| |
"Effects of ribavirin combined with interferon-alpha2b
on viral kinetics during first 12 weeks of treatment in patients with
hepatitis C virus genotype 1 and high baseline viral loads"
Journal of Viral Hepatitis
Volume 11 Issue 5, September 2004
M. Enomoto1, S. Nishiguchi1, M. Kohmoto1, A. Tamori1, D. Habu1, T.
Takeda1, S. Seki1 and S. Shiomi2
1Department of Hepatology, Graduate School of Medicine, Osaka City
University Medical School, Osaka; and 2Department of Nuclear Medicine,
Graduate School of Medicine, Osaka City University Medical School,
Osaka, Japan
Summary
This study aimed to find how ribavirin increases viral disappearance
in patients with hepatitis C virus (HCV) of genotype 1 and high
baseline viral loads (>5.0 x105 copies/mL) when given with interferon
(IFN).
Using the real-time quantitative polymerase chain reaction, we
measured serum HCV in 20 patients during the first 12 weeks of therapy
with IFN-alpha2b and ribavirin. Controls were 10 similar patients
given IFN-alpha2b alone. IFN-alpha2b was given at 6 MU daily for 2
weeks, and then three times weekly. Ribavirin was given at 600 or 800
mg daily.
Serum HCV RNA decreased rapidly in the first phase, during the first
24 h of therapy (day 0), and more slowly in the early second phase
(days 1-14). The median decrease was by 1.41 and 0.078 log 10/day in
these two phases in the combination therapy group, and 0.90 and 0.081
log 10/day in the monotherapy group.
The difference between groups in the first phase was not significant
(P = 0.24), nor was that in the next phase (P = 0.68). Later in the
second phase, between days 14 and 84, the median decrease was larger
in the combination therapy group (0.030 log 10/day) than in the
monotherapy group (0.015 log 10/day, P = 0.035).
In patients with HCV genotype 1 and high viral loads, the effects of
ribavirin with IFN-alpha appeared slowly, after the earliest days of
treatment. A long-term favourable outcome of combination therapy may
be associated with a rapid viral decline in this later phase of
therapy.
ALSO:
Effects of
Ribavirin Combined with Interferon Alfa-2b on Viral Kinetics During First
12 Weeks of Treatment in Patients with HCV Genotype 1 and High Baseline
Viral Loads
This study aimed to find how ribavirin increases
viral eradication
in patients with hepatitis C virus (HCV)
genotype 1
and high baseline viral loads (>5.0 x105 copies/mL)
when given with
interferon (IFN).
Using the
real-time
quantitative polymerase chain reaction,
we measured serum HCV in 20 patients during the first 12 weeks of therapy
with
IFN- 2b
(Intron A) and ribavirin.
Controls were 10 similar patients given IFN-2b
alone.
IFN-2b
was given at 6 MU daily for 2 weeks, and then three times weekly.
Ribavirin was given at 600 or 800 mg daily.
Serum HCV RNA
decreased rapidly in the first phase, during the first 24 h of therapy
(day 0), and more slowly in the early second phase (days 1-14). The median
decrease was by 1.41 and 0.078 log 10/day in these two phases in the
combination therapy group, and 0.90 and 0.081 log 10/day in the
monotherapy group.
The
difference between groups in the first phase was not significant (P = 0.24),
nor was that in the next phase (P = 0.68).
Later in
the second phase, between days 14 and 84, the median decrease was larger
in the combination therapy group (0.030 log 10/day) than in the
monotherapy group (0.015 log 10/day, P = 0.035).
Conclusion
In
patients with HCV genotype 1 and high viral loads, the effects of
ribavirin with IFN-
appeared slowly, after the earliest days of treatment. A long-term
favorable outcome of combination therapy may be associated with a rapid
viral decline in this later phase of therapy.
FDA-approved Therapies for Hepatitis C
Ribavirin
HCV genotypes
09/20/04
Reference
M Enomoto and others.
Effects of ribavirin combined with interferon-
2b
on viral kinetics during first 12 weeks of treatment in patients with
hepatitis C virus genotype 1 and high baseline viral loads.
Journal of Viral Hepatitis
11(5): 448-455. September 2004.
http://www.hivandhepatitis.com/hep_c/news/2004/092004_b.html
Treatment with
Interferon Alfa and Ribavirin Among Hemodialysis patients
with Genotypes 1 and 4 Hepatitis C
Hepatitis C Viral (HCV) infection is the leading cause of chronic liver
disease in end-stage renal (kidney) disease patients (ESRD). The impact
of
HCV on patient and graft survival post transplantation is controversial.
