SR) to the retreatment.
All of these
patients were in a low viral load subgroup.
The SR rate in
Group A (8/22, 36%) was significantly higher than in Group B
(1/21, 5%) (P=0.0128).
Among patients
with lower viral load, the SR rate in Group A (8/10, 80%) was
also significantly higher than in Group B (1/8, 13%) (P=0.0076).
Conclusions
The authors
conclude, “IFN beta is effective for patients with
HCV low viral load, and
the sooner after the relapse the re-treatment is started, the
better the clinical results will be.”
Department of Internal Medicine, Shin-Kokura Hospital,
Kita-Kyushu, Japan.
03/23/05
Reference
H
Nomura and others. Efficacy of Early Retreatment with Interferon
Beta for Relapse in Patients with Genotype Ib Chronic Hepatitis
C.
Hepatology Research
28(1): 36-40. January 2005.
http://www.hivandhepatitis.com/hep_c/news/2005/032305_a.html |
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Interferon's Benefits for Fibrosis Studied
by John C.
Martin Article Date: 03-16-05
People with liver fibrosis can see an improvement in
their disease after taking
interferon-alfa, says a new study from
Greece, but those who achieve a
sustained virological response (SVR)
have the best outcomes.1
Still, even non-responders and those who relapse can
see a benefit from the medication, depending on the length of time that
they take it, according to doctors in the Academic Department of
Medicine at Hippokration Hospital of Athens, Greece.
Clarifying the Mystery
The researchers wanted to learn more about the specific effect that this
standard
hepatitis therapy has on their patients
with fibrosis of the liver. Currently, the only measure of interferon
treatment failure or success is a patient's ability to achieve an SVR,
or sustained virological response, defined as maintaining undetectable
levels of the virus for at least 6 months after therapy is discontinued.
Fibrosis is scarring of the liver that occurs in
hepatitis infection. It can potentially progress to
cirrhosis, a type of chronic liver
disease in which normal cells are damaged and replaced by scar tissue.
Cirrhosis ranks as the eighth leading cause of death in the United
States.2
"The possible effect of interferon-alfa on liver
fibrosis progression has not been adequately studied in chronic
hepatitis B,” wrote George Papatheodoridis, MD, and his colleagues.
Comparing Treated with Untreated
Patients
In an attempt to come up with more answers, Papatheodoridis'
group retrospectively evaluated 147 patients with chronic hepatitis B
who were also E antigen-negative. That's a mutant form of hepatitis B
that tends to be more resistant to treatment. "In fact, there were
suggestions that only
nucleoside analogues have a beneficial
effect on liver histology" in these patients, explained Papatheordoridis,
an associate professor in Medicine and Gastroenterology who led the
study, in an interview with Priority Healthcare. Nucleoside analogs like
Hepsera (adefovir dipivoxil) and Epivir-HBV (lamivudine) interfere with
the activity of an enzyme that the hepatitis B virus uses to make copies
of itself.3
One hundred twenty patients had previously been
treated with interferon alfa, and the remaining 27 had not. Each patient
had undergone at least 2 biopsies previously, as well.
Papatheodoridis and his colleagues found fibrosis
improved in about 17 percent of the treated patients, overall, compared
to just 4 percent of those who didn't receive
therapy. Those who achieved sustained
virological responses had the most improvement in liver fibrosis
compared to relapsers, who had the worst improvement.
Even Relapsers and Nonresponders
Benefited
They also learned that interferon induced a sustained response in
30 patients, but 57 only had an initial response, and then subsequently
relapsed. The remaining 33 had no response.
Fibrosis also worsened in about a third of those
treated—the worst progression mostly in nonresponders. But that compares
to some 70 percent of those who didn't undergo interferon therapy at
all, the researchers found.
"The annual rate of fibrosis progression was worse in
the untreated than in treated patients," Papatheodoridis and his
colleagues wrote, a significant finding, even considering nonresponders
and relapsers.
