Monday Poster Sessions,
Topic: HCV
Epidemiology – General
M. Lee; H. Yang; C. Liu; S. You; P. Chen; C. Chen
Background and aims:
Chronic hepatitis C virus (HCV) infection is an important
risk predictor of hepatocellular carcinoma (HCC). But the cumulative HCC
incidence associated with chronic HCV infection has rarely been examined by
community-based long-term follow-up studies. This prospective study aimed to
evaluate the impacts of HCV on HCC in
Methods:
A total of 19,565 residents who were HBsAg-seronegative and
free of liver cirrhosis or HCC at entry were enrolled during 1991 to 1992.
There were 1,041 anti-HCV-seropositives and 18,524 anti-HCV-seronegatives. They
were followed until
Results:
During the follow-up of 246,154 person-years, the cumulative
HCC incidence per 100,000 person-years was 26 for anti-HCV-seronegative
participants, 290 for anti-HCV-seropositives with undetectable HCV RNA, 464 for
anti-HCV- seropositives with detectable genotype 1 HCV RNA, and 370 for
anti-HCV- seropositives with detectable genotype non-1 HCV RNA. Compared with
anti-HCV- seronegative participants as the referent group, the HRadj
(95% CI) was 8.0 (4.3-14.7) for anti-HCV-seropositives with undetectable HCV
RNA, 6.6 (3.9-11.2) for anti-HCV-seropositives with detectable genotype 1 HCV
RNA, and 6.2 (3.3-11.7) for anti-HCV-seropositives with detectable genotype
non-1 HCV RNA after adjustment for age, gender, cigarette smoking and serum ALT
level at study entry. The HRadj (95% CI) was 2.7 (1.7-4.1) and 7.6
(4.4-13.1), respectively, for serum ALT levels of 16-45 and >45 IU/L
compared with ALT level <15 IU/L. Cigarette smoking was also associated with
an increased HCC risk with an HRadj (95%
CI) of 1.7 (1.0-2.8). In the stratification analyses, the age-gender-adjusted
HRadj (95% CI) for the anti-HCV- seropositives with undetectable HCV
RNA, anti-HCV-seropositives with detectable genotype 1 HCV RNA, and anti-HCV-seropositives
with detectable genotype non-1 HCV RNA was 25.7 (7.3-90.9), 10.7 (3.3-34.6) and
11.3 (3.3-39.7), respectively, for those with ALT levels at entry >45 IU/L.
The corresponding figures were 5.2 (2.2-12.0), 9.8 (5.3-18.2), and 7.5 (3.2-17.5)
for those with ALT levels at entry < 45 IU/L.
Conclusion:
HCV infection, elevated serum ALT levels, and cigarette
smoking are important HCC risk predictors for HBsAg-seronegatives in
Topic: HCV
Epidemiology – IDU
J. Grebely; J. D. Raffa; C. Lai; M. Krajden; B.
Fischer; T. Kerr; M. W. Tyndall
Purpose:
To estimate HCV treatment uptake in a
large community-based inner city cohort in
Methods:
CHASE is a cohort study of inner city residents recruited
from January 2003 to June 2004. HIV and HCV status were determined through
linkage with provincial databases. Treatment information was derived from the
British Columbia Ministry of Health Pharmacare database (January 2000 to
December 2004), which contains information on all HCV treatment prescriptions
in the province. The incidence of HCV infection and the rate of HCV treatment
uptake were calculated, expressed in terms of person-years of observation and
compared over the follow-up period.
Results:
As of December 2004, among 3,553 subjects enrolled into the cohort,
HCV antibody testing was performed in 2,117 and the HCV seroprevalence was
64.3% (n=1,361). In total, between January 2000 and December 2004, 15 HCV
antibody positive subjects initiated treatment for HCV (1.1%), accounting for a
total of 5420 person years of follow-up, yielding an overall treatment uptake
of 0.3 cases per 100 person years (95% CI, 0.1-0.4). Overall, only 3 of 15
(0.2%) HCV antibody positive subjects achieved an SVR. During the same period,
91 HCV seroconversions were observed among a total of 1285 person years of
follow-up, yielding an overall incidence of 7.1 cases per 100 person years (95%
CI, 5.6-8.5). The incidence of HCV infection among recent injection drug users
was 23.1 cases per 100 person years (95% CI, 17.5-28.5).
Conclusions:
We have documented extremely low rates of HCV treatment
initiation and limited effectiveness of antiviral treatment for HCV, despite a
high prevalence and incidence of infection in a large community-based cohort of
inner city residents in
Topic: HCV
Epidemiology – HIV/HCV Coinfection
E. Rosenthal; D. Salmon; C. Lewden; F. Bonnet; T. May;
P. Morlat; M. François; C. Burty; E. Jougla; D. Costagliola; G. Chêne; P.
Cacoub
Objective:
To determine mortality due to end-stage liver disease(ESLD) and the profile of patients who died from ESLD
in a nationwide population of HIV-infected patients and the evolution over a
10-years period.
Design and methods:
All departments of internal medicine and infectious diseases
from the GERMIVIC Study Group prospectively recorded all deaths in HIV-infected
patients during 2005. Fifty six departments, following around 35,000
HIV-infected patients, participated in the study. Results were compared with
those of previous surveys conducted using similar methodology in 1995, 1997,
2001 and 2003.
Results:
Among 364 deaths documented during 2005, 142 (39.0%) were
related to AIDS, 64 (17.6%) to ESLD, 55 (15.1%) to cancers neither related to
HIV nor hepatitis viruses, 20 (5.5%) to cardiovascular diseases and 83 (22.8%)
to other causes. Mortality due to ESLD represented 28.8% of non AIDS-related
deaths. Patients dying from ESLD had chronic hepatitis due to virus C in 79.6%
of cases and 46.6% of these patients had high alcohol consumption (> 30g/day)(table 1). In the Germivic survey, the proportion of
ESLD-deaths has increased: 5% in 1995, 6.6% in 1997, 14.3% in 2001, 12.6% in
2003 and 17.6% in 2005, p<0.01. The proportion of hepatocellular carcinoma
as a cause of death increased over this 10-years period (4.7% in 1995 vs 31.2%
in 2005, p<0.01). Treatment of hepatitis C in patients who died from ESLD was
more frequent in 2005 (37.5%) than in 1995 (19.0%), p<0.01.