The
most successful approach is to eliminate the virus while the patient is
on
dialysis prior to transplantation.
The main aim of this pilot study was to assess the efficacy of combined
alpha-interferon (alpha-IFN) and ribavirin treatment of HCV hemodialysis
(HDx) patients, by comparing the sustained virological response (SVR) to
that obtained by local historical data on treatment with alpha-IFN
alone.
A secondary aim was to establish the optimal therapeutic dose of
ribavirin
in this regimen.
Twenty HCV-HDx patients who were histologically (liver biopsy) and
virologically (HCV-PCR)-positive were selected randomly. They received
combination therapy with 3 million units (MU) of alpha-IFN and 200 mg of
ribavirin three times a week.
Initially nine patients were treated for 24 weeks. Later, another 11
patients were randomly selected to give the combination for 48 weeks.
Results
Six of the nine patients who were treated for 24 weeks (66%) became
HCV-PCR-negative by the end of the treatment period. They continued to
have
a sustained virologic response at 6 months after the cessation of
therapy.
Six of the 11 patients (55%) who were treated for 48 weeks became
HCV-PCR-negative at the end, and at 6 months after cessation of
treatment.
Of the first six responders, 4 (66%) maintained a sustained virologic
response at 1 year post cessation of therapy.
Nine of the 11 patients had genotype 4 and 1.
No side effects were reported for a ribavirin dose of 200 mg three times
a
week.
Conclusion
This pilot study suggests that combination treatment for 24 weeks and 48
weeks with 3 MU alpha-IFN and 200 mg ribavirin three times a week,
elicited
a sustained virologic response in HDx patients with HCV infection better
than IFN alone with minimal side effects.
A prospective, double-blind, controlled study using pegylated INF plus
ribavirin is currently underway.
Department of Nephrology, Riyadh Armed Forces Hospital, Riyadh, Kingdom
of
Saudi Arabia.
09/15/04
Reference
D H Mousa and others. Alpha-interferon with ribavirin in the treatment
of
hemodialysis patients with hepatitis C. Transplant Proceedings 36(6):
1831-1834. July-August 2004.
|
Can You Have Multiple Genotypes?
|
|
"Changes in the Prevalence of Hepatitis
C Virus Genotype among Injection Drug Users: A Highly Dynamic
Process"
The Journal of Infectious Diseases 2004;190:1199-1200
Matthias Schröter, Bernhard Zöllner, Rainer Laufs, and Heinz-Hubert
Feucht
Zentrum für Klinisch-Theoretische Medizin I, Institut für
Infektionsmedizin, Universitätsklinikum Hamburg Eppendorf, Hamburg,
Germany
To the Editor—With great interest we have read the article by van
Asten et al. in The Journal of Infectious Diseases [1]. An important
aspect of their study is its detailing of the introduction and
spread of "new" hepatitis C virus (HCV) genotypes among injection
drug users (IDUs).
Changes of subtype distributions in a given population were shown,
for the first time, by our group several years ago [2]. In that
study, it was demonstrated that subtype 1b was the prevailing
subtype in the German population until subtype 1a started spreading
in the early 1980s [2]. This led to a substantial change of the most
prevalent HCV subtype, especially in younger people. To highlight
the question of whether this change was a single effect, a
multicenter study was performed 2 years ago [3]. In that study, we
demonstrated that the epidemiology of HCV genotypes in IDUs is
subjected to highly dynamic changes. Profound changes in the
prevalence of different HCV genotypes were noted between 1994--1995
and 2000--2001, when large populations of IDUs (n = 144 and n = 172,
respectively) were compared. These changes are summarized in figure
1. The introduction of genotypes that were formerly unknown in this
risk population (4 and 2a/b) and the ability of these genotypes to
establish significant prevalence within a period of only 6 years are
remarkable.
The theory of 2 independently developing HCV epidemics had been
proposed elsewhere [4], because the epidemiology of HCV subtype 3a
and other subtypes seemed to be very different between IDUs and non-IDUs.