The research team also discovered that several key
factors increased the likelihood of fibrosis progression: older age, and
worse liver disease or lower fibrosis level at the beginning of this
study.
Interferon Benefits Found in All
Cases
After collecting their data, the researchers summarized that
"interferon alfa significantly reduces the rate of fibrosis progression,
but such an effect is mainly observed in patients with sustained
biochemical responses." In those who relapse after initial treatment
with interferon and in non-responders, the beneficial effect on fibrosis
depends on how long treatment is given, they said.
"Sustained off-therapy response should remain the
measure of interferon efficacy," Papatheodoridis told Priority
Healthcare. "However, we showed that, although sustained off-therapy
response is the optimal outcome and results in significant improvement
of fibrosis, the worsening of liver fibrosis is slower in patients
without such a response (relapsers or non-responders) compared with
untreated cases."
Though the benefit for non-responders and relapsers
may be temporary, other antiviral agents could be subsequently
prescribed, Papatheodoridis explained.
'First Therapeutic Option'
Intron-A is the form of interferon alfa
used to treat people with hepatitis B. But it's not necessarily intended
for every HBV patient. Those who are chronically infected, have higher
liver enzyme levels and actively replicating virus are typical
candidates for this therapy. Clinical studies have shown that
approximately 45 percent of patients prescribed Intron-A respond to the
therapy.4
"We will continue further studies in more detailed
aspects of this area," Papatheodoridis said. "I think that our study
further strengthens the suggestions that interferon should be the first
therapeutic option for patients with HBV E antigen-negative chronic
hepatitis B."
1. Papatheodoridis GV, Petraki K, Cholongitas E, Kanta
E, Ketikoglou I, Manesis EK. J Viral Hepat 2005
Mar;12(2):199-206.
2. American Liver Foundation. What Are the Diseases that Affect the
Liver? Available at: http://www.liverfoundation.org/cgi-bin/dbs/articles.cgi
db=articles&uid=default&ID=1043&view_records=1.
Accessed March 11, 2005.
3. Zoulim F, Trepo C. New antiviral agents for the therapy of chronic
hepatitis B virus infection. Intervirology 1999;42(2-3):125-44.
4. Hepatitis Neighborhood. HBV Medications: Intron-A, Epivir HBV &
Hepsera. Available at: http://www.hepatitisneighborhood.com/content/
treatment_options/medications_for_hepatitis_287.aspx.
Accessed March 11, 2005.
John Martin is a long-time health journalist and
an editor for Priority Healthcare. His credits include coverage of
health news for the website of Fox Television's The Health Network, and
articles for the New York Post and other consumer and trade
publications.
http://www.hepatitisneighborhood.com/content/in_the_news/archive_2283.aspx
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When Does Mother-to-Child Transmission of Hepatitis C
Virus Occur?
The rate of
HCV transmission from
mother to child is generally though to be very rare.
However, it does occur, however rarely. The aim of the present
prospective cohort study was to investigate when hepatitis C virus (HCV)
infection from mother to child occurs, and to evaluate possible
associated factors.
Fifty-four HCV
positive children and their mothers were tested within three days of
birth. The main outcome measure of the study was
HCV RNA polymerase chain reaction (PCR) results.
Results
Seventeen of the
children (31%) were positive in the first 3 days of life and could be
assumed to have acquired infection in utero.
Testing PCR positive
was not associated with sex (53% v 49% boys; p=0.77) or mode of delivery
(29% elective caesarean
section in both groups; p=0.98).
Children with evidence
of intrauterine infection were significantly more likely to be of lower
birth weight and infected with
genotype 1 (58% v 12%, p=0.01).
Although a higher
proportion of infants born to
HCV/HIV
co-infected women were
HCV PCR positive in the first 3 days
of life, this difference did not reach statistical significance.
Excluding infants born
to co-infected women did not affect the results.