Conclusions:
In HIV-HCV coinfected patients, the proportion of HCV-ESLD is
still increasing and it constitutes a leading cause of mortality in this
population.
Table 1.Characteristics of patients who died from ESLD in 1995, 1997, 2001, 2003 and 2005
|
|
1995 n = 21 |
1997 n = 36 |
2001 n = 38 |
2003 n = 27 |
2005 n = 64 |
|
Sex, male, no (%) |
15 (71.4) |
30 (83.3) |
30 (78.9) |
22 (81) |
53 (83) |
|
Mean age, y (range) |
41 (26-66) |
42 (31-62) |
42 (32-69) |
42 (36-54) |
45 (35-68) |
|
Injection drug use, no (%) |
6 (28.5) |
14 (38) |
29 (76.3) |
26/26 (100) |
39/63 (61.9) |
|
Alcohol consumption > 30g/day, no (%) |
6 (28.5) |
16 (44.4) |
19 (50) |
16 (59.2) |
28/60 (46.6) |
|
HBsAg positive, no (%) |
8 (38.1) |
15 (41.7) |
8 (21.1) |
2 (7.4) |
17 (26.5) |
|
HCC, no (%) |
1 (4.7) |
4 (11.1) |
9 (25) |
4 (14.8) |
20 (31.2) |
|
Anti-HCV treatment, no (%) |
4 (19) |
3 (8.3) |
10 (26.3) |
12 (44.4) |
24 (37.5) |
|
CD4 count (cells/mm3), median (IQR) |
113 (27-257) |
131 (46-306 |
158 (72-303) |
132 (66-350) |
239 (110-355) |
|
HAART, no (%) |
0 |
15 (41.6) |
28 (73.6) |
23 (85) |
58 (90.6) |
ESLD, end-stage liver
disease; HCV, hepatitis C virus; HCC, hepatocellular carcinoma; HAART, highly
active antiretroviral therapy
Topic: HCV
Epidemiology – Tattoos
S. Dhalla; C. T. Tenner; A. Aytaman; N. B. Shukla; G.
Villanueva; G. Punla; C. Patterson; J. Comas; E. J. Bini
Background:
Although injection drug use and blood transfusions prior to
1992 are well-accepted risk factors for hepatitis C virus (HCV) infection, the
evidence for tattoos as a risk factor for HCV is conflicting. Furthermore,
several prior studies that have evaluated tattoos as a risk factor for HCV
infection were potentially confounded by injection drug use. The aim of this
study was to determine the association between tattoos and HCV infection in a
large population of patients without traditional risk factors for HCV
infection.
Methods:
Patients with chronic HCV infection (HCV RNA positive) and
controls (HCV antibody negative) completed a detailed questionnaire at the time
of their scheduled visit to the outpatient primary care or GI clinic at 3 study
sites. Data collected included patient demographics and information on HCV risk
factors.
Results:
A total of 3,871 patients were enrolled, including 1,930 with
chronic HCV infection and 1,941 HCV negative controls. There were no
differences in the mean age (55.2 ± 9.0 vs. 55.6 ± 11.3 years, p = 0.34) or the
proportion who were male (80.3% vs. 81.4%, p = 0.39) between HCV-infected
patients and controls. However, HCV positive patients were more likely to be
racial/ethnic minorities (78.5% vs. 56.5%, p <0.001). As expected, injection
drug use (65.9% vs. 17.8%, p < 0.001) and blood transfusions prior to 1992
(22.3% vs. 11.1%, p <0.001) were more common in HCV-infected patients than
in control subjects. Patients with HCV infection were significantly more likely
to have had one or more tattoos (35.2% vs. 12.5%; OR = 3.81; 95% CI, 3.24 –
4.49; p <0.001) and this remained highly significant after adjustment for
age, sex, and race/ethnicity (OR = 4.57; 95% CI, 3.83 – 5.45; p <0.001). After excluding all patients with a history of ever injecting drugs
and those who have had a blood transfusion prior to 1992, a total of 1,887
subjects remained for analysis (466 HCV positive and 1,421 controls).
Among these 1,887 patients without traditional risk factors for HCV infection,
we found that HCV positive patients were still significantly more likely to
have a history of tattoos (34.1% vs. 11.9%; OR = 3.84; 95% CI, 2.99 – 4.93; p
<0.001) and this remained highly statistically significant after adjustment
for age, sex, and race/ethnicity (OR = 4.47; 95% CI, 3.42 – 5.83; p <0.001).
Conclusions:
Tattoos are strongly associated with HCV infection, even
among those without traditional HCV risk factors such as injection drug use and
blood transfusions. All patients with tattoos should be offered HCV testing.
Topic: HCV
Epidemiology – General
M. Danta; T. van de Laar; D. Brown; O. Pybus; S.
Bhagani; M. Vogel; S. Neifer; A. Baumgarten; H. Gotz; J. Rockstoh; S. Bruisten;
G. M. Dusheiko
Introduction:
Since 2000, there has been a reported rise in permucosal HCV
transmission among European HIV-positive MSM related to high-risk sexual
behaviours. We conducted a phylogenetic study to investigate the presence of a
HCV transmission network among European MSM.
Methods:
HIV-positive MSM diagnosed with acute HCV (n=178) in
Results:
NS5B sequences were obtained from 154/178 (87%) of cases;
Conclusion:
This phylogenetic analysis reveals a large HCV transmission
network among HIV-positive MSM in
Topic: HCV
Epidemiology – HIV/HCV Coinfection
A. Monto; S. Currie; L. M. Dove; D. Tracy; S. George;
A. Myers; J. C. Ryan; T. L. Wright
Background:
HIV coinfection may accelerate the complications of hepatitis
C virus (HCV) infection. Much of this perception, however, has been based on
retrospective case series or short-term prospective follow-up.
Aim:
To explore mortality and liver-related complications in a
prospective cohort of American inner-city injection drug users,
followed at an urban county and a veterans hospital, who have chronic HCV.