However, there are indications that the dynamics observed among IDUs
also influence the genotypic distribution among the entire
population of patients. Although subtype 3a was detected nearly
exclusively among IDUs in 1994--1995, 〜45% of patients infected with
subtype 3a had never been IDUs. In the majority of these people,
high-risk sexual behavior (HRSB) was the most probable risk factor
for acquiring HCV infection [3]. It can be assumed from these data
that the higher the prevalence of a certain genotype among the
population of IDUs, the higher is the risk of this genotype
spreading beyond the boundaries of the IDU scene. This is most
probably due to HRSB, which, today, is one of the major risk factors
for acquiring HCV [3, 5]. On the other hand, new genotypes can be
introduced in the population of IDUs. This has been demonstrated
very convincingly for genotype 4, which was introduced by immigrants
from northern Africa and the Arabian peninsula [1, 3], and for
genotype 2 [3]. In our population of patients, these genotypes
established a prevalence of 7% and 8%, respectively, within only 6
years (figure 1). In analogy to the findings for subtype 3a, these
genotypes may also spread over the boundaries of the IDU scene with
increasing prevalence.
However, knowledge of these dynamic changes of the distribution of
HCV genotypes provides information regarding not only the
epidemiology, but also the treatment, of HCV. In a population with a
high risk of repeated HCV infections, the probability of infection
with different HCV genotypes is associated with the speed of changes
of the genotype distribution. We have shown that, in at least 18% of
IDUs with long-term follow-up (up to 7 years), multiple HCV
infections detected by intraindividual changes of the predominant
HCV genotype occurred [6].
It is well known that, in patients infected with multiple HCV
genotypes, one of the infecting virus strains establishes
predominance, and, by use of polymerase chain reaction--based
methods, usually only the actual prevailing strain can be detected
in these patients [7]. However, minor strains do not become
eliminated, and we have demonstrated in various patients that these
minor strains can reappear [6, 8]. These findings are of importance,
especially in the context of therapy with pegylated interferon and
ribavirin. It has been shown that reemergence of minor strains is a
possible cause for failure of therapy [6, 8]. Therefore, the
recommendation was made to repeat genotyping in patients who do not
respond to therapy as expected. This enables adjustment of the
regimen to the actual predominant HCV genotype.
These findings underline the importance of the described dynamic
changes of the epidemiological distribution of HCV genotypes among
IDUs They are important for better understanding (1) the
epidemiology of HCV and (2) possible factors influencing outcome of
therapy.
References
1. van Asten L, Verhaest I, Hernandez-Aguado I, et al. Spread of
hepatitis C virus among European injection drug users infected with
HIV: a phylogenetic analysis. J Infect Dis 2004; 189:292--302.
2. Feucht HH, Schröter M, Zöllner B, Polywka S, Nolte H, Laufs R.
The influence of age on the prevalence of hepatitis C virus subtypes
1a and 1b. J Infect Dis 1997; 175:685--8.
3. Schröter M, Zöllner B, Schäfer P, et al. Epidemiological dynamics
of hepatitis C virus among 747 German individuals: new subtypes on
the advance. J Clin Microbiol 2002; 40:1866--8.
4. Pawlotsky JM, Tsakiris L, Roudot-Thorval F, et al. Relationship
between hepatitis C virus genotypes and sources of infection in
patients with chronic hepatitis C. J Infect Dis 1995; 171:1607--10.
5. Alter MJ, Kruszon-Moran D, Nainan OV, et al. Prevalence of
hepatitis C virus infection in the United States. N Engl J Med 1999;
341:556--62.
6. Schröter M, Zöllner B, Schäfer P, Laufs R, Feucht HH. The rapidly
changing epidemiology of HCV genotypes: consequences for the
individual therapeutic regimen [session WD4]. In: Program and
abstracts of the 11th International Symposium on Viral Hepatitis and
Liver Disease (Sydney). Adelaide: Australian Centre for Hepatitis
Virology, 2003:95.
7. Widell A, Mansson S, Persson NH, Thysell H, Hermodsson S, Blohme
I. Hepatitis C superinfection in hepatitis C virus (HCV)--infected
patients transplanted with an HCV-infected kidney. Transplantation
1995; 60:642--7.
8. Schröter M, Feucht HH, Zöllner B, Schäfer P, Laufs R. Multiple
infections with different HCV genotypes: prevalence and clinical
impact. J Clin Virol 2003; 27:200--4.
J Clin Virol. 2003 Jul;27(2):200-4.
Multiple infections with different HCV genotypes: prevalence and
clinical impact.