Thirty seven of the children (68%) were
negative in the first 3 days of life, 27 of whom were positive when
tested again at 3 months, and nine were first PCR positive after 3
months (one child had no further tests).
Conclusions
The authors conclude,
“These results suggest that at least one third and up to a half of
infected children acquired infection in utero. Although postpartum
transmission cannot be excluded, these data suggest that it is rare. The
role of
HCV genotypes in the timing and mechanism of infection
should be explored further.”
Paediatric HIV
Service, Royal Hospital for Sick Children, Edinburgh, Scotland, UK.
03/16/05
References
J Mok and
others (for the European Paediatric Hepatitis C Virus Network). When
does mother to child transmission of hepatitis C virus occur?
Arch Dis
Child Fetal Neonatal Ed
90(2): F156-160. March
2005.
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Swedish study links HCV infection with hematologic
malignancies |
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By Noelle Holly, MD
March 8, 2005 —
Researchers in Sweden reported an increased incidence of 2
lymphoproliferative disorders, non-Hodgkin's lymphoma (NHL) and multiple
myeloma, among patients infected with hepatitis C virus (HCV) in a
large-scale retrospective study.
Hepatitis C is on the rise in many parts of the world, including
Sweden, with most viral transmission having occurred in the 1960s and
1970s. Many of the more than 170 million individuals worldwide infected
with HCV have mild or no symptoms but remain at risk for cirrhosis,
end-stage liver disease, and hepatocellular carcinoma. In addition to
the well known hepatotropic nature of HCV, recent concerns regarding a
lymphotropic effect have arisen.
HCV infection has been causally associated with essential mixed
cryoglobulinemia, and some studies have shown a link with B-cell NHL,
multiple myeloma, and thyroid cancer. Although the mechanism is unclear,
HCV antigens may stimulate B-cell proliferation. Further support for an
association between HCV and nonhepatic cancer lies in the finding that
anti-HCV treatment has been reported to concomitantly induce lymphoma
regression.
Duberg and colleagues investigated the possible role of HCV infection
in the development of NHL, multiple myeloma, acute lymphatic lymphoma
(ALL), thyroid cancer, chronic lymphocytic leukemia (CLL), and Hodgkin's
lymphoma (HL). Whereas past studies have evaluated the rate of HCV
infection among cancer patients, this study used the reverse approach by
examining the prevalence of these cancers among a large population of
HCV-infected patients.
Sweden's nationwide citizen registry allowed for the identification
of those with both HCV infection and cancer by linking the database of
the Swedish Institute for Infectious Disease Control with that of the
Swedish Cancer Registry. Among these, patients hospitalized for
HIV-related conditions or organ transplant were identified by ICD coding
within the Swedish Hospital Discharge Register. Dates of infection were
approximated based on demographic and epidemiologic factors and the
likely route of infection. Patients were stratified by the assumed time
of previous HCV infection: less than 15 years, or 15 years or longer. A
standard incidence ratio was calculated for each cancer diagnosis by
dividing the number of cases observed in the HCV population by the
expected number of cases in the general population.
Between 1990 (when HCV assays became available) and 2000, 27,150
patients in Sweden were notified of HCV infection, of whom 97 had 1 of 6
cancers. Two patients were excluded from analysis for having a diagnosis
of another malignancy prior to the estimated date of HCV infection, and
these were the only patients in the analysis with a history of organ
transplant. To reduce bias, 57 patients were excluded because their
malignancy was diagnosed either before or within 3 months of HCV
notification. (Due to the latent nature of HCV infection and the
potentially imprecise estimate of infection date, these patients most
likely became infected prior to developing cancer, meaning this study
probably underestimates the incidence of HCV-related cancer.) The
resulting 38 evaluable patients with nonhepatic cancer following HCV
infection included 20 with NHL (4 of whom were HIV positive), 7 with
multiple myeloma, 5 with thyroid cancer, 4 with CLL, 1 with ALL, and 1
with Hodgkin's lymphoma. The overall observation time was 122,272
patient-years, and the mean age at diagnosis was 44 years.