Methods:
350 patients were enrolled beginning in 1997 and have been
followed for a mean of 4.8 years. 176 patients (49.7%)are
chronically coinfected with HIV and hepatitis C, and 174 patients had chronic
HCV infection alone. Causes of death were determined by the investigators, and
were attributed to HIV, end-stage liver disease (ESLD) or drugs only when this
was unequivocal. Cirrhosis was defined by histology or overt clinical or
radiological evidence of cirrhosis.
Results:
Overall, 48 HIV-HCV coinfected and 34 HCV monoinfected
patients died during follow-up, but coinfected patients did not have
statistically-significantly increased death than the group overall (O.R. 1.54,
95% CI 0.94-2.54, p=0.09), data shown in Table. Similar proportions of
coinfected patients were also found to develop cirrhosis, 29 (16%), as compared
to monoinfected patients, 31 (18%, t-test p=NS). HAART was not protective
against death in coinfected patients: 34/48 (71%) of coinfected patients who
died had regularly received HAART, 29% had not (t-test p=NS).
Conclusions:
HIV-HCV coinfected and HCV monoinfected patients, when
followed prospectively, have similar rates of death or cirrhosis. End-stage
liver disease and HIV are competing causes of death in coinfected patients.
Reported high rates of ESLD-associated death in coinfected patients alive today
should be interpreted with caution, and compared to those in similar groups of
HCV monoinfected patients. As the HAART era continues, morbidity and mortality
in HIV-positive patients may approach that of their HIV-negative counterparts.
Table 1. Clinical Outcomes
|
HIV-HCV |
Deaths |
Overall |
48 (27%) |
|
|
|
HIV-Assoc |
7 (4%) |
|
|
|
Other |
18 (10%) |
|
|
|
ESLD-Assoc |
12(7%) |
|
|
|
Drug-related |
0 (0%) |
|
|
|
Unknown |
11 (6%) |
|
|
Cirrhosis |
|
29 (16%) |
|
HCV |
Deaths |
Overall |
34 (19%) |
|
|
|
Other |
16 (9%) |
|
|
|
ESLD-Assoc |
6 (3%) |
|
|
|
Drug-related |
1 (1%) |
|
|
|
Unknown |
11 (6%) |
|
|
Cirrhosis |
|
31 (18%) |
Topic:
Treatment – Pegasys
LB1.
Prolonged Antiviral Therapy With
Peginterferon to Prevent Complications of Advanced Liver Disease Associated
With Hepatitis C: Results of the Hepatitis C Antiviral Long-term Treatment
against Cirrhosis (HALT-C) Trial
A. M. Di Bisceglie; M. L. Shiffman; G. T. Everson; K.
L. Lindsay; J. E. Everhart; E. C. Wright; W. M. Lee; A. S. Lok; H. Bonkovsky;
T. R. Morgan; J. L. Dienstag; M. Ghany; C. Morishima; K. K. Snow
Background:
Chronic hepatitis C may lead to progressive liver disease
with cirrhosis, liver failure, hepatocellular
carcinoma (HCC) and death. Not all pts treated with peginterferon and ribavirin
achieve a sustained virologic response (SVR); whether long-term antiviral
therapy can prevent progressive liver disease in those who do not achieve SVR
remains uncertain.
Aims:
To determine if long-term maintenance therapy with
peginterferon prevents progressive liver disease resulting from hepatitis C.
Methods:
We conducted a randomized controlled trial of peginterferon
alfa-2a (90 mcg per week) for 3.5 years vs. no treatment in pts with chronic
hepatitis C and advanced fibrosis who were nonresponders to prior therapy with
peginterferon and ribavirin. Subjects eligible for enrollment had chronic
hepatitis C with an Ishak fibrosis score of ≧3 on liver biopsy, a
Child-Turcotte-Pugh (CTP) score of ≦6, no history of ascites,
encephalopathy or bleeding varices, and no other identifiable cause of liver
disease. Participants were stratified according to their stage of fibrosis –
Ishak stage 3 or 4 (622 with fibrosis) vs. 5 or 6 (428 with cirrhosis). Pts
were seen at 3 month intervals, underwent liver biopsy at 1.5 and 3.5 years
after randomization, and were monitored for the following outcomes: death, HCC,
hepatic decompensation (variceal hemorrhage, ascites, spontaneous bacterial
peritonitis, encephalopathy or a CTP score of ≧7), and, for those with pre-cirrhotic
fibrosis at baseline, an increase in fibrosis score of ≧2
points.
Results:
1050 pts were randomized (517 treatment, 533 control). By the end of the study, 34.1% of the treatment
and 33.8% of the control group had experienced an outcome (hazard ratio=1.01;
95% CI=0.81-1.26; p=0.91). Although mean serum ALT and HCV RNA levels decreased
significantly with treatment (both p<0.0001), as did necroinflammatory
changes on liver biopsy (p<0.0001), no significant difference was observed
in rates of any of the primary outcomes between groups (Table). The rate of
serious adverse events was similar in both groups (284 events among 175 treated
and 283 events among 155 control pts). Among treated pts, 17% stopped
peginterferon by year 1.5 and 30% by year 3.5.
Summary and
Conclusions:
Long-term therapy with peginterferon did not reduce the rate
of disease progression. These findings do not support maintenance therapy with
peginterferon in patients with chronic hepatitis C and advanced hepatic
fibrosis who are nonresponders to a course of peginterferon/ribavirin therapy.
|
|
Death (%) |
Decompensation (%) |
HCC (%) |
Increase in fibrosis (%) |
|
Treatment (n=517) |
6.6 |
14.3 |
2.8 |
28.2 |
|
Control (n=533) |
4.6 |
13.2 |
3.2 |
31.9 |
Topic:
HIV/HCV Coinfection
A. C. Tuyama; F. Hong; A. D. Schecter; A. Mosoian; B.
K. Chen; P. Chen; M. E. Klotman; M. B. Bansal
Introduction:
Patients co-infected with HIV/HCV develop more rapid fibrosis
than patients mono-infected with HCV. Fibrosis progression correlates with HIV
viremia suggesting a direct role of HIV in liver fibrogenesis. CCR5 and CXCR4
are the 2 major co-receptors required for HIV entry into cells. CCR5 has been
reported on hepatic stellate cells (HSCs) and we have recently demonstrated the
expression of CXCR4 on HSCs (Hong,#1400; AASLD 2007).