Schroter M, Feucht HH, Zollner B, Schafer P, Laufs R.
Institut fur Medizinische Mikrobiologie und Immunologie,
Universitatsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246,
Hamburg, Germany. mschroet@uke.uni-hamburg.de
BACKGROUND: In a HCV genotype 3a-infected patient, viremia with a
different genotype (1b) was detected after 16 weeks of ineffective
therapy. Serological typing revealed that this genotype had already
been present prior to therapy.
OBJECTIVES: To investigate the epidemiology of multiple HCV
infections and the therapeutical consequences for patients
superinfected with a new HCV strain.
METHODS: Sera of 600 patients were screened for infection with
multiple genotypes by using sequencing and a serological assay in
parallel.
RESULTS: Infection with two different HCV types was detected in 13
patients. The prevailing strain was genotyped by sequencing. From
two of these patients additional sera were available which had been
drawn up to 24 and 28 months prior to the current sample,
respectively. Those early samples showed viremia with a HCV subtype
that could not be detected by PCR afterwards. Only antibodies to the
initial strain were detectable in the later samples.
CONCLUSION: In patients serially infected by different HCV strains,
one strain will prevail as the viremic virus. Under antiviral
therapy, the displaced strain may become viremic again and may
influence the outcome of therapy. Detection of inferior strains by
serological assays before antiviral therapy may be important for
choosing the adequate regimen.
http://www.natap.org/
HCV Therapy Should Depend
on Genotype, Doc Says
|
by John C. Martin
|
| |
infection with
hepatitis C
genotype 3 often clears spontaneously,
which can spare the patient unnecessary treatment, according to German
doctors.1
Scientists at Hannover Medical School in Hannover,
Germany and their colleagues who initiated a study on this topic say 15 to
50 percent of untreated patients may experience this type of spontaneous
clearance. "Therefore, factors are needed to identify patients prior to
therapy who have a higher or lower risk for developing a chronic course to
avoid unnecessary
treatment," wrote the researchers, headed
by Heiner Wedemeyer, M.D., in Hannover Medical School's department of
Gastroenterology, Hepatology and Endocrinology.
A Mounting Infection
According to experts, hepatitis C infection has reached epidemic
proportions around the world, accounting for more than 1 million new cases
each year. Four million people in the U.S. alone are infected, and 30,000
new infections are estimated to occur each year. The hepatitis C virus is
classified into various groups, or strains, known as genotypes and
subtypes. Genotype 1, subtype b (genotype 1b) is thought to be more
closely associated with severe
liver disease, and a more aggressive
course than the other HCV genotypes.2
It is also well known that treatment in patients with HCV
genotype 1 is more often unsuccessful compared to patients with genotypes
2 and 3.3 That's why genotype testing is part of a standard
protocol when designing an individual treatment regimen for hepatitis
patients, said Wedemeyer, in an e-mail interview with Priority Healthcare.
This study led to "important new data for the management
of acute HCV," he said.
Homing in on Genotype 3
To further understand the course of hepatitis infection based on genotype,
Wedemeyer and his team evaluated 1,176 inmates at a German prison,
screening them for anti-HCV antibodies. Ninety-two of them tested
positive, the scientists reported. Of those, nearly all reported using IV
drugs for an average of 3 years prior to imprisonment.
Those inmates who tested positive were then genotyped,
and Wedemeyer and his colleagues found that genotype 3 prevalence was
"significantly higher" among inmates who had cleared HCV spontaneously
compared to those who were diagnosed with chronic infection. Specifically,
86 percent of the prisoners with that genotype spontaneously cleared the
virus, compared to 36 percent of those who had chronic infection.
Further, 93 percent of the inmates exposed to HCV
genotype 1 went on to develop chronic infection, compared to just under
two-thirds of those exposed to genotype 3, the researchers noted.
Researchers: Avoid Unnecessary
Treatment
"Thus, acute infection in young Caucasian men with HCV genotype 3 leads
more often to spontaneous clearance than infection with HCV genotype 1,"
the scientists wrote.
Individual treatment strategies for patients with
different genotypes is probably appropriate, based on these findings, said
Wedemeyer. While
chronic infection emerges in the "vast
majority" of genotype 1 cases, unnecessary treatment might be avoided in
those with genotype 3, he said.
"Considering also the high chance of successful
treatment of chronic HCV genotype 3 infection with
pegylated interferon in combination with
ribavirin, we suggest not to treat acute hepatitis C genotype 3 infection
early, but rather to wait at least 3 months after the onset of symptoms
when chronicity becomes likely," wrote Wedemeyer and his team.