Among patients with NHL 15 or more years after infection, nearly
twice as many cases as expected were observed in the HCV-infected
population, with an incidence ratio of 1.89 (95% confidence interval
[CI], 1.10-3.03). Excluding HIV-infected NHL patients, rates were still
elevated, with an incidence ratio of 1.56 for those 15 years or more
since infection and 1.86 for fewer than 15 years.
Similarly, preceding HCV infection more than doubled the risk for
multiple myeloma, with an incidence ratio of 2.54 for those infected 15
or more years earlier (95% CI, 1.11-5.69). Statistical significance was
not reached for the other cancers due to low numbers.
These findings concur with studies performed in Japan, Italy, and the
US. Most patients in the present study were thought to have been
infected for at least 15 years prior to the development of nonhepatic
cancer, which corresponds with the indolent nature of this virus. While
immunodeficiency due to HIV infection is a known cause of lymphoma, the
role of coinfection with HCV cannot be ruled out. The authors encouraged
research on a "smaller but better-characterized cohort" to further
elucidate the implications of HCV infection in cancer.
Reference
Duberg AS, Nordstrom M, Torner A, et al. Non-Hodgkin's lymphoma and
other nonhepatic malignancies in Swedish patients with hepatitis C virus
infection. Hepatology. 2005;41:652-659.
http://clinicaloptions.com/hep/news/news_imed_360.asp |
Why is HCV So
Resilient?
by John C. Martin
Article Date: 03-02-05
One of the reasons it's so challenging to treat people with hepatitis C
successfully is due to the virus' resilience in the body. While our immune
systems are inherently designed to fight off foreign substances like
bacteria and viruses almost as soon as they enter the body, hepatitis C (HCV)
has a built-in evasive mechanism that helps protect it from an otherwise
devastating and irreparable blow. It's like a military submarine that sends
out decoys to throw off an impending torpedo. As a result, HCV is able to
successfully replicate, or make copies of itself.
Because of its seemingly omnipotent nature, HCV can persist in the body
for decades after an initial infection, sometimes causing so much damage to
a person's liver that their only option in the end is a liver transplant
operation.
Uncovering HCV's Resilience
So, why is the hepatitis C virus able to evade the immune system? Scientists
at two universities in Texas think they may have found the answer. In a
study published online in the journal The Proceedings of the National
Academy of Sciences,1 researchers explain how HCV is able to shut down two
key elements of the immune response through a protein the virus uses called
NS3/4A protease. Essentially, HCV is able to circumvent the immune response
by preventing the production of signaling molecules in the immune system,
which signal other immune cells to go after foreign invaders in the body.
In an additional paper,2 the same scientists described the process by
which the hepatitis virus blocks signaling molecules in the immune system
from calling up other immune system cells to launch an attack against HCV.
In the second study, the scientists showed that certain liver cells allow
HCV replication to occur due to an abnormal inactivation of an immune system
signaling molecule known as retinoic acid-inducible gene I (RIG-I).
Blocking HCV Replication Through Medicine
This research comes on the heels of preliminary results of clinical trials
testing the effectiveness of medications that target HCV's ability to
circumvent an immune attack. It's been suggested that these drugs called
protease inhibitors block hepatitis C's ability to make copies of itself
once it infects the liver particularly by blocking the virus' immune system
evasion.3,4
The medications work similarly to protease inhibitors for HIV. Those
drugs block the activity of a protein that the AIDS virus uses to make
copies of itself.5
"At least one protease inhibitor has had extraordinary activity against
hepatitis C in human clinical trials, but we're going to need to improve on
it in a number of ways, including reducing the potential for the virus to
become resistant to it," said Stanley Lemon, MD, a senior author on the
paper, and director of the Hepatitis C Research Center at the University of
Texas Medical Branch at Galveston.