Gp120 is the envelope protein for HIV and can activate cells independent of
direct infection.
Aim:
The aim(s) of this study are to 1) Examine whether HIV
enters HSCs and actively replicates 2) Characterize the impact of HIV and gp120
on HSC biology. First the capacity of HIV IIIB (CXCR4-tropic or X4) and HIV-Bal
(CCR5-tropic or R5) to infect HSCs was assessed by ELISA for supernatant p24, a
marker for virus being released from the cells. LX2 cells, a human HSC line,
were infected and washed to remove unbound virus. Significant concentrations of
p24 (>2ng/ml) were detected on all days examined (up to 7 days). Since X4
viruses predominate later in the course of HIV disease coincident with chronic
liver disease in patients with HCV/HIV, we examined whether HIV IIIB infects
primary human HSCs (passage #3-4) and replicates using p24 assay and qRT-PCR
for unspliced(US) and multiply-spliced(MS) HIV-1 RNA.
The detection of p24 (>8ng/ml)associated with
intracellular US and MS HIV suggests active replication (confirmed by
sequencing of MS HIV-1). The ability of HIV to infect HSCs was confirmed by
challenging the cells with a recombinant HIV expressing GFP in place of the
early gene nef. The finding of GFP-positive cells indicates HIV entry and early
gene expression. As HIV infection may be either CD4-dependent or -independent,
CD4 expression by HSCs was documented by immunofluorescence. CD4-blocking
experiments revealed that HIV IIIB entry into HSCs was CD4-independent. HIV
infection promoted HSC activation, since qRT-PCR demonstrated a 1.6-fold
(p<0.0001) and 1.5-fold (p<0.0001) increase in collagen α1(I) and α-SMA mRNA levels,
respectively. Furthermore, incubation with either monomeric gp120(X4) or AT-2
treated X4(oligomeric gp120) for 1-24 hrs resulted in a 2.1-fold (p<0.007)
and 1.4-fold (P<0.004) increase in collagen α1(I)
mRNA levels, respectively.
Conclusions:
HIV enters and actively replicates within HSCs independent of
CD4. Both viral entry as well as exposure of cells to viral envelope
glycoproteins can promote activation and collagen induction in HSCs. These
results suggest that direct infection or Env-mediated activation of HSCs may
contribute to rapid development of fibrosis in patients co-infected with
HIV/HCV.
Topic:
Treatment – Pegasys
D. M. Jensen; B. Freilich; P. Andreone; A.
DiBisceglie; C. E. Brandão-Mello; K. Reddy; A. Craxi; A. Martín; G. Teuber; D.
Messinger; G. Hooper; M. Popescu; P. Marcellin
Introduction:
Treatment options are limited for patients (pts) who are
previous non-responders to Peg-IFN/RBV. Intensified treatment with higher
fixed-dose induction of Peg-IFN and/or longer treatment duration may increase
SVR rates in these pts. REPEAT compared both strategies in prior non-responders
to ≥12 wks of Peg-IFN α-2b (12KD, PegIntron®)/RBV.
Methods:
Eligible pts were randomized (2:1:1:2) to 1 of 4 regimens,
Arms A and B Peg-IFN α-2a (40KD; PEGASYS®) 360 μg/wk for
12 wks then 180 μg/wk for a further 60 or 36 wks, respectively; Arms C and
D Peg-IFN α-2a (40KD) 180 μg/wk for 72 or 48 wks, respectively. All
pts received RBV (COPEGUS®; 1000/1200 mg/day). The primary endpoint
was SVR (HCV RNA <50 IU/mL 24 weeks post-therapy).
Results:
A total of 942 pts were randomized and dosed. Key baseline
(BL) characteristics were similar across arms. For the protocol-defined primary
analysis the SVR rate was higher for the 72-wk induction arm (Arm A: 16%)
compared to the 48-wk non-induction arm (Arm D: 9%) [p=0.006, OR 2.0 (95% CI
1.21-3.31)]. Furthermore, SVR was higher for pooled 72-wk arms vs pooled 48-wk
arms [p=0.0006, OR 2.22 (95% CI 1.40-3.52)]. Tolerability of induction and
non-induction regimens of Peg-IFN α-2a were
similar and overall the rate/type of AEs/SAEs were similar across arms.
Discontinuation rates due to safety were lower for the 48-wks arms.
Conclusion:
In these difficult to cure pts with prior documented
non-response to Peg-IFN α-2b/RBV, re-treatment with fixed-dose induction and
longer duration with Peg-IFN α-2a (40KD)/RBV provided the highest SVR
rates and the lowest relapse rates. Re-treatment with 72-wks of Peg-IFN
α-2a provided higher SVR rates than 48-wks, irrespective of induction.