It's not exactly known why genotype 3 patients tend to
spontaneously clear the virus compared to other genotypes, Wedemeyer
explained. "It is mostly likely due to the higher sensitivity to type 1
interferons, as we know already for chronic hepatitis C," he said.
1. Lehman M, Meyer MF, Monazahian M, Tillmann HL, Manns
MP, Wedemeyer H. High rate of spontaneous clearance of acute hepatitis C
virus genotype 3 infection. J Med Virol 2004 Jul;73(3):387-91.
2. Zein NN. Clinical significance of hepatitis C virus genotypes. Clin
Microbiol Rev 2000 Apr;13(2):223-35.
3. Viral Hepatitis C. National Center for Infectious Diseases. Centers for
Disease Control and Prevention (CDC).
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.
By Will Boggs, MD
NEW YORK (Reuters Health) Jul 02 - Infection with hepatitis C virus (HCV)
genotype 3 often clears spontaneously, sparing the patient unnecessary
treatment, German researchers report in the July issue of the Journal of
Medical Virology.
Early treatment of patients with acute HCV infection has been advocated
as an approach to preventing chronic infection, the authors point out, but
many patients may clear the virus spontaneously and thus would not require
treatment if they were identified beforehand.
As senior investigator Dr. Heiner Wedemeyer told Reuters Health,
"patients should be genotyped. Wait and see for genotype 3, treat
immediately for genotype 1."
Dr. Wedemeyer from Hannover Medical School and colleagues sought to
determine whether HCV genotype differences could lead to different rates of
spontaneous clearance of acute HCV infection. They studied serum from 92
anti-HCV-positive men in a German prison.
HCV genotype 3 was significantly more common among subjects who were HCV-negative
than among those with HCV viremia, the authors report, and the prevalence of
genotype 3 was even higher after men who were HIV- or hepatitis B-positive
were excluded. Although acute HCV genotype 3 infection spontaneously
resolved in many individuals, most patients (63%) still developed chronic
infection. This rate of chronic HCV was, however, substantially lower than
the rate of chronic HCV infection in those with genotype 1 (93%).
"Considering the high sustained virological response rates of pegylated
interferons plus ribavirin combination therapy of chronic hepatitis C in
patients with genotypes 2 and 3," the authors conclude, "different
strategies for acute HCV infection may be appropriate for different HCV
genotypes."
"Chronicity of acute HCV genotype 1 infection evolves in the vast
majority of cases," Dr. Wedemeyer concluded. "However, unnecessary treatment
can be avoided in genotype 3 infection."
J Med Virol 2004;73:387-391.
http://www.medscape.com/viewarticle/482435_print
Peginterferon alfa-2b and Ribavirin for 24 Weeks
Sufficient for Genotype 2 or 3 Chronic HCV
| Posting Date: June 30, 2004 |
- Phase 4 study: single-arm, open-label,
historical-control study
|
| Summary of Key Conclusions |
- Peginterferon alfa-2b and ribavirin
for 24 weeks highly effective for patients with chronic HCV
genotype 2 or 3 infection
- Genotype 2 patients had a higher
sustained virologic response (SVR)
- Suggests that SVR should be
presented by single genotype rather than grouped
- Further studies needed to test the
efficacy of this treatment schedule in:
- Imunocompromised patients
- HIV/HCV coinfected
- Organ transplant recipients
- Other subgroups
- Patients with persistently normal
ALT
- African Americans
|
| Background |
- Duration of standard treatment in
patients with chronic HCV based on genotype
- Genotype 1: 48 weeks
- Genotype 2 or 3: 24 weeks
- Pegylated interferons associated with
higher sustained virologic response (SVR) rates compared to
standard interferons
- Most trials comparing pegylated to
standard interferons have used 48 weeks of treatment
- Additional studies needed to assess