"A better understanding of how NS3/4A does its work in blocking the
immune response will help make that possible," said Lemon, who is also
Professor and Dean of Medicine in the departments of Microbiology &
Immunology and Internal Medicine.
An 'Impressive' Drug in This Class
One experimental medication in this class has been named BILN 2061.6 The
medication, given to patients orally, has shown an "impressive" ability to
reduce levels of the hepatitis C virus, according to experts.
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FDA Approvals: Atacand, Pegasys
Plus Copegus, Triage APAP TOX Screen
Yael Waknine
March 3, 2005 — The U.S. Food and Drug Administration (FDA) has approved
candesartan cilexitil for use in chronic heart failure with left ventricular
dysfunction to reduce the risk of mortality and hospitalization due to
cardiovascular causes; peginterferon alfa-2a [40 KD] plus ribavirin therapy
for the treatment of hepatitis C infection in patients coinfected with the
HIV virus; and a urine screening test for acetaminophen.
Candesartan (Atacand) for Reduction of CV Mortality, Hospitalization
in CHF Patients
On Feb. 25, the FDA approved a new indication for candesartan cilexitil (Atacand,
marketed in the U.S. by AstraZeneca Pharmaceuticals, Inc.), allowing its use
in the treatment of chronic heart failure (CHF; New York Heart Association [NYHA]
class II-IV and ejection fraction [EF] of 40% or less) to reduce the risk of
death from cardiovascular causes and reduce heart failure–related
hospitalizations.
The selective angiotensin receptor blocker may be used as an alternative
drug for patients who have developed tolerance to angiotensin-converting
enzyme (ACE) inhibitor therapy, or it may be used in addition to ongoing
therapeutic regimens (with or without ACE inhibitors).
Approval of the CHF indication was primarily based on the results of the
Candesartan in Heart failure — Assessment of Reduction in Mortality and
morbidity (CHARM) trial, showing that the addition of candesartan to
standard heart failure therapy in ACE-intolerant patients significantly
reduced the risk of cardiovascular death (23% reduction; P < .001)
and heart failure hospitalizations (incidence, 334 vs 406 with placebo).
A second study demonstrated similar results in patients with NYHA class
II to IV heart failure and EF of 40% or less who were receiving submaximal
doses of ACE inhibitors. Combined study results showed that candesartan
reduced the risk of cardiovascular mortality by 15% (P = .005) and
significantly improved symptoms as assessed by NYHA functional class (P
< .001).
The recommended initial daily dose of candesartan for CHF is 4 mg, with a
target dose of 32 mg to be achieved by doubling the dose at two-week
intervals as tolerated.
Adverse events related to candesartan use include hypotension, abnormal
renal function, and hyperkalemia. Monitoring of blood pressure, serum
creatinine, and serum potassium is recommended during dose escalations and
at regular intervals.
Candesartan was approved by the FDA in July 1998 for use alone or in
combination with other antihypertensive agents in the treatment of
hypertension. The CHF indication for candesartan was approved by all member
states of the European Union (with the exception of France) in November
2004.
Peginterferon alfa-2a (Pegasys) Plus Ribavirin (Copegus) for HCV in
Patients Coinfected With HIV
On Feb. 25, the FDA approved an expanded indication for combination
therapy with peginterferon alfa-2a [40 KD] and ribavirin (Pegasys and
Copegus, both made by Hoffman La-Roche, Inc.), allowing use of the
combination in the treatment of chronic hepatitis C virus (HCV) in patients
coinfected with HIV.
An indication previously approved in October 2002 allowed use of the
combination (or interferon therapy alone) to treat HCV in adults with
compensated liver disease and no prior history of interferon therapy.
According to a company news release, it is estimated that 30% of
HIV-infected patients in the U.S. are coinfected with HCV. HCV is more
resistant to treatment and progresses more quickly to liver failure in
patients with HIV.