|
|
Peg-IFN α-2a (40KD) plus
RBV 1000/1200 mg/day |
|||
|
|
A (n=317) 360/180 μg/wk (72 wk) |
B (n=156) 360/180 μg/wk (48 wk) |
C (n=156) 180 μg/wk (72 wk) |
D (n=313) 180 μg/wk (48 wk) |
|
Males (%) |
64% |
60% |
69% |
68% |
|
Mean ± SD Age (yrs) |
48.1 ± 8.7 |
48.8 ± 9.9 |
49.4 ± 8.5 |
48.5 ± 9.0 |
|
Caucasian (%) |
88% |
90% |
88% |
90% |
|
Mean ± SD Weight (kg) |
81.5 ± 18.2 |
81.1 ± 16.8 |
81.2 ± 16.0 |
80.9 ± 16.9 |
|
Genotype 1 (%) |
91% |
91% |
91% |
91% |
|
Mean ± SD BL HCV RNA (x 106 IU/mL) |
5.4 ± 6.4 |
5.3 ± 7.1 |
4.9 ± 5.1 |
4.9 ± 6.0 |
|
Cirrhosis (%) |
25% |
29% |
30% |
28% |
|
EoT response rate, n (%) |
99 (31%) |
52 (33%) |
48 (31%) |
88 (28%) |
|
SVR rate, n/N
(%) Overall BL VL ≤800
000 BL VL >800 000 |
52/317 (16%) 22/61 (36%) 29/244 (12%) |
11/156 (7%)
2/22 (9%) 9/130 (7%) |
22/156 (14%) 5/25 (20%) 17/128 (13%) |
27/313 (9%) 9/62 (15%) 16/233 (7%) |
|
Relapse Rate, n/N* (%) |
48/92 (52%) |
38/49 (78%) |
30/47 (64%) |
55/81 (68%) |
|
Premature d/c for safety, n (%) |
37 (12%) |
7 (4%) |
18 (12%) |
20 (6%) |
|
Pts with
SAEs, n (%)
Overall Hematological |
33 (10%) 5 (2%) |
14 (9%) - |
28 (18%) 3 (2%) |
33 (11%) 6 (2%) |
|
Peg-IFN α-2a dose modifications, n (%) |
72 (23%) |
41 (26%) |
36 (23%) |
57 (18%) |
*N=Pts
with negative EoT HCV RNA and ≥1 post-EoT HCV RNA value
Topic:
Experimental Treatment – VX-950
80. PROVE2:
Phase II Study of VX950 (TELAPREVIR) in Combination with Peginterferon ALFA2A
With or Without Ribavirin in Subjects With Chronic
Hepatitis C, First Interim Analysis
C. Hezode; P. Ferenci; G. M. Dusheiko; S. Pol; T.
Goeser; J. Bronowicki; S. Gharakhanian; D. Devonish; R. Kauffman; J. Alam; J.
Pawlotsky; S. Zeuzem
Background:
PROVE2, study VX05-950-104EU is a randomized,
placebo-controlled phase II study of telaprevir (TVR), in combination with pegylated
interferon alfa2a (Peg-IFN) and ribavirin (RBV), in treatment naïve subjects
with genotype 1 chronic hepatitis C infection. Results of a planned interim,
on-treatment, safety and efficacy analysis (IA) are reported.
Methods:
A total of 332 subjects were randomized into four groups.
·
Group
A received standard of care Peg-IFN 180 mcg/weekly +
RBV 1000-1200 mg, weight-based and TVR-placebo for 48 weeks.
·
Group
B TVR 750 mg q8h together with Peg-IFN+RBV for 12 weeks, followed by Peg-IFN
and RBV for a further 12 weeks.
·
Group
C, TVR 750 q8h with Peg-IFN + RBV for 12 weeks.
·
Group
D, TVR + Peg-IFN for 12 wks. The Roche Taqman assay was used to quantify plasma
HCV RNA (LOD 10 IU/mL).
This first IA was performed when at
least 90% of subjects completed the week 12 visit.
Results:
The median age was 45 years (18-65), median weight 70.9 kg
(45-115), 58.7% were male, 94.1% Caucasian, 7.5 % had stage F3 fibrosis, 34.1%
were infected with genotype 1a, and 54.1% with 1b. The median baseline HCV RNA
was 6.4 Log10IU/ml (3.3-7.7). Overall, discontinuation occurred in 6.4% of
Group A, 17.1% of Groups B+C and 10.5% of Group D subjects prior to week 12.
Discontinuations for AEs, occurred in 2.6% of Group A,
12.5% of Groups B+C and 7.9% of Group D subjects. Pruritis, rash, asthenia,
nausea, and anemia were the most common AEs associated with TVR; anemia and
nausea were less frequent in Group D. The table summarizes ITT viral responses.
Conclusion:
TVR (Telaprevir, VX950)+Peg-IFN+RBV
produces a significantly greater, on-treatment, anti-viral response at weeks 4
and 12 compared to Peg-IFN+RBV in naïve subjects with genotype 1 HCV. Dosing
without RBV reduced the on-treatment anti-viral response; further follow-up
will evaluate effects on SVR and relapse rates. Consistent with prior studies,
the adverse event profile showed that skin events, nausea and anemia are the
most important AE’s associated with TVR. Further results will confirm the
optimal treatment duration and dosage regimen for Phase 3.
|
HCV RNA Un-detectable |
Group A (%) (n=77) |
Groups B+C (%) (n=152) |
Group D (%) (n=76) |
|
Week 4 |
14.3 |
74.3* |
52.6* |
|
Week 12 |
42.9 |
78.9* |
63.2+ |
*p<0.001
compared to Group A; +p=0.015 compared to group A
Topic:
Experimental Treatment – General
A. C. Lyra; M. B. Soares; L. F. da Silva; E. L. Braga;
S. A. Oliveira; M. F. Fortes; A. G. Silva; P. S. Brandão ; B. Genser; R. R. dos
Santos; L. G. Lyra
Introduction:
Studies in animal models of liver disease have shown that
bone marrow cells (BMC) transplantation improves hepatic fibrosis and liver
function. Other authors and we have recently demonstrated that autologous BMC
therapy in patients with chronic liver disease is safe and feasible and may
induce changes in liver function tests.
Aim:
To evaluate the efficacy of BMC transplantation in patients
with advanced chronic liver disease.
Methods:
Thirty patients on the waiting list for liver transplantation
were randomly assigned to receive BMC therapy or no treatment in a nonblinded
fashion. Approximately 50 ml of bone marrow aspirate were prepared by centrifugation
in a ficoll-hypaque gradient. A minimum of 100 millions autologous
mononuclear-enriched BMC were infused into the hepatic artery. Baseline
assessment included clinical, laboratorial and abdominal MRI evaluation. Serum
albumin, bilirubin, INR, Child-Pugh and MELD score were chosen as endpoints to
assess efficacy. Patients were closely assessed for clinical events and changes
in liver function for 90 days. Statistical analysis was conducted by obtaining
descriptive statistics, calculating mean changes from baseline and fitting a
random effects model to compare the profiles of liver tests of both groups.