whether peginterferon-based therapy for genotypes 2 and 3 can be
reduced to 24 weeks without losing antiviral efficacy
- Study conducted to evaluate efficacy
and safety of 24 weeks of peginterferon alfa-2b plus ribavirin in
patients chronically infected with HCV genotype 2 or 3
|
| Summary of Study Design |
- Intent-to-treat analysis
- 224 treatment-naive patients
enrolled
- 81% infected with genotype 3
- Treatment: 24 weeks
- Peginterferon alfa-2b
(subcutaneously)
- Ribavirin (orally)
- 800 mg/day: < 65 kg
- 1000 mg/day: 65-85 kg
- 1200 mg/day: > 85-105 kg
- 1400 mg/day: > 105 kg
- Endpoints evaluated
- Weeks 4, 8, 12, 18, and 24 during
treatment
- Weeks 4, 12, and 24 following end of
treatment (EOT)
- Primary endpoint
- SVR
- Undetectable plasma HCV RNA levels
at 24 weeks following EOT
- Secondary endpoint
- SVR and normalization of ALT at 24
weeks following EOT
- Statistical analysis
- Prediction model developed based on
previously published data
- Prognostic factors used
- Genotype
- Baseline HCV-RNA level
- Presence or absence of bridging
fibrosis (F3) or cirrhosis (F4)
- Age
- Gender
|
| Baseline Characteristics |
- Demographic characteristics
- Total: 224
- Caucasian: 211 (94%)
- Mean body weight: 75.7 kg
- Mean age: 39.9 years
- Risk factor for transmission
- Parenteral: 132 (59%)
- Transfusion: 28 (13%)
- Sporadic/other: 64 (29%)
- Mean number of years since exposure:
15.5
- Biochemical characteristics
- Molecular parameters
- Genotype 2: 42 (19%)
- Genotype 3: 182 (81%)
- Mean pretreatment log10
HCV RNA: 5.55 IU/ml
- Histologic profile
- Mean Knodell score
- 1 (periportal bridging necrosis):
2.6
- 2 (parenchymal injury): 1.7
- 3 (portal inflammation): 2.5
- 1 + 2 + 3 (total inflammation):
6.8
- 4 (fibrosis): 1.5
- Steatosis (genotype 2/genotype 3)
- 0: 16/33 (38%/18%)
- > 0-5: 20/63 (48%/35%)
- > 5-32%: 6/53 (14%/29%)
- > 32%-66%: 0/17 (0%/9%)
- > 66% 0/10 (0%/6%)
- Missing: 0/6 (0%/3%)
|
| Main Findings |
- Overall virologic response rates
- EOT : 211/224 (94%)
- SVR: 182/224 (81%)
- Comparisons
- Higher EOT for genotype 2 compared
to genotype 3 (100% vs 93%)
- Higher SVR for genotype 2 compared
to genotype 3 (93% vs 79%)
- Higher relapse rates
- Male (16% vs 7%)
- Age > 55 years (27% vs 12%)
- Steatosis > 32% (23% vs 11%)
- Genotype 3 (14% vs 7%)
- Baseline HCV RNA > 600,000 IU/mL
(20% vs 7%)
- Efficacy of 24-week treatment schedule
confirmed
- Based on model that predicted a SVR
rate of 84.4% for 48 weeks of treatment
- Normal ALT and undetectable HCV RNA at
end of follow-up
|
| Other Outcomes |
- Predictors of response (stepwise
multivariable logistic regression analysis)
- Baseline HCV RNA level (P =
.026)
- ¡Ý16 weeks of treatment (P =
.0003)
- Steatosis < 5% (P = .012)
- Adverse events
- Serious
- During treatment: 6%
- During follow-up: 3%
- Reasons for treatment discontinuation
- Adverse events: 11
- Depression: 4
- Neutropenia: 2
- Thrombocytopenia: 2
- Tooth abscess, musculoskeletal pain,
hyperthyroidism: 1 each
Zeuzem S, Hultcrantz R, Bourliere M, et al.
Peginterferon alfa-2b plus ribavirin for treatment of chronic
hepatitis C in previously untreated patients infected with HCV
genotypes 2 or 3. J Hepatol. 2004;40:993-999.
|
http://www.clinicaloptions.com/hep//jopt/articles/article.asp?a=Zeuzem-JHep-2004-06&page=capsule
Evidence for a Relation Between the
HCV Viral Load and Genotype and HCV-specific T Cell Responses
The reason why patients
with hepatitis C virus (HCV)
genotype non-1 infection respond better to antiviral therapy than
patients with genotype 1 infection is not known. The aim of this study is to
explore the relation between the viral genotype, viral load, and the
endogenous T cell response.
The viral genotype, the
viral load, and the endogenous proliferative T cell response to the
non-structural 3 protein (NS3) was analyzed using serum and peripheral blood
mononuclear cells from 103 patients with chronic HCV infection.