The approval was based on the results of the AIDS Pegasys Ribavirin
International Co-infection Trial (APRICOT), which compared the effects of
therapy with peginterferon alfa-2a plus ribavirin, peginterferon alfa-2a
monotherapy, and traditional interferon alfa-2a plus ribavirin in 860
patients coinfected with HCV and HIV.
Results at 48 weeks showed that a significantly greater percentage of
patients treated with peginterferon/ribavirin achieved a sustained virologic
response compared with peginterferon monotherapy or conventional interferon/ribavirin
(40% vs 20% and 10%, respectively).
Therapy with peginterferon/ribavirin was significantly more effective in
eliciting a sustained virologic response in patients with genotype 1 (29% vs
7%) and genotypes 2/3 (62% vs 20%) compared with conventional interferon/ribavirin
treatment. In patients who did not achieve a sustained virologic response,
peginterferon/ribavirin therapy was associated with the greatest overall
histological improvement.
Adverse events related to use of the drug combination were similar to
those observed in monoinfected patients and included neutropenia, anemia,
thrombocytopenia, weight loss, and mood alteration.
Peginterferon alfa-2a is dosed as a once-weekly 180-µg subcutaneous
injection. Ribavirin is available in 200-mg tablets and administered in
split doses totaling 800 to 1200 mg daily.
The expanded indication was approved for use in the European Union on
Feb. 3, 2005.
Point-of-Care Urine Test (Triage TOX) Detects Acetaminophen 30 Minutes
After Ingestion
On March 2, the FDA approved a screening test (Triage TOX Drug Screen
with Acetaminophen, made by Biosite Inc.) for use with the company's Triage
MeterPlus device in the qualitative detection of acetaminophen in urine.
Toxicity can occur after intentional or accidental ingestion of
approximately 150 to 200 mg/kg acetaminophen, and symptoms such as nausea,
vomiting, and abdominal pain may be subtle or delayed by over 24 hours.
Liver damage and death may occur if the antidote N-acetylcysteine is not
administered within eight hours of overdosage.
The test is capable of detecting the presence of acetaminophen as soon as
30 minutes after ingestion of a therapeutic dose of extra-strength
acetaminophen tablets in adults, and it provides results in 15 minutes.
Reviewed by Gary D. Vogin, MD
FDA Approvals: Atacand, Pegasys Plus Copegus, Triage
APAP TOX Screen
Texas scientists discover how hepatitis C
short-circuits the immune system
GALVESTON, Texas—To find an effective treatment for hepatitis C, which
chronically infects nearly 200 million people worldwide, researchers need to
understand how the virus is able to avoid destruction by the immune system.
Hepatitis C persists in the body for decades after an initial infection,
often causing so much liver damage that liver transplantation may be a
patient’s only chance for survival.
Now, scientists at the University of Texas Medical Branch at Galveston (UTMB)
and the University of Texas Southwestern Medical Center in Dallas have
figured out two key parts of hepatitis C’s strategy for evading the human
immune response. In papers to be published online today in the Proceedings
of the National Academy of Sciences (PNAS), UTMB and UT-Southwestern
researchers define two critical elements of the immune response shut down by
a hepatitis C virus protein called NS3/4A. These virus-caused “short
circuits” prevent the production of signaling molecules that mobilize cells’
antiviral defenses.
In an additional paper, appearing in the current Journal of Virology and
available now online, the UT Southwestern and UTMB researchers demonstrate
the critical role played by one of the “circuits,” known as the RIG-I
pathway, in cellular defense against hepatitis C virus.