Results:
Mean age, baseline liver function tests (except for albumin),
MELD and Child-Pugh score were similar in both groups. Albumin levels (g/dl)
were higher in the control group (3.31 vs 2.79, p=0.053). During follow-up one
patient died and one was liver transplanted in the control group while another
patient died in the intervention group. No other major complications were
detected in the remaining patients. Albumin levels increased in the treatment
arm while they remained stable among controls up to 90 days (P=0.034; BMC group
relative change from baseline (RC) = +16%, control group RC = +2%). Child Pugh
score significantly decreased in the therapy group compared to the control
group (P=0.017, BMC group RC = -8%, controls RC = +4%). Bilirubin levels
significantly increased among controls while they decreased in the treatment
arm during the first 60 days after therapy and increased to baseline levels
after 90 days. INR profile was not significantly different between both groups.
Conclusions:
Transplantation of autologous BMC into the hepatic artery
appears to improve liver function of patients with advanced chronic liver
disease at least for up to 90 days and might be a promising treatment option
for these subjects. Larger studies with longer follow-up are necessary to
validate our findings, to define the duration of this beneficial effect and to
determine if there will be improvement of survival.
872.
A New Genotype of Hepatitis C Virus Originating from
D. Murphy; J. Chamberland; R. Dandavino; E. Sablon
The characterization of hepatitis C virus (HCV) variants from
different parts of the world has shown that they can be classified into 6
genotypes. Their distributions differ geographically. Genotypes 1, 2 and 4
display significant genetic diversity in
Methods:
In order to better characterize these variants and to study
their evolutionary relationships with the other genotypes, the entire coding
region sequence of QC69 and partial coding region sequences of CS101285 and
CS101300 were determined. QC69 was isolated from a patient residing in
Results:
This analysis also showed that QC69 was not produced as a
result of recombination events between known genotypes. Further epidemiological
studies based on coding region sequences are required to determine the
prevalence and spread of this genotype in
Conclusions:
The finding of a new genotype in
873.
Outbreak of a new hepatitis C virus subtype (subtype 1m) in a hemodialysis unit
S. Chevaliez; R. Brillet; J. Sehonou; L. Barbotte; J.
Pawlotsky
Introduction:
Nosocomial transmission, especially in the hemodialysis
setting, currently is one of the most frequent causes of hepatitis C virus
(HCV) infection worldwide. We describe an outbreak of a new HCV genotype 1
subtype in a hemodialysis unit, illustrating how new HCV genotypes may spread
in the developing world and further.
Methods:
The 64 patients undergoing regular renal dialysis in the
hemodialysis unit of Hubert Kutuku Maga hospital in
Results:
19 hemodialysis patients out of 64 (29.7%) were HCV-infected;
17 of them were infected with HCV genotype 1, one with genotype 2 and one with
genotype 3. Among the 17 patients infected with genotype 1, 4 (23.5%) were
infected with subtype 1i, one (5.9%) with subtype 1b, and 12 (70.6%) could not
be subtyped. The 4 patients infected with genotype 1i clustered together and
distinctively from other reference genotype 1i strains, suggesting
between-patient transmissions in the hemodialysis unit. In the 12 patients that
could not be subtyped, the sequences were analyzed by a variety of
distance-based, parsimony, and maximum-likelihood methods and evidence was
sought for consistent phylogenetic grouping together and distinctness from
other subtypes. All studied HCV strains were closely related together and segregated
into one monophyletic cluster with high bootstrapping values, suggesting
nosocomial transmission in the hemodialysis unit. Furthermore, these strains
differed from all of the known HCV genotype 1 subtype nucleotide sequences (1a
to 1l) by 16-26% in the NS5B region and 24-33% in the core-E1 region. Since the
cluster members diverged from subtypes 1a to 1l by more than 15% of their
nucleotide sequence, they could be assigned a new, provisional subtype
designation: subtype 1m.
Conclusion:
We report a high prevalence of nosocomial transmission of HCV
in a hemodialysis unit in
875.
Hepatitis C testing, care and treatment: evolution over ten years in
C. Meffre; E. Delarocque-Astagneau; C. Pioche; F.
Dubois; F. Roudot-Thoraval; D. Guyader; C. Silvain; Y. Le Strat; J. Desenclos
Introduction:
With a prevalence of Hepatitis C virus antibodies (anti-HCV)
of about 1% in the population in 1994, hepatitis C was considered as a serious
public health issue by French health authorities that consequently implemented
a national prevention and control program in 1999. To assess its impact we set
up two surveillance systems to 1) monitor trends in anti-HCV screening (Rena-VHC)
and 2) to follow up epidemiological-clinical characteristics of HCV patients
newly referred for care and treatment in hepatology centres
(Pôles-de-Référence) and conducted a population based prevalence survey in
2004. We present the change over time of several key indicators.
Methods:
We used four data sources. Two were national cross sectional
population-based serosurveys of French adult metropolitan residents that
collected risk factors and awareness of HCV infection. Serum samples were
tested for anti-HCV and HCV RNA. The third was Rena-VHC, based on 159
laboratories spread all over France that report number of performed anti-HCV
tests, number of positive tests, age and sex of positive diagnosed persons. The
forth was Pôles-de-Référence which relies on 26 hepatitis C reference centres
and describes clinical and epidemiological characteristics of newly referred
patients, including circumstances of anti-HCV testing, risk exposure for HCV
transmission, HCV RNA serum status and severe liver disease (cirrhosis,hepatocarcinoma).
Results:
|
Prevalence results from
1994 and 2004 |
|||
|
Study Population |
1994 |
2004 |
|
|
|
20-59 year-old |
20-59 year-old |
18-80 year-old |
|
Anti-HCV prevalence (%) |
1.5 (CI95%:0.75-1.34) |
0.71 (CI95%:0.52-0.97) |
0.84 (CI95%:0.65-1.10) |
|
% of HCV RNA + among anti-HCV+ |
81 |
57 (CI95%:40-72) |
65 (CI95%:50-78 |
The proportion of those who were aware of the HCV status:
·
1994,
overall 24%
·
2004,
overall 56%
·
2004
(IDU) 93%
·
2004
(Transfusion < 1992) 72%
·
2004
Others 28%
Treatment:
From 2001 to 2005:
·
Past
excessive alcohol intake remains high (38% in mailes, 11% in females) in
patients newly referred for treatment particularly in those
reporting drug use (50% in males, 30% in females).
·
Proportion
of genotyped patients increased from 55% in 2001 to 83% in 2005.
Conclusion:
From 1994 to 2004:
·
Anti-HCV
prevalence decreased in the general population, which may indicate some impact
of the hepatitis C programme.