Results
Among 71 non-treated
patients, a T cell response was more common among those infected by genotype
3, as compared to those infected with genotype 1 (P<0.05). Among 32 patients
undergoing antiviral therapy, presence of a T cell response was more common
in genotype non-1 infected patients than in those infected by genotype 1
(P<0.01).
Presence of a T cell
response was related to a more rapid viral clearance (P<0,05), a negative
HCV RNA test at week 12 (P<0.05), and a shorter viral half-life (P<0.05).
Conclusion
The presence of an
NS3-specific T cell response is related to the viral genotype and to a more
rapid clearance of HCV RNA during antiviral therapy.
06/14/04
Reference
C Hultgren
and others. Evidence for a
relation between the viral load and genotype and hepatitis C virus-specific
T cell responses. Journal of Hepatology 40(6): 971-978. June 2004.
Link to Index
of all HCV articles
Peginterferon Alfa-2b (Peg-Intron)
plus Ribavirin Treatment in Previously Untreated Patients Infected with
HCV Genotype 2 or 3
Patients infected with chronic hepatitis C
genotype 2 or 3 were treated effectively with 24 weeks of
Peg-Intron
(peginterferon alfa-2b) and Rebetol (ribavirin) combination
therapy, according to results of a study published in the June 2004
issue of the Journal of Hepatology.
The study reports that
81 percent of patients overall (93 percent for genotype 2 and 79 percent for
genotype 3) achieved a
sustained
virologic response (SVR).
Not surprisingly, the
study also showed that the shorter treatment regimen was better tolerated by
patients as compared with a 48-week historical control group. Data from the
study were first presented in part at the
54th
Annual Meeting of the American Association for the Study of Liver Diseases
(AASLD), October 24-28, 2003, Boston, MA, USA.
In the era of conventional
interferon alfa plus ribavirin, treatment duration in patients with chronic
hepatitis C was tailored according to hepatitis C virus (HCV) genotype:
patients infected with HCV-1 were treated for 48 weeks, patients infected
with HCV-2/3 for 24 weeks. The aim of the present study was to investigate
this schedule for HCV-2/3 infected patients in the era of pegylated
interferon alfa plus ribavirin.
Patients chronically
infected with HCV-2 (n=42) or HCV-3 (n=182) were treated with
peginterferon alfa-2b (PEG-Intron) 1.5 microgram/kg subcutaneously once
weekly plus ribavirin 800-1400 mg/day based on body weight for 24 weeks
Results
The end of treatment (EOT)
and sustained virologic response (SVR) was higher in patients infected with
HCV-2 (100 and 93%, respectively) than in patients infected with HCV-3 (93
and 79%, respectively). Baseline viremia (P=0.020), treatment
duration >16 weeks (P<0.001) and steatosis (<5%, P=0.015) were
significant independent predictors of SVR.
Adverse events resulted in
discontinuation in 5% and dose reduction in 22% of patients.
Conclusions
Treatment for 24 weeks
with peginterferon alfa-2b and ribavirin is sufficient in HCV 2 or 3
infected patients. The lower SVR in patients infected with HCV-3 compared
with HCV-2 infected patients may be related to higher levels of steatosis in
this population.
This study suggests that
genotype 2 patients and genotype 3 patients are not the same, with genotype
3 patients with high viral load [emphasis added] being more difficult
to treat and perhaps requiring 48-week therapy to achieve SVR.
Commentary
Principal study
author Professor Stefan Zeuzem, MD, of Saarland University in Homburg,
Germany noted, “The results of this study are important for two reasons.
First, the study reinforces the point that shorter treatment durations can
be effective for specific hepatitis C patient groups. Second, the
study provides new evidence to support a rationale for an individualized
approach to treatment.”
The finding in this study
that genotype 3 patients with high viral loads are more difficult to treat
confounds previous data reporting genotypes 2 and 3 results lumped together
in one percentage. Schering-Plough has submitted data from this study
to the CPMP seeking a label change in the European Union.
06/02/04
Reference
S
Zeuzem and others. Peginterferon alfa-2b plus ribavirin for treatment of
chronic hepatitis C in previously untreated patients infected with HCV
genotypes 2 or 3.
Journal of Hepatology 40
(6): 993-999. June 2004.
Hepatitis C Virus Genotype 3 Infection May Resolve Spontaneously
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