The discoveries are particularly important in light of recent promising
results from early clinical trials of new investigational drugs that target
NS3/4A and both block the reproduction of hepatitis C and nullify its
ability to dodge immune defenses, according to Stanley M. Lemon, a senior
author on the papers and director of UTMB’s National Institutes of
Health-funded hepatitis C research center. “At least one protease inhibitor
has had extraordinary activity against hepatitis C in human clinical trials,
but we’re going to need to improve on it in a number of ways, including
reducing the potential for the virus to become resistant to it,” Lemon said.
“A better understanding of how NS3/4A does its work in blocking the immune
response will help make that possible.”
Lemon’s group, including lead author and assistant professor of
microbiology and immunology Kui Li, postdoctoral fellows Josephine C.
Ferreon, Mitsuyasu Nakamura, Allan C.M. Ferreon and Masanori Ikeda,
collaborated with Michael Gale and Eileen Foy of UT Southwestern on one PNAS
paper, “Immune evasion by hepatitis C virus NS3/4A protease-mediated
cleavage of the Toll-like receptor 3 adaptor protein TRIF.” Lemon and Li
also collaborated with the UT-Southwestern team led by Gale on the second
PNAS paper (“Control of antiviral defenses through hepatitis C virus
disruption of retinoic acid-inducible gene-I signaling”), on which Foy is
the lead author, and Rhea Sumpter, Jr., Yueh-Ming Loo, Cynthia L. Johnson,
Chunfu Wang, and Penny Mar-Fish are co-authors.
The PNAS articles can be found on the journal’s Early Edition web page,
located at
http://www.pnas.org/papbyrecent.shtml. The
Journal of Virology paper is at
http://jvi.asm.org/cgi/content/full/79/5/2689.
Texas scientists
discover how hepatitis C short-circuits the immune system
Ribavirin Plays Critical Role in the Response to
Peginterferon-based Anti-HCV Therapy
By Marina Nunez, MD, PhD
The coadjuvant effect of
ribavirin (RBV) seems to be crucial to achieve response to IFN-based anti-HCV
therapy. French investigators examined the relationship between RBV plasma
concentrations and sustained virological response (SVR) in 30 HIV/HCV-coinfected
patients treated for 48 weeks with
pegIFN alfa-2a (Pegasys)+RBV therapy [1].
The mean minimum
concentration at steady state was 1.8 microgram/mL. In multivariate
analysis, SVR was predicted both by
HCV
genotype and by minimum RBV plasma levels at steady state.
Moreover, 1 microgram/mL was identified as the threshold predicting SVR.
The role of adequate RBV
plasma levels early during the course of anti-HCV treatment was investigated
by Spanish investigators [2]. They examined 98 patients, measuring
RBV plasma concentrations at weeks 4 and 12 of treatment with pegIFN-alfa2a
(Pegasys)+RBV.
Their mean RBV levels were
2.71 microgram/mL and 2.72 microgram/mL at weeks 4 and 12, respectively.
Early
virological response, defined as > 2 log drop in HCV RNA levels
positively correlated with RBV plasma levels at weeks 4 and 12.
The investigators also
found that having RBV concentrations above 2.7 microgram/mL predicted early
virological response [OR 2.3 (95%CI 1.0-5.2); p=0.04].
Conclusions
The results of both
studies underline the important role of RBV for the achievement of response,
and suggest that early RBV monitoring might be useful in the management of
HIV/HCV-coinfected subjects receiving anti-HCV treatment to optimize
RBV
doses.
In addition, the second
study gives new insight in the action of RBV, which seems not only reduce
relapses after initial response, but also enhance early response to
treatment.
02/28/05
References
1. D Breilh and others.
Plasma target concentration of ribavirin in HCV/HIV-co-infected patients.
Abstract 928. 12th Conference on Retroviruses and Opportunistic Infections.
February 22-25, 2005. Boston, MA.
2. A Rendón and others.
Ribavirin plasma concentrations predict early virological response as well
as anemia in anti-hepatitis therapy. Abstract 929. 12th Conference on
Retroviruses and Opportunistic Infections. February 22-25, 2005. Boston, MA.
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