·
Proportion
of HCV RNA positive persons deceased, which may be due to improvement of
treatment and therapeutic efficacy.
·
Awareness
of anti-HCV positive status increased which suggests an increase of HCV
screening.
From 2004 to 2005:
·
Increase
of testing from 2000 and decrease of proportion of positive diagnosed persons
from 2003, suggest that rec engtly more persons at lower risk have been
screened.
·
Alcohol
consumption in patients who reported drug use underlines the need of an
integrated treatment of HCV and alcohol dependence.
·
Remaining
high proportion of patients with severe complications (cirrhosis, HCC) when
newly treated, indicates that earlier screening is still warranted for an at
risk patients.
Topic: Epidemiology
C. C. Wang; L. Cook; S. Holte; M. Krows; A. Bagabag;
K. Ng; K. Jerome, ; L. Corey
Objective:
Sexual transmission of hepatitis C (HCV) accounts for
approximately 20% of new infections. Nevertheless, the presence of HCV RNA in
the female genital tract has not been extensively examined; in 3 published
cross-sectional studies, 19-25% of women of childbearing age had detectable HCV
RNA. We sought to define the prevalence of female genital tract HCV RNA
shedding in a prospective study of pre- and post-menopausal women.
Methods:
Women with untreated chronic HCV and detectable serum HCV RNA
were enrolled. Menstrual status and history of hysterectomy were recorded.
Women inserted two Dacron swab into their vaginas every morning as they would a
tampon, placed the swabs into dry cryovials, and stored them immediately in
their home freezers for 18-56 consecutive days. Menstruating women indicated
menstruation dates. HCV RNA and hemoglobin were detected in cervicovaginal
fluids using real-time RT PCR and spectrophotometry, respectively. Statistical
analyses were performed using nonparametric tests and generalized estimating
equations taking into account repeated measures.
Results:
16 women were enrolled; median age was 50 (range 27-59).
Seven women were menstruating, 6 were menopausal, and 3 had had hysterectomies.
Baseline serum VL was 6.43 (range 5.17-7.36 log10 IU/ml) and did not differ by
menstruation or hysterectomy status. Menstruating women were more likely than
menopausal women to have HCV RNA detected in cervicovaginal fluids on at least
one day (86% versus 16%, p=.02). For menstruating women, detection of HCV RNA
was more likely during menstruation (OR= 56.4, 95% CI (23.0,138.3))
or when hemoglobin was detected in cervicovaginal fluids, even when
menstruation was not occurring (OR= 35.4 , 95% CI (12.2,102.6)). The median
quantity of HCV RNA detected in cervicovaginal fluids in menstruating women was
4,631 (range 231-69,580 IU/ml). Only 1 menopausal woman had HCV RNA detected in
cervicovaginal fluids; she also had hemoglobin detected on 8 days during the 56
day sample collection period.
Conclusion:
In women with chronic hepatitis C, HCV RNA detection in
cervicovaginal fluids is associated with menstruation or the detection of
hemoglobin on non-menstruation days. HCV RNA was not detected in women who had
had hysterectomies, suggesting that the presence of the cervix plays a role in
HCV RNA genital tract shedding in women. The quantity of HCV RNA detected was
low, supporting the epidemiologic finding that HCV is not efficiently
transmitted sexually. These findings highlight the fact that HCV is primarily a
blood-borne virus, and may have implications for menstruating women with
chronic hepatitis C.
Topic: Epidemiology
M. E. Hellard; C. Aitken; M. Bharadwaj; S. D. Bowden
Introduction:
Hepatitis C virus (HCV) infection affects an estimated 180
million people worldwide, and causes 50–76% of liver cancers and two thirds of
liver transplants in the developed world. The burden of disease and costs
attributable to HCV-related chronic liver disease will grow due to
complications of cirrhosis and hepatocellular carcinoma in ageing
chronically-infected cohorts and as new HCV infections arise. It is imperative
that research efforts focus on ways to prevent new HCV infections to reduce the
global burden of disease.
Methods:
In Networks II study we established a longitudinal IDU cohort
study; 251 IDUs are followed for two years. Networks II enables us to study HCV
transmission (naive recurrent and and superinfection) and behavioural and
immunological determinants of this and HCV clearance using a social network
approach where the relationship between the IDUs is studied.
Results:
Recruitment commenced in
The traditional (naïve) incidence in our cohort to date is
29.1% per annum (95% CI 17.5, 48.3) and 79.2% (95% CI 25.5, 245.4) in IDUs
injecting for less than one year. The incidence of reinfection was 50.6% pa
(33.3, 76.9) and of superinfection 20.8% pa (12.9, 33.4).
A key driver of HCV infection was having all members of your
network HCV- infected whereas the number of injecting partners and the level of
needle-sharing were less important when measuring disease transmission.
We identified 39 persistently HCV RNA negative people who
injected with >=1 RNA-positive partner, and six who recently injected with a
needle used by >=1 RNA-positive partner; this suggests they possess innate
resistance or develop protective immunity. Our immunological data suggest that
IDUs who clear HCV maintain functionally potent memory CD8+T cells that are
highly cytotoxic and produce antiviral cytokines (IFNg and TNFa); conversely,
CD8+T cells from IDUs with persistent HCV infection are functionally
downregulated with compromised cytotoxic and cytokine secreting capacity.
Conclusion:
The results of Networks II thus far have advance
understanding of the dynamics and immunovirology of HCV infection transmission.
It is our expectation that the study will provide further insights that will
contribute to HCV prevention intervention strategies and vaccine development.
Topic: Epidemiology
877. Barriers
to Healthcare Access Among Chronic Hepatitis C Patients
D. Evon; A. Verma; K. Simpson; S. Smith; M. W. Fried
Purpose:
People with chronic hepatitis C (HCV) may face barriers to
accessing health services. The aims of this study were to determine the extent
to which perceived barriers may complicate HCV care and to examine the
relationship between barriers and socioeconomic (SES) factors.
Methods:
One hundred and twenty eight (n=128) patients referred for
HCV at two hepatology centers completed instruments on a laptop computer during
one of their first two clinic visits. The Barriers to Care Scale (BACS), a
12-item scale with 4 subscales developed for HIV patients, was modified for
this study. Items were rated on a 4-point scale, ranging from 1 (No problem) to
4 (Major Problem) to indicate the extent to which each barrier made it
difficult to access HCV care. Nonparametric tests were used to explore
associations between SES and BACS subscales.
Results:
The majority of participants were male (55%), Caucasian
(81%), married (53%) with a mean age of 46 years. SES characteristics were as
follows: Working full or part-time (70%); Household income of < 40K (56%);
No insurance (11%); Traveled over 30 minutes to clinic (54%); and Lack of
self-transportation (21%). The greatest barriers rated by participants were
lack of personal financial resources, lack of HCV knowledge in their community,
and feeling stigmatized for having HCV. Long distance to a hepatitis facility
and lack of professionals competent in HCV care were also highly rated as
barriers to HCV care (See Table 1). The following associations were found
between BACS subscales and SES factors: 1) Distance was a barrier for unemployed
patients(p=.04) and patients without self-transportation (p=.006); 2) Community
stigma was greater for women compared to men (p=.04); and 3) Personal resources
were a barrier for unmarried patients (p=.001), patients making < 40K
(.000), unemployed patients (p=.001), patients without private insurance
(p=.007), and patients without self-transportation (p=.000).
Conclusions:
HCV patients perceive numerous barriers to accessing HCV
care, which are related in part to SES factors. These data must be considered
when designing interventions to increase access to care for HCV patients.
|
Table 1: Barriers to Care (1= No problem; 4=Major problem) |
Means(SD) |
|
1.
Geographical/Distance - Long
distance to facility - Lack of transportation |
1.9 (.90) 1.4 (.78) |
|
2.
Medical/Psychological - Medical
professionals who do not provide care for HCV - Lack of
professionals who are trained and competent in HCV -Lack of
mental health professionals -Lack of psych/support groups for HCV |
1.6 (.99) 1.9 (.99) 1.4 (.73) 1.6 (.83) |
|
3. Community
Stigma - Level of
knowledge about HCV in community - Community stigma against persons with HCV |
2.3 (1.08) 2.1 (.99) |
|
4. Personal
Resources - Lack of employment
opportunities for people with HCV - Lack of
understanding work environment for people with HCV - Personal
financial resources - Lack of adequate and affordable housing |
1.8 (1.07) 1.8 (1.03) 2.4 (1.10) 1.7 (.94) |
Topic: Epidemiology
886.
Correlates of incident HCV infection and seronegative-immune status in high
risk, IDU prisoners
P. S. Haber; B. Cameron; L. Elliott; S. Teutsch; R.
Ffrench.
Introduction:
High rates of hepatitis C (HCV) infection are reported amongst
prison inmates, primarily linked to injecting drug use (IDU). HCV-specific
cellular immunity is found in a small subset of high risk, seronegative
subjects and may protect against chronic infection. Both factors are likely to
influence incident infection rates and outcomes. The aim of this study is to
determine HCV incidence in seronegative IDU prison inmates, the prevalence of
HCV-specific immunity, and associated risk behaviours.
Subjects and methods:
Adult inmates have been recruited into a prospective cohort –
the Hepatitis C Incidence and Transmission Study-II (HITS-II) study provided
they are: greater than 17 years of age; have a lifetime history of IDU; and
imprisonment and documented negative HCV antibody status within 12 months.
Subjects complete a detailed interview to record demographics and risk
behaviours. Blood is collected to screen for: HCV antibodies by ELISA
(Innogenetics); HCV viraemia (Bayer); interferon-gamma production by
enzyme-linked immunospot (ELISpot) and multiplex in vitro cytokine production
following stimulation with HCV peptides. Thresholds for positive responses were
based on data in low risk, seronegative subjects (n=15). The frequencies of
demographic and behavioural risk factors were compared (SPSS for Windows v.13.0)
Results:
242 inmates have been enrolled, and 184 tested for HCV
antibodies and viraemia. Five had antibody indeterminate status and were
therefore excluded from the analyses. Of the 179 subjects, 39 (22%) had
seroconverted. Female gender (p=0.047), an increased number of incarcerations
(p=0.013), tattooing (p=0.021), and methadone treatment (p<0.0001) were
associated with seroconversion.
Of the 179 subjects, 102 have been tested for HCV-specific
immunity, with 22/78 seronegatives (28%) and 18/24 (75%) seroconverters having
positive responses in the interferon gamma ELISpot. Seronegative-immune status
was positively associated with specific patterns of IDU, and negatively with a
recent break from IDU (all p<0.01). The specificity of the ELISpot responses
differed in that anti-Core, NS2 and NS4a responses were not found in
seronegative-immune subjects. The multiplex assay revealed that
seronegative-immune subjects also had generally low levels of interleukin-10
and high levels of tumour necrosis factor-alpha production in response to NS4-5
stimulation.
Conclusions:
Both incident infection and seronegative-immune status are
common in high risk IDU prisoners. Further follow-up of the subjects in the
HITS cohort will evaluate the details of the predictive risk behaviours and
protective efficacy of the immune responses.
Topic: Epidemiology
889
Community Trends in Diagnosis and Treatment of Hepatitis C
B. P. Yawn1; L. Rocca1; P. Wollan
Introduction:
National data shows decreasing rates of hepatitis C but
little is known about community based rates of recognition and treatment.
Methods:
The Olmsted County, MN hepatitis C registry collects data on
all people diagnosed with hepatitis C residing within the county. The registry is
populated with demographic data, dates of diagnosis, risk factors, contraindications to treatment and treatment information. We
present data on trends for rates of diagnosis, rates of treatment and treatment
contra-indications from our registry.
Results:
The registry includes data on 626 people. The mean age at
diagnosis is 43 years, and gender distribution is 373 men, 253 women and 26%
received hepatitis C treatment. Overall,
123 (2%) had mental health diagnoses.
The incident rate increased in 1995 to 15.5/10,000 person years
(177cases); 2000 to 27.0/10,000 person years (337 cases); 2005 to 27.9/10,000
person years (375 cases).
Rates of treatment of newly identified cases have risen
especially since 2000 (p for trend 0