Tuesday Posters (11/15/2005)– HCV Treatment – 8:00AM – 6:30PM
Abstract ID: 65089
Category: JO7: HCV:
Treatment
Assessment of ribavirin mutagenic properties in vivo and the influence of interferon alpha-induced reduction of hepatitis C virus RNA load upon therapy.
S. Chevaliez, Hopital
Henri Mondor, Universite Paris 12, Creteil, France, R. Brillet, Hopital Henri
Mondor, Universite Paris 12, Creteil, France, C. Hezode, Hopital Henri Mondor,
Universite Paris 12, Creteil, France, D. Dhumeaux, Hopital Henri Mondor,
Universite Paris 12, Creteil, France, J. Pawlotsky, Hopital Henri Mondor,
Universite Paris 12, Creteil, France
In a recent report (Nature 2004;432:922-924), mathematical
modeling of viral load decay during IFN alpha-ribavirin therapy was used to
suggest that ribavirin primarily acts by making HCV virions produced during
therapy less infectious. The hypotheses raised to explain this effect were
that: (i) ribavirin, by being mutagenic, would accelerate the accumulation of
genome mutations leading to the increased generation of non viable HCV variants
(so-called ‘error catastrophe’); (ii) ribavirin’s mutagenic effect would appear
only in patients with a low viral production related to a high antiviral
efficacy of IFN.
OBJECTIVE:
To test these hypotheses in patients with chronic hepatitis C
receiving IFN plus ribavirin.
METHODS:
The HCV genes encoding the full-length NS3 protease and
full-length NS5A protein were
PCR-amplified 14 days before treatment, at baseline, at day 14 and at day 28 of
therapy in 4 patients receiving ribavirin only and in 5 patients treated with IFN
alpha 2b-ribavirin combination. Extensive quasispecies analysis was performed
on the basis of 1360 clones generated and sequenced.
RESULTS:
(I) In the patients receiving ribavirin monotherapy, the rate
of accumulation of mutations did not accelerate during ribavirin administration
compared to the pretreatment period (natural genetic drift). In contrast, it
tended to slow in 2 cases. (ii) In 4 of the 5 patients under IFN-ribavirin
combination therapy, who all experienced a sharp reduction of viral replication
over the study period, the rate of accumulation of mutations did not accelerate
during the first 14 days of treatment compared to pretreatment, nor did it
accelerate during the following 14 days when HCV RNA was consistently reduced
by IFN. (iii) In one patient, however, the rate of accumulation of mutations
exponentially accelerated during treatment, with a very high mutation rate
between day 14 and day 28 when the HCV RNA load decreased from 45,000 down to
200 IU/ml (ie just before becoming negative). Two hypotheses can explain this
finding: a- an artefact related to the selection of minor variants due to the
very low viral load; b- an accelerated mutagenesis by ribavirin in the context
of profound HCV RNA suppression as suggested by mathematical modeling. The
latter hypothesis is currently being tested by analyzing the last HCV
RNA-positive sample in each patient.
CONCLUSIONS:
Ribavirin does not appear to be a mutagenic agent in vivo,
either in monotherapy or in combination with IFN alpha. However, this property
could be revealed when HCV replication is reduced to very low levels by IFN, a
hypothesis currently under study (these results will be presented).
Abstract ID: 65416
Category: JO7: HCV:
Treatment
Clinical and Economic Implications of a 4-Week Viral Negative Response to Peginterferon Alfa-2b plus Ribavirin for Chronic Hepatitis C and Genotype 1 with Low Viral Load.
J. B. Wong, Tufts-New
England Medical Center, Boston, MA, S. Zeuzem, Saarland University Hospital,
Homburg/Saar, Germany, M. P. Manns, Medizinische Hochschule Hannover, Hannover,
Germany, J. Harvey, Schering Plough Research Institute, Kenilworth, NJ, J. K.
Albrecht, Schering Plough Research Institute, Kenilworth, NJ
Introduction:
For chronic hepatitis C infections with genotype 1, monitoring
viral response at week 12 during treatment with peginterferon a-2b plus
ribavirin has become the standard management algorithm, permitting
discontinuation in those unlikely to achieve a sustained viral response (SVR).
An earlier week 4 viral negative response to therapy identifies a subgroup of
patients with genotype 1 and low viral load (£2 million copies/ml) who can be
treated for just 24 weeks.
Aim:
To estimate the clinical and economic consequences of a
4-week viral negative response to peginterferon a-2b plus ribavirin for
patients with genotype 1 and low viral load.
Methods:
We analyzed two trials of peginterferon a-2b plus ribavirin
involving genotype 1 patients with low viral load (Manns Lancet 2001, Zeuzem
EASL 2005). Although both trials dosed peginterferon a-2b at 1.5 mg/kg/week,
they differed in the ribavirin dose and intended duration of therapy: ribavirin
800 mg/day (>10.6 mg/kg) for 48 weeks in Manns and ribavirin 800-1400 mg/day
for 24 weeks in Zeuzem. We examined 4-week virologic and SVR outcomes. Drug
costs were based on US average wholesale drug costs and observed dosages and
duration of therapy in these trials.
Results:
The table shows the viral response data. For genotype 1
patients with low viral loads treated for 24 weeks, a 4-week viral negative
response occured in 46% (95% CI: 39-54%) with an 89% (95% CI: 79-95%)
likelihood of SVR (predictive value positive). The 4-week viral negative
response should not be used as a stopping criteria because many sustained
responders are not viral negative at week 4 (predictive value
negative<100%).
|
|
24
weeks |
48
weeks |
|
Viral Negative Week |
4 110/235 (46%) |
13/38 (35%) |
|
Likelihood of SVR |
98/110 (89%) |
11/13 (85%) |
|
Predictive Value Negative |
96/115 (83%) |
9/25 (36%) |
Drug costs for those viral negative at week 4 were $16,784
using the observed adherence to dosages and therapy duration in the 24 week
study. Assuming the same adherence estimates for 48 weeks, drug costs would
double to $33,567. If instead drug use matched that observed in the 48 week
study, drug costs would equal $23,036 so that limiting treatment to 24 weeks
would reduce costs by $6252, a 27% savings. Discontinuations (14% vs 3%) and
dose reductions (49% vs 25%) were more frequent in the 48 week than in the 24
week trial, so the 27% likely represents a minimum savings.
Conclusion:
A viral negative response at week 4 in genotype 1 patients
with low viral load identifies those who can be treated for just 24 weeks with a
high likelihood of achieving a sustained viral response.
Abstract ID: 65792
Category: JO7: HCV:
Treatment
INCIDENCE OF INFECTIONS DURING COMBINATION TREATMENT OF CHRONIC HEPATITIS C WITH PEGYLATED INTERFERONS ALFA 2B and 2A.
M. Antonini, University of
Brescia, Brescia, Italy, M. Puoti, University of Brescia, Italy, Brescia,
Italy, S. Babudieri, Clinica Malattie Infettive, Sassari, Italy, B. Zanini,
Clinica di Malattie Infettive, University of Brescia, Brescia, Italy, P.
Pagani, Clinica di Malattie Infettive, University of Brescia, Brescia, Italy,
S. Rossi, Clinica di Malattie Infettive, AO Spedali Civili, Brescia, Italy, I.
Maida, Clinica di Malattie Infettive, University of Sassari, Sassari, Italy, V.
Putzolu, Clinica di Malattie Infettive, University of Brescia, Brescia, Italy,
C. Baiguera, Clinica di Malattie Infettive, University of Brescia, Brescia, L.
Fenu, Clinica di Malattie Infettive, University of Sassari, Sassari, Italy, S.
Zaltron, Clinica di Malattie Infettive, AO Spedali Civili, Brescia, Italy, A.
Spinetti, Clinica di Malattie Infettive, AO Spedali Civili, Brescia, Italy, L.
Biasi, Clinica di Malattie Infettive, AO Spedali Civili, Brescia, Italy, S.
Sassu, Clinica Di Malattie Infettive, University of Sassari, Sassari, Italy, K.
Prestini, Clinica di Malattie Infettive, University of Brescia, Brescia, Italy,
F. Zacchi, Clinica di Malattie Infettive, University of Brescia, Brescia,
Italy, G. Carosi, Clinica di Malattie Infettive, University of Brescia,
Brescia, Italy, M. Mura, Clinica di Malattie Infettive, University of Sassari,
Sassari, Italy
To evaluate incidence and risk factors for neutropenia and
infections occurring during combination therapy for chronic hepatitis C with
pegylated interferons (PEGIFN)s and ribavirin we analysed longitudinal data
from two Italian reference centres. Complete blood count was performed 1, 2 and
4 after starting treatment and then every 4 weeks thereafter but every week if
neutrophils (N) counts<1000/mL. Dose adjustments for neutropenia were made
according to manufacturers’ instructions. The analysis included all consecutive
HCV infected patients without HIV co-infection who were prescribed PEGIFNs from
June 1st 2001 to December 31st 2004. Mann-Whitney, Fisher’s exact test Log Rank
test and Cox’s proportional model were used to assess statistical associations.
We studied 319 patients treated for chronic hepatitis C with once weekly
PEGIFNs: 2b 12 KDa at 1.5 mg/kg (162) or 2a 40KDa at 180 mg flat dose (157), in
combination with ribavirin 10.6-13 mg/kg/d,. Patients treated with PEGIFNa2a
had a significantly higher prevalence of F3-F4 stages at liver biopsy (62% vs.
33%; p<0.0001) showed a significantly higher body weight (72 vs 68 Kg
p=0.03), significantly lower baseline N counts (2.97 vs. 3.3 x103 mL p=0.03) and
were treated for a significantly longer time period (mean 190 vs 175 days
p=0.006). We observed 73 infections: 38 in patients treated with PEGIFNa2b and
35 in patients treated with PEGIFNa2a. Twenty-three were respiratory
infections, 17 cellulitis, 13 dental abscesses, 2 gastro-enteric infections and
18 infections involving other sites. Most of infections were mild; only four
patients (1.2%) required hospitalisation. Proportion of treatment duration with
N< 800/ mL were not significantly different in the two treatment groups
(2.3% vs. 4%) Incidence of neutropenia and infections in persons treated with
PEGIFNa2awere not related to body weight.. No statistically significant
difference in the incidence of all infections and neutropenia was observed
between patients treated with the two PEGIFNs. The incidence of all infections
was significantly associated with age (HR 1.03 per year 95% CI 1.01- 1.05
p<0.001). Incidence of respiratory infection was related with duration of
neutropenia (N< 800/mL) HR 1.013 per day (95% CI 1.0036-1.0225; p=0.0069)
and with usage of PEGIFNa2b HR 2.45 (95% CI 1.001-6.01; p=0.041) but not with
age. Incidence of severe infections was low. However 23% of treated patients
suffered for infectious episodes with an increasing risk in aged subjects.
Respiratory infections were related to the duration of neutropenia and there
was a trend for an independent association between usage of PEGIFNa2b and
respiratory infections.
Abstract ID: 65859
Category: JO7: HCV:
Treatment
Does Hepatic Steatosis affect Sustained Virological Response in chronic Hepatitis C genotype 3 infected patients?
S. Rasool, Department of
Medicine, Karachi, Pakistan, S. Hamid, The Aga Khan University,, Karachi, M.
Zubair, Aga Khan University, Karachi, Pakistan, K. Mumtaz, Aga Khan University,
Karachi, Pakistan, H. Shah, Aga Khan University, Karachi, Pakistan, W. Jafri,
Aga Khan University, Karachi, Pakistan
Hepatic steatosis can be a prominent feature of chronic
hepatitis C virus (HCV) infection, especially in genotype 3 patients, and is
considered to be an independent factor for treatment failure. However, the
association of this observation with different genotypes is not clear.
Prevalence of genotype 3 is very high among chronic HCV patients in our
community (in the range of 85%-90%).
Objectives:
The purpose of this study was to define the role of steatosis
on sustained virological response (SVR) to antiviral therapy in chronic
hepatitis C genotype 3 patients.
Methods:
We analyzed all naïve chronic HCV patients treated in our department
during the last four years. Patients were included in the study only if a
pretreatment liver histopathology was available, were infected with HCV
Genotype 3 patients, completed 6 months of therapy with interferon-α
and ribavirin and had follow up available of at least 6 months. Liver biopsies
were graded according to HAI and steatosis according to Brunt et al.
Results:
A total of 98 eligible patients were studied. Mean age was
38.09±9.02 years and sixty (61%) were males. Steatosis was present in
67/98(68.3 %) of patients. It was mild in 35/98 (35.7%) and moderate to severe
in 32/98 (32.6%) of patients. End treatment response was achieved in 65/98
(66.3%) and SVR in 62/98 (63.3%) patients. SVR was associated with stage of
fibrosis (p=0.02) and pre-treatment platelet count (p=0.05) but was not
associated with age (p=0.92), gender (p=0.39), BMI (p=0.74), grade of
inflammation (0.53) and grade of steatosis (0.28).
Conclusion:
Hepatic steatosis is present in a significant number of
patients with chronic hepatitis C genotype 3 infection but does not affect
sustained virological response.
Abstract ID: 65996
Category: JO7: HCV:
Treatment
Evidence of saturable ribavirin absorption.
K. Lindahl, Div of Infectious
Diseases, I 73, Stockholm, Sweden, R. Schvarcz, Div of Infectious Diseases,
I73, Stockholm, Sweden, L. Ståhle, Dep of Clinical Pharmacology, Stockholm,
Sweden
Aims:
Ribavirin is a nucleoside analogue most commonly used in
combinations therapy with interferon for the treatment of chronic hepatitis C.
Currently dose escalation studies are carried out and the aim of this study was
to analyse the effect of dose on the bioavailability of ribavirin to study the
possibility of saturable absorption. The authors also investigated the
stability of ribavirin blood samples.
Methods:
Twenty-four patients treated for chronic hepatitis C were
included in the study, 10 of which were obtained from a recent study of higher
doses than used in current European guidelines. Ribavirin concentrations were
analysed with a HPLC method. Relative bioavailability was defined as the
observed concentration at steady state divided by the predicted concentration
using a model previously described in a population pharmacokinetic analysis.
Ribavirin stability was studied in whole blood samples obtained from four
patients and stored under different conditions.
Results and conclusion:
Higher ribavirin doses were found to be linearly associated
with a lower bioavailability (r2= 0.36; p<0.01). At the highest dose, the
bioavailability was reduced by 50%. The main finding in this study is that the
bioavailability of ribavirin gradually declines with increasing doses. These
data suggests that ribavirin absorption is saturable and that ribavirin should
be dosed at least thrice daily if higher doses, than recommended in most
current guidelines, are used. It is also shown that there is a markedly
increase of ribavirin concentration in whole blood samples stored for longer
time at room temperature. The ribavirin concentration increased approximately
five times when stored for one week at
room temperature before centrifuged and frozen, compared to ribavirin
concentrations analysed within 3 hours. The recommended practice is to separate
plasma and store samples frozen within 24 hours.
Abstract ID: 66252
Category: JO7: HCV:
Treatment
Factors Associated with Liver Clinic Referral of Hepatitis C Virus (HCV)-Infected Patients.
H. Al-Hashem, Yale
University/VA-CT Hepatitis C Resource Center, New Haven, CT, S.
Wongcharatrawee, Yale University/VA CT- Hepatitis C Resource Center, New Haven,
CT, J. Stratidis, Yale University/VA CT- Hepatitis C Resource Center, New
Haven, CT, G. Garcia-Tsao, Yale University/VA CT- Hepatitis C Resource Center,
West Haven, CT
Screening and testing for HCV is a priority at the VA
Healthcare System with the ultimate goal of increasing the number of HCV
patients who have appropriate information and timely access to medical
evaluation, enabling them to reach a decision regarding antiviral therapy.
Reaching this goal depends on appropriate referral to providers who treat HCV.
Objective:
To determine the rate of referral of HCV patients to the
liver clinic and to determine predictors associated with referral.
Methods:
Retrospective cohort study of HCV-infected veterans
identified in the period between September 1, 2003 and June 30, 2004 using the
local HCV registry that contains data on patients with positive anti-HCV test
or an HCV diagnosis. Prior to this period, several provider-training sessions
regarding appropriate referral to liver clinic took place among local
providers, particularly those from mental health clinics.
Results:
Of 235 patients identified, 34 were excluded because of a
negative confirmatory test (prior to referral). The study comprises 201
HCV-infected patients with a median age of 52 years; 95% were male and 62% were
Caucasian; 83% had a history of substance use and/or mental illness. Only 100
(50%) were referred to the liver clinic. Compared to non-referred patients,
those referred were more likely to have an assigned primary care provider (PCP)
(78% vs. 57%, p=0.002), be referred from a primary care clinic (PCC) (82% vs.
61%, p=0.002), have documented risk factors (89% vs. 62%, p<0.001) and have
abnormal liver tests (LT) (66% vs. 34%, p<0.0001). There were no differences
between groups regarding age, race, type of provider (MD vs. non-MD), and
presence of medical or psychiatric co-morbidities. Independently predictive
determinants of referral (stepwise logistic regression) were referral from PCC
and abnormal LT. Analysis of the subgroup of patients with abnormal LT (n=102)
reveals that only 66 (65%) were referred. Compared to non-referred patients,
those referred were more likely to have an assigned PCP (82% vs. 50%, p=0.001),
be referred from a PCC (82% vs. 56%, p=0.006) and have documented risk factors
(91% vs. 75%, p=0.032). On multivariable analysis, the strongest predictor of
referral of patients with abnormal LT was having an assigned PCP.
Conclusions:
At a VA facility, only half of HCV-infected patients are
referred to liver clinic. The main predictors of referral (both in all HCV
patients and in those with abnormal LT) were related to patient enrollment in
the PCC. Future efforts should be aimed at ensuring enrollment of all veterans
in a primary care clinic and at creating referral electronic reminders for
primary care providers.
Abstract ID: 67446
Category: JO7: HCV:
Treatment
Ribavirin plasma concentration is predictive of sustained virological response in HCV infected patients. A prospective study.
D. Breilh, Hopital Haut
Leveque, Pessac, France, L. Castera, Hopital Haut-Leveque, Pessac, France, P.
Trimoulet, Hopital Pellegrin, Bordeaux, France, J. Foucher, Hopital
haut-Leveque, Pessac, France, S. Djabarouti, Hopital Haut Leveque, Pessac,
France, P. Bernard, Hopital Saint-Andre, Bordeaux, France, J. Bertet, Hopital
Haut Leveque, Pessac, France, P. Couzigou, Hopital Haut Leveque, Pessac,
France, M. Saux, Hopital Haut-Leveque, Pessac, France, V. de Ledinghen, Hopital
Haut-Leveque, Pessac, France
Background & aims:
Combination therapy with pegylated interferon and ribavirin
is the standard treatment for chronic hepatitis C virus (HCV) infection.
However, a relationship between virological response and ribavirin
concentration has been previously reported. The aim of this prospective study
was to define the target ribavirin concentration at week 12 associated with
virological response at week 12, and 6 months after the end of treatment
(sustained virological response, SVR).
Methods:
HCV infected naïve consecutive patients treated with standard
regimen of pegylated interferon and ribavirin (800-1200 mg/day, according to
genotype) were assessed for ribavirin plasma concentration at week 12. Residual
plasma ribavirin concentration (12 hours after the previous dose) was obtained
using a validated high performance liquid chromatography assay. Response at
week 12 was defined as undetectable HCV-RNA or HCV-RNA drop ≥ 2 Log.
Results:
56 patients (19 males, mean age 50 ± 12 years, genotype 1
52%, mean viral load 912000 ± 1260000 UI/l) were included. Response at week 12,
and SVR were observed in 80%, and 67.5% of patients, respectively. Median
ribavirin plasma concentration at week 12 was 3.19 mg/l (range:0.41-7.23).
Responders at week 12 and SVR had significantly higher plasma ribavirin
concentration at week 12 than non responders: 3.29 vs 2.85 mg/l (p=0.005), and
3.47 vs 2.85 mg/l (p=0.023), respectively. A Chi2 step by step analysis
indicated that the threshold of 3 mg/l at week 12 gave the best sensitivity
(65.4%) and specificity (64.3%) for SVR. Using this threshold, ribavirin plasma
concentration at week 12 had positive predictive value of 77% for SVR.
Conclusion.
Patients with SVR had higher ribavirin plasma concentration
at week 12 than non-responders. Three in four patients with a concentration
higher than 3 mg/l at week 12 were SVR. Therefore, early determination during
treatment of plasma ribavirin concentration (with a target concentration of 3
mg/l at week 12) could be useful for monitoring HCV therapy. The impact of
ribavirin dosage optimization, to obtain such a target concentration, on SVR
rates should be further investigated.
Abstract ID: 67955
Category: JO7: HCV:
Treatment
High Frequency of Anemia in HCV-HIV Coinfected Persons Receiving Weight-based Ribavirin and Zidovudine.
K. E. Sherman, University
of Cincinnati College of Medicine, Cincinnati, OH
Among patients with HCV infection, treatment with
Pegylated-Interferon (PEG-IFN) and Ribavirin (RBV) is often associated with
anemia due to a combination of marrow suppression and ribavirin-induced
hemolytic anemia. Anemia may lead to dose reduction and/or use of growth
factors (e.g. epopoietin). Despite a tendency towards anemia among HCV/HIV
coinfected subjects prior to PEG-IFN/RBV administration, previous studies
suggested relatively good tolerability when ribavirin was administered at a
dose of 800 mg/day. There is little data regarding treatment-associated anemia
when weight-based ribavirin dosing is utilized. An unexpected degree of anemia
in ACTG 5178 was observed and further analyses were performed.
METHODS:
ACTG 5178 is a PEG-IFN/RBV treatment trial for subjects with
HCV/HIV coinfection. Inclusion criteria
mandated hemoglobin (HGB) of >11 g/dl for men and >10 g/dl for women. All
patients must have been on stable ART for 8 weeks prior to entry. All subjects
were treated with PEG-IFN alfa 2a 180 mcg q week + ribavirin 1000/1200 mg/day
based upon body weight. Toxicity grade for change in HGB level was determined
according to standard DAIDS/ACTG criteria.
RESULTS:
50 enrolled subjects had baseline and at least one subsequent
on-treatment HGB determination. Following study drug initiation, twelve subjects
(24.5%) had Grade 1 or greater anemia. Of these four reported Grade 2 anemia.
Forty percent of subjects were on ART containing ZDV at entry. Among the 20
subjects actively receiving ZDV, eight (40%) had anemia meeting at least Grade
1 criteria. In contrast, only 4/30 (13.3%) of subjects not on concurrent ZDV
had Grade 1 or greater anemia (P= 0.04). Dose modification of ribavirin was
noted in 13 subjects. The majority (9) cited anemia as the reason for a change
of ribavirin dosing.
CONCLUSION:
Unexpectedly high levels of anemia and ribavirin dose
reduction were observed following initiation of ACTG 5178 compared to other
treatment trials utilizing a lower dose of ribavirin. Data analysis suggests
that concomitant ZDV use is highly associated with a higher frequency of Grade
1 or higher anemia compared to subjects on other drug-containing regimens.
Increased early monitoring of HGB in these patients is recommended.
Abstract ID: 65345
Category: JO7: HCV:
Treatment
Baseline neutralizing responses predict the virological response to pegylated interferon alpha-ribavirin combination therapy.
P. Woerther, Hopital Henri
Mondor, Universite Paris 12, Creteil, France, Y. Morice, Hopital Henri Mondor,
Universite Paris 12, Creteil, France, L. Barbotte, Hopital Henri Mondor,
Universite Paris 12, Creteil, France, F. Montestruc, Roche Laboratories,
Neuilly-sur-Seine, France, D. Lavillette, Ecole Normale Superieure, Lyon,
France, M. Bouvier-Alias, Hopital Henri Mondor, Universite Paris 12, Creteil,
France, J. Bronowicki, Hôpital Brabois, Nancy, France, C. Hezode, Hopital Henri
Mondor, Universite Paris 12, Creteil, France, I. Lonjon-Domanec, Roche
Laboratories, Neuillysur- Seine, France, B. Bartosch, Ecole Normale Superieure,
Lyon, France, F. Cosset, Ecole Normale Superieure, Lyon, France, J. Pawlotsky,
Hopital Henri Mondor, Universite Paris 12, Creteil, France
The mechanisms underlying the success or failure of pegylated
interferon (PegIFN)-ribavirin combination therapy in chronic hepatitis C are
multifactorial, intricate, and poorly understood. Virological and host factors
have been studied, but the role of anti-HCV humoral responses (in particular
the neutralizing response) remains unknown, mainly due to the lack of reliable
assays.
OBJECTIVES:
To determine the relationship between anti-HCV neutralizing
responses and baseline parameters and the virological responses to
pegIFN-ribavirin therapy.
METHODS:
524 patients with genotype 1 chronic hepatitis C were treated
with a combination of PegIFN-alpha 2a (Pegasys, Roche), 180microg qw, and
ribavirin (Copegus,), 0.8 g/d. At week 24 the virological responders(HCV RNA
negative) were randomized into continuing on combination therapy or on pegIFN
alone. Serum neutralizing activity was measured at baseline by means of arecently
developed in vitro neutralization assay based on the use of infectious
retroviral pseudo-particles expressing the folded HCV envelope glycoproteins at
their surface. This assay was optimized for high throughput and intrinsic
performance.
RESULTS:
Results are available for 179 patients (the final results
with the 524 patients will be presented). Neutralizing responses ranged from 0
(no detectable neutralizing response) to 100% (complete neutralization of HCV
pseudoparticles infectivity in vitro by serum). Multivariate analysis showed a
significant relationship between baseline neutralizing responses and the age
(more or less than 44 years, p=0.0352) and the occurrence of a 2 log HCV RNA
decrease at week 2 of therapy (p=0.0018). Both variables interacted, so that
the relationship between baseline neutralizing response and the virological
response at week 2 was stronger in the patients under 44 years of age (less
than 44 years: 70.4% [65.0%-75.8%] in more than 2 log responders vs 85.0%
[79.1%-91.0%] in less than 2 log responders; more than 44 years: 81.6%
[76.9%-86.3%] vs 85.4% [78.9%-91.8%]). The baseline neutralizing response was
also significantly related to the virological response (negative HCV RNA) at
week 24 and to the sustained virological response in univariate analysis, but
both responses were related to the virological response at week 2 which had the
strongest relationship in multivariate analysis.
CONCLUSION:
Baseline neutralizing activity of HCV genotype 1-infected
patients is significantly related to the age and the virological response to
pegIFN-ribavirin therapy. A weaker neutralizing activity is associated with a
more rapid HCV RNA decline and a greater likelihood of a sustained virological
response.
Abstract ID: 63189
Category: JO7: HCV:
Treatment
Expectant management of chronic hepatitis C infection – the patient perspective.
O. S. Khokhar, University
of Illinois College of Medicine - Peoria, Peoria, IL, J. H. Lewis, Georgetown
University Medical Center, Washington, DC
OBJECTIVE:
To assess patient satisfaction and the rationale behind the
informed decision to be treated expectantly for chronic hepatitis C virus (CHC)
infection.
METHODS:
A retrospective open access clinic-based chart review was completed
on all patients with ICD-9 code 070.54 generated from hospital billing
databases. Variables that were recorded included patient demographics, liver
biopsy results, liver imaging results, peak alanine transaminase (ALT) level,
comorbid conditions, source of infection, duration of infection, and rationale
for expectant treatment by patient. A follow-up telephone communication
consisting of a structured questionnaire was made at least one year after
initial consultation was done. Patients were asked about their current health
status, confirmation of expectant management, and awareness of pegylated
interferon.
RESULTS:
A total of 446 patient charts were reviewed. Out of these,
115 (26%) patients made an informed choice for expectant management after consultation.
Sixty-eight patients (59%) were genotype 1A, and 37 (32%) were genotype 1B. The
remaining ten patients were genotype 3A, 3B, 2A, 2B, or 4. The major reasons
for choosing expectant management were: the absence of any symptoms [n=51
(44.3%)]; concerns regarding adverse effects [n=25 (21.7%)]; medical
contraindications [n=23 (20.0%)]; social circumstances interfering with
effective treatment [n=11 (9.6%)]; and doubts regarding efficacy [n=5 (4.3%)].
A total of 75 patients were successfully contacted. Fifty-eight patients (77.3%
[95% CI, 67.8% - 87.8%]) were comfortable with their initial decision and
wished to remain expectantly followed. Eight patients (10.7% [95% CI, 3.7% -
17.7%]) stated that they were moderately satisfied, and six (8.0%) patients
expressed dissatisfaction with their decision. Two patients (2.7%) had since
chosen interferon treatment, while one patient died while awaiting transplant.
CONCLUSIONS:
A significant majority of patients with HCV infection choose
to be followed expectantly. Reasons for this important decision include the
asymptomatic nature of infection, concern of adverse effects and efficacy,
medical contraindications, and social circumstances preventing optimal
treatment. Furthermore, it is noted that the majority of patients remained
satisfied with their initial informed decision to be followed expectantly.
Based on our findings, we recommend that candidates for interferon treatment
continue to be educated regarding efficacy and adverse effects. In addition,
patients with changeable social conditions preventing treatment should be
closely monitored for resolution of those issues and reevaluation.
Abstract ID: 63583
Category: JO7: HCV:
Treatment
Efficacy of Peginterferon alfa-2a (40KD) and Ribavirin in patients with chronic hepatitis C in Germany – a contribution to health care research.
E. Zehnter, Centre of
Gastroenterology Dortmund, Dortmund, Germany, S. Mauss, Centre of
Gastroenterology and Hepatology, Düsseldorf, Germany, C. John , Centre of
Gastroenterology Dr. John, Berlin, Germany, R. Heyne , Centre of
Gastroenterology Dr. Heyne, Berlin, Germany, B. Möller , Centre of
Gastroenterology, Dr. Möller, Berlin, Germany, B. Bokemeyer , Centre of
Gastroenterology, Minden, Minden, Germany, G. Moog , Centre of Gastroenterology,
Kassel, Kassel, Germany, U. Alshuth, Hoffmann-La Roche AG, Germany,
Grenzach-Wyhlen, Germany, D. Hüppe, Centre of Gastroenterology Herne, Herne,
Germany
Introduction
In an effort to measure the quality of treatment of patients
with chronic hepatitis C the Association of German independent
Gastroenterologists (bng) in cooperation with Hoffmann-La Roche, is conducting
a nationwide observational study that consists of documenting screening and
treatment data.
Methods
Between March 2003 and March 2005 data from >8000 patients
has been documented at > 500 centres. A total of 7156 patient screenings
have been completed and 2988 patients (41.8%) have been treated with
peginterferon alfa-2a (40KD) and ribavirin. Results of treatment, compliance
and side effects were recorded.
Results:
Demographic data are available for 2987 treated patients:
mean age 41,5 y, 61.7% male, naive/relapser/unknown 84.3/12 .4/4.5%
respectively, BMI 24.9 kg/m2, mean duration of infection: 11.4y, source of
infection (>1 answer possible): iv drug abuse 44.8%, transfusion 17.8%,
medical action 9.2%, contact to HCV infected person 81.%, tattoo/piercing 4.2%,
accident/injury 1.1% (multiple answers possible) and unknown 22.6%. The distribution of genotypes: GT1 59.6%
(1780), GT2 7.2% (214), GT3 29.8% (889), GT4-6 3.5% (104).
ALT: In 20.4% of the
patients ALT was normal (male max 50 U/l; female max. 35 U/L)
Concomitant diseases were reported in 51.1% of the
patients. Important diseases were abuse of
drugs/alcohol (31.7% of patients with concomitant disease), psychiatric
diseases (17.9%), cardiac diseases (13.2%), diabetes mellitus (7.5%), HIV/HCV
coinfection (7.0%), thrombocytopenia (3.9%) (multiple answers possible).
96% of patients were treated with a combination therapy. As
of March 2005 925/1164 patients with GT1 (79.5%) and 594/634 with GT2/3 (93.7%)
reached an Early Virological Response at week 12 ( EVR = ≥2-log10 drop in
HCV RNA or HCV RNA undetectable).
To date, 76.1% GT-1 (N=547/719) and 95.6% GT2/3 (N=538/563)
have achieved EOT Responses. Complete treatment data are available for 737
patients, who were treated according to consensus recommendations. Sustained
Virological Response (SVR) were achieved by 234/381 GT-1/4/5/6 (61.4%) and 302/357
GT2/3-patients (84.6%). To date 147 GT1/4/5/6
and 55 GT2/3 were nonresponders.
Discontinuations: A total of 443 (14.8%) patients have discontinued therapy:
40.5%, due to virological nonresponse 25.2% for poor tolerability, 13.8% were
lost to follow-up, 9.0% for personal reasons and 9.7% for lack of compliance
multiple answers possible).
The mean duration of absence from work was 11.4 days for
genotype 1/4/5/6-patients and 8.8 days
for genotype 2/3-patients.
Conclusion:
The results of this observational trial show that
peginterferon alfa-2a (40KD) and ribavirin therapy is effective and well
tolerated in patients with chronic hepatitis C in real world clinical practice.
When treated according to current guidelines, patients
achieved results similar to those achieved in controlled clinical trials. This
observational study contributes importantly to health care research of patients
with chronic hepatitis C.
Abstract ID: 64484
Category: JO7: HCV:
Treatment
VIRAL FACTORS INFLUENCE SVR IN PTS WITH HCV-RELATED BRIDGING FIBROSIS BUT NOT CIRRHOSIS.
A. Mangia,
GASTROENTEROLOGY DIVISION IRCCS, San Giovanni Rotondo, Italy, G. Scotto,
Infectious Diseases Division, Foggia, Italy, R. Cozzolongo, Gastroenterology
Division, Castellana Grotte, Italy, D. Bacca, Internal Medicine Division,
Casarano, Italy, N. Minerva, Internal Medicine Division, Canosa, Italy, V.
Carretta, Internal Medicine Division, Venosa, Italy, F. Spirito,
GASTROENTEROLOGY DIVISION IRCCS, San Giovanni Rotondo, Italy, A. Andriulli,
GASTROENTEROLOGY DIVISION IRCCS, San Giovanni Rotondo, Italy
BACKGROUND:
In patients with HCV-related bridging fibrosis or cirrhosis,
combination of RBV and PEG-IFN results in SVR rates which are 10-15% lower than
in those with milder fibrosis. AIM: To investigate whether viral- or disease
related factors, and adherence might account for these reduced rates.
PATIENTS AND METHODS:
Patients with either histologic or clinically apparent
advanced hepatic damage underwent treatment with PEG-IFN α 2a or α 2b
plus RBV (1000-1200 mg /daily) for standard duration depending on genotypes.
Mean age was 57.5 yrs (range 18-70), 67% were males. Genotypes 1 or 4 were
represented in 56% and viremia > 800.000 UI/ml in 60% of cases Platelets
counts, splenomegaly, oesophageal varices, albumin and cholesterol levels, and
prothrombin activity were recorded. Pts with ascites were excluded. Portal
Hypertension. was defined as the occurrence of oesophageal varices and/or
splenomegaly (>12 cm in size). Advanced disease was defined as presence of cirrhosis
with or without PH. Adherence to therapy was evaluated from the number of pts
with dose reduction of antiviral agents, and from the number of those withdrawn
from therapy for side effects .
RESULTS:
250 patients completed so far 24 weeks follow up. SVR was
achieved in 46% of pts overall (49% in F3 and in 44% in cirrhotic pts, P=0.44).
At univariate analysis factors associated with SVR in pts with bridging
fibrosis or cirrhosis are shown in the table. At multivariate analysis only
genotype independently predicted SVR in pts with bridging fibrosis (p= 0.001;
OR 3.9, 95% CI 2.1-7.1), whereas in advanced disease, platelets >110.000
μl (p=0.022, OR 2.4, 95% CI 2.1-5.1) and genotype (p=0.024, OR 2.4, 95% CI
1.1-5.3) were predictive of SVR.
CONCLUSIONS:
In pts with advanced disease high platelets counts and
favourable genotypes are predictors of SVR, whereas signs of portal
hypertension and suboptimal adherence are not.
Bridging fibrosis P value Advanced disease P value
Abstract ID: 64866
Category: JO7: HCV:
Treatment
RANDOMIZED, OPEN LABEL TRIAL COMPARING EFFICACY AND SAFETY OF PEGYLATED INTERFERON ALFA 2A VS ALFA 2B TREATMENT OF PATIENTS WITH CHRONIC HEPATITIS C INFECTED WITH NON 2/3 GENOTYPES – 12 WEEK VIROLOGICAL RESPONSE ANALYSIS.
H. Berak, Hospital of Infectious Diseases, Warsaw, Poland, A. Horban, Hospital of Infectious Diseases, Warsaw, Poland, M. Wasilewski, Hospital of Infectious Diseases, Warsaw, Poland, J. J. Stanczak, Hospital of infectious Diseases, Warsaw, Poland, A. Kolakowska- Rzadzka, Hospital of Infectious Diseases, Warsaw, Poland
Therapeutical efficiency of interferon alfa 2a (Pegasys, 40
KD) versus interferon alfa 2b (Pegintron, 12 KD) both in combination with
ribavirin was analyzed at 12 week of treatment.
PATIENTS:
237 patients (pts) with chronic hepatitis C were
consecutively divided into two groups. The A group (116 pts – 49%) was treated
with interferon alfa 2a; the B group (121 – 51%) with interferon alfa 2b. There
was no statistically significant difference in male/female ratios in both
groups (p>1,0). Genotyping score was similar in both group (101 pts - 87% vs
111 pts - 92% non 2 or 3 genotype, respectively). The highest percentage of patients in both groups were of
staging 1 – 48,2% and 42,6%, followed by staging 2 – 34,5% and 31,3%,
respectively.
METHODS:
Liver biopsies were analyzed according to the Knodell’s and
Scheuer’s scores. Patients’ age and body weight were determined and their
influence on treatment efficiency was analyzed. HCV genotypes were determined
with VERSANT-LIPA HCV II Test (INNOGENETICS); HCV RNA was determined with HCV
RNA ASSAY and viral load (VL) with CA HCV MONITOR TEST (both of ROCHE DIAGN
SYS.). The levels of ALT activity were determined with routine tests. Treatment
efficiency was estimated at 12 week. Early virologic response (ERV) was defined
as decrease of VL >2 log or undetectable HCV RNA.
RESULTS:
During therapy 3 pts from each group were excluded due to
side effects. 4 of them had genotype non 2/3 and they were included into the
group with treatment failure. Efficiency of therapy was analyzed in 208 pts
with genotype other than 2 or 3 – 98 pts in the A group and 110 pts in the B
group. The overall EVR rate was 79,3% (168/212). The EVR rate for the A group
was 85,1% (86/101) and 73,8% (82/111) in the B group. The difference is
statistically significant.
Therapeutical efficacy after 12 weeks of treatment
THERAPEUTICAL EFFICACY TOTAL GROUP A GROUP B
CONCLUSIONS:
Early therapeutical efficiency of interferon alfa 2a is significantly
higher comparing to those observed with interferon alfa 2b.
Abstract ID: 65337
Category: JO7: HCV:
Treatment
Economic evaluation of standard-therapy (ST) for chronic hepatitis C (CHC) with Peginterferon alfa-2a (40KD) (PegIFN 2a) plus Ribavirin versus Peginterferon alfa-2b (12KD) (PegIFN 2b) plus Ribavirin: Ready-to-use syringe (SYR) versus Injector (INJ).
H. D. Janisch,
Internistische Schwerpunktpraxen Erlangen, Erlangen, Germany, D. Hüppe, Centre
of Gastroenterology Herne, Herne, Germany, B. Möller , Centre of
Gastroenterology, Dr. Möller, Berlin, Germany, S. Mauss, Centre of
Gastroenterology and Hepatology, Düsseldorf, Germany, M. Rössle, Centre of
Gastroenterology Freiburg, Freiburg, Germany, S. Pape, Centre of
Gastroenterology Paderborn, Paderborn, S. Christensen, Independent General
Practice CIM, Münster, Germany, P. Hartmann, Centre of Gastroenterology Dr.
Hartmann, Münster, Germany
Background:
PegIFN 2a and PegIFN 2b are approved for therapy of CHC in
Europe. They have different pharmacological properties, which require different
formulations for administration.
Objective:
Evaluate and compare economic and handling aspects of
commercial formulations of PegIFN 2a (SYR) and PegIFN 2b (INJ) in the initial
phase of CHC-ST in routine medical practice in Germany.
Methods:
Patients were allocated to therapy with PegIFN 2a or PegIFN
2b at the investigators discretion. During the first 8 weeks of CHC-ST a
questionnaire was administered to physicians and nurses (at weeks 0, 2, 4, 8),
and to patients (at weeks 2, 4, 8). The questionnaire was concerned with time
required for patient education and drug administration, as well as documenting
difficulties encountered with the two formulations.
Results:
95 patients were recruited. As of May 2005 complete data are
available for 75 patients (37 SYR, 38 INJ). Mean total physician time consumed
in the 8 week study period, including time required for initial patient
education and drug administration (if necessary) plus additional patient
education (if necessary), was 3.9 and 7.8 minutes per patient for SYR and INJ,
respectively. A total of 13.0 and 17.6 minutes of nursing time was consumed by
the use of SYR and INJ, respectively. On the basis of 75 €/h for physician time
and 15 €/h for nursing time, total personnel costs per patient amounted to 8.2
€ for SYR and 14.1 € for INJ, respectively. Problems with self-administration
by patients occurred in 2.8% of SYR vs. 16.0% of INJ applications. The most
frequent problem was related to preparation of the injection. Additional
patient education for self-administration was necessary for 2.7% of SYR
patients vs. 23.7% of INJ patients. From the physicians’ perspective
self-administration led to problems in 14.3% of SYR applications and 45.8% of
INJ applications. Self-administration of SYR was considered to be user friendly
by 91.8% of patients, and of INJ by 71.3% of patients.
Conclusion:
In the initial phase of ST for CHC in routine medical
practice, therapy with PegIFN 2a using SYR is less time consuming and less cost
intensive with respect to handling than PegIFN 2b using INJ. The use of SYR is
associated with less handling problems than INJ, and self-administration of SYR
was judged to be more user friendly by the majority of physicians and patients.
Abstract ID: 65628
Category: JO7: HCV:
Treatment
Peripheral insulin resistance during the treatment of chronic C hepatitis with pegylated interferon plus ribavirin.
V. B. Mello, Federal
University of Bahia, Salvador, Brazil, R. Parana, Federal university of Bahia,
Salvador, Brazil, M. Simões, Federal University of Bahia, Salvador, Brazil, G.
R. Nuñez, Federal University of Bahia, Salvador, Brazil, T. R. Cruz, Federal
university of Bahia, Salvador, Brazil, N. Fabrizio, Federal university of
Bahia, Salvador, Brazil, M. Cruz, Federal university of Bahia, Salvador, Brazil
Patients with hepatitis C vírus (HCV) infection have a
highaer risk of developing type 2 diabetes mellitus. However, the mechanism of
this association and the role of antiviral treatment are still unclear. Our
study aimed to investigate the relationship between the use of peguilated
interferon and the development of insulin resistance on these patients.
Methods:
HOMA (homeostasis model assessment) was performed in 30 HCV-infected
patients just before and during the first 6 months of treatment with peguilated
interferon plus ribavirin. Antropometric parameters and glucose/cholesterol
profile were also monitored.
Results:
There was no change in HOMA after 6 months of treatment.
Glucose levels decreased but not significantly (p=0.059). Patients with higher
HOMA index after 6 months of treatment also had higher aminotransferases levels
(p=0.03), higher fat index on computed tomography (p=0.011), longer time of
exposure to the virus (p=0.021), and a positive smoking history when compared
to non-insulin resistant patients (p=0.045). There was no influence of fibrosis
stage on liver biopsy in the insulin resistance development, even though
insulin resistant patients had a greater necro-inflamatory index (p=0.02).
Conclusions:
There was no change in insulin resistance after six months of
treatment. Insulin resistence is related to abdominal fat and antropometric
parameters rather than antiviral treatment.
Abstract ID: 65944
Category: JO7: HCV:
Treatment
Week 4 Virological Response with Peginterferon Alfa-2a (40KD) (PEGASYS®) Plus Ribavirin (RBV, COPEGUS®) Portends a Sustained Virological Response (SVR) After 24 Weeks in Genotype 1 Chronic Hepatitis C Patients with Persistently ‘Normal’ ALT Activity.
N. Gitlin, Emory
University School of Medicine, Atlanta, GA, M. Manns, Medizinische Hochschule
Hannover, Hannover, Germany, K. Sherman, Univ. of Cincinnati College of
Medicine, Cincinnati, OH, T. Berg, Humboldt-Universitat zu Berlin Med Klinik,
Berlin, Germany, P. Pockros, The Scripps Clinic, La Jolla, CA, C. Hézode,
Hôpital Henri Mondor, Créteil, France, S. Roberts, The Alfred Hospital,
Melbourne, Australia, S. Zeuzem, Saarland University Hospital, Homburg, Germany
Introducation
SVR rates in HCV genotype 1 patients with persistently
‘normal’ ALT activity were significantly higher after 48 than 24 wks of
treatment with peginterferon alfa-2a (40KD) (PEGASYS®) plus RBV (COPEGUS®) (40%
vs 13%, p<0.001; Zeuzem et al. Gastroenterology 2004). We evaluated whether
a rapid virological response (RVR) at week 4, defined as undetectable HCV RNA
(<50 IU/mL) portended an SVR in patients treated for 24 wks in this study.
Methods
Treatment-naïve patients with persistently ‘normal’ ALT
activity and quantifiable HCV RNA (>600 IU/mL) were randomized to 24 or 48
wks of treatment with peginterferon alfa-2a (40KD) 180 μg/wk + RBV 800
mg/d (the trial was initiated before the optimal regimen for genotype 1 was
known: 48wks with an RBV dose of 1000/1200 mg/d). Multiple logistic regression
(MLR) was used to identify baseline factors (sex, age, weight, HCV RNA level,
ALT, histological diagnosis, fibrosis score and region) predictive of an SVR in
patients treated for 24 wks.
Results
144 genotype 1 patients were randomized to 24 wks of
treatment, 140 had a wk 4 virological test result and 130 completed therapy.
Patients with an RVR had higher end of-treatment (EOT) virological response and
SVR rates (table) and lower relapse rates between EOT and end of follow-up (25
vs 93%) than those without an RVR. MLR analysis revealed baseline HCV RNA level
to be the only significant predictor of SVR in patients treated for 24 wks.
Those with baseline HCV RNA ≤ 200,000 IU/mL (n=21) were significantly
more likely to achieve an SVR than those with serum HCV RNA >200,000 IU/mL
(n=123) [odds ratio (OR) 4.6; 95%CI 1.6-13.7, p=0.0057]. When the week 4 test
result was included in the model, only SVR was a significant predictor of SVR
[OR 39.2; 95%CI 10.9-144.8; p<.0001).
Conclusion
- The
proportion of genotype 1 patients who achieved an RVR with peginterferon
alfa-2a (40KD) (PEGASYS) plus ribavirin (COPEGUS) was similar, regardless
of ALT activity, in multinational, randomized, phase III trials. Overall, 39/276 patients (14%) with persistently
‘normal’ ALT and 181/1024 patients (18%) with elevated ALT achieved an
RVR.
- An
RVR at week 4 is highly significant predictor of an SVR after 24 weeks’
treatment.
- Nearly
three quarters (12/17 (71%)) of genotype 1 patients with an RVR achieved an
SVR after 24 weeks with peginterferon alfa-2a (40KD) plus ribavirin
therapy.
- Low
baseline RNA was a significant predictor of SVR in genotype 1 patients
treated for 24 weeks with peginterferon alfa -2a (40KD) plus
ribavirin. However, the week 4 test
result was included in the analysis, RVR was the only significant
predictive factor for an SVR.
- Although
virological relapse rates were higher in patients treated for 24 or 48
weeks without an RVR, relapse rates were lower in patients treated for 48
versus 24 weeks. As such, further
study is required before this criterion can be used as a guide to
treatment duration in patients with HCV genotype 1 and persistently
‘normal’ levels.
Abstract ID: 66069
Category: JO7: HCV:
Treatment
Specific mechanisms of HCV-3 on hypocholesterolemia. Long-term effect of sustained virological response.
C. M. Fernandez-Rodriguez, Fundacion Hospital Alcorcon, Madrid, P. Lopez
Serrano, Fundacion Hospital Alcorcon, Madrid, Spain, M. Gutierrez Garcia,
Fundacion Hospital Alcorcon, Madrid, Spain, J. Lledó Navarro, Fundacion
Hospital Alcorcon, Madrid, Spain, M. Nevado, Fundacion Hospital Alcorcon,
Madrid, Spain
Background:
Genotype-3 of hepatitis-C virus has been associated with
hypocholesterolemia and liver steatosis. Reversal of these changes in patients
with sustained virological response (SVR) has been reported. Yet, the long-term
effect of this response is not known.
Objectives and methods:
To define baseline differences of serum cholesterol, its
relationship with liver steatosis in patients infected with genotype 3 and in
those infected with genotype 1 and its long-term time-course with treatment. A
cohort of 215 patients with chronic hepatitis C referred to our unit was
studied (genotype 1, n: 158; genotype 2, n: 4; genotypes 4 and 5, n: 12 and
genotype 3, n: 41) and 25 patients with chronic hepatitis B. Covariates were
age, body mass index (BMI), gender, alcohol intake, serum lipids, glycaemia,
serum ALT, AST, GGT, grade and stage (metavir and scheuer), degree of liver
steatosis and SVR.
Results:
Patients infected by genotype 3 had age-adjusted
hypocholesterolemia and more frequent hepatic steatosis (p<0.001). Steatosis
inversely correlated with serum cholesterol (p<0.01). In patients with
genotype-3 and SVR, serum cholesterol raised from 140 mg/dl (CI 120-151) to 185
mg/dl (CI 171-199) twelve months after the end of treatment (p: 0.0001). By
contrast, serum cholesterol did not change in non-responders with genotype-3 or
in patients with genotype 1 regardless of virological response. Once excluded
patients with genotype-3, there were not differences regarding serum
cholesterol between patients with HCV and those with HBV.
Conclusions:
Besides causing hepatic steatosis, genotype-3 specifically
decreases serum cholesterol. This interference with the metabolic lipid pathway
reverses with SVR and it is sustained on a long-term basis.
Abstract ID: 66208
Category: JO7: HCV:
Treatment
Persistence with Hepatitis C Therapy in African Americans and Patients with Depression in the Department of Veterans Affairs (VA).
F. Cunningham, Hines VA
Hospital, Hines, IL, A. Lee, Boston University School of Public Health, Boston,
MA, S. Usman Iqbal, Boston University School of Public Health, Boston, MA, D.
R. Miller, Boston University School of Public Health, Boston, MA, A. W. Law,
Roche Laboratories, Nutley, NJ, L. Kazis, Boston University School of Public
Health, Boston, MA
Introduction
Certain populations infected with Hepatitis C virus (HCV)
have been reported to have a decreased
response to treatment. The African American (AA) population and those patients
suffering from depression have been identified as two groups with a lower response
to Hepatitis C treatment.
The specific reasons for a decrease in response have not been
clearly identified. Moreover, persistence with prescribed HCV therapy has not
been adequately studied in these populations. The goal of this study is to
evaluate persistence in the AA and depressed patients undergoing treatment for
HCV in the Department of Veterans Affairs.
Objective
To evaluate and compare treatment persistence in African
American patients infected with HCV who received combination therapy with
either peginterferon alfa-2a with ribavirin (peg-INF alpha–2a/Rib) or
peginterferon alfa-2b with ribavirin (peg-INF alpha-2b/Rib)
To evaluate and compare treatment persistence in patients
diagnosed with depression infected with HCV who received combination therapy
with either peginterferon alfa-2a with ribavirin (peg-INF alpha–2a/Rib) or
peginterferon alfa-2b with ribavirin (peg-INF alpha-2b/Rib)
Study Design
A retrospective inception cohort claims analysis on treatment
naïve patients diagnosed with HCV.
Data Sources
The pharmacy databases (PBM v 3.0), the National Patient
Files, and the Beneficiary Identification and Record Location (BIRLS) files of
the Department of Veterans Affairs (VA) were utilized for the study.
Study Period
The study population included patients who had a diagnosis
for hepatitis C virus between October 1, 2002 and September 30, 2004 (Fiscal
Years 2003 - 2004) and a prescription for combination peginterferon (peg-IFN
alpha-2a/Rib, PEG-IFN alpha-2b/Rib) during the same time period. The index date
was defined as the date of the first claim of the specified drugs. The period
of October 2000 to September 2002 (or 24 months prior to receiving treatment)
was used to assess patients for comorbid conditions listed under the exclusion
criteria.
Defining Variables
Persistence: A patient with a no-fill period of
more than 60 days after a prescription of the study drugs was termed as
discontinued. Persistence time was defined as the period from the date of first
prescription to the date of discontinuation for the therapy initially
prescribed.
Data Management and
Analyses Plan:
Patient demographics were abstracted and analyzed from the VA
administrative databases. Persistence rates were calculated for each of the two
treatment groups using the Kaplan-Meier method.
Likelihood ratio test of equality between the two treatment groups was
performed to detect any differences in persistence rates. Key variables for
stratification included (1) race - white and African American and, (2) those
diagnosed with depression.
Inclusion criteria
· Male and female
veterans > 18 years of age
· At least one pharmacy
claim for a 30-day supply of peginterferon alfa-2a, peginterferon alfa-2a/Rib,
peginterferon alfa-2b, or peginterferon alfa-2b/Rib
· An inpatient discharge
diagnosis or at least 1 outpatient diagnosis for HCV in the 12 months prior to
the index date.
· Treatment-naïve as
defined by no HCV treatment in the 12 months prior to the index date.
· At least one clinic
visit or inpatient diagnosis in the subsequent twelve months following the index
date to assure contact with the VA system.
Exclusion Criteria
· Presence of ICD-9 codes
for any of the following comorbidities during the 24 months prior to the index
date: HIV, Hepatitis B, Thrombocytopenia, Neutropenia, Anemia, Hemorrhage or
active bleeding, Chronic renal failure, Bone marrow disorder, Cancer.
· Patients with pharmacy
claim(s) for a 60-day or 90-day supply of peginterferon alfa-2a, peginterferon
alfa-2a/Rib, peginterferon alfa-2b, or peginterferon alfa-2b/Rib
Results
The study sample consisted of 816 (27%) AA patients and 1,984
(35%) patients with a history of depression.
Persistence with peginterferon alfa-2a/Rib was not significantly
different (p=0.28) between AA and whites. The median duration of therapy was
5.3 months for whites vs. 4.7 months for blacks in the peginterferon
alphs-2a/Rib group. Persistence was
significantly lower in AA compared to whites in the peginterferon alfa-2b/Rib
group (p=0.0063). The median duration of therapy was 4.6 months for whites vs.
3.6 months for AA in the peginterferon alpha-2b/Rib group. There was no
difference in persistence with either therapy
CONCLUSION
· There was no difference
in treatment in duration of therapy or persistence between AA and whites in the
pegylated interferon alfa-2A/Rib treatment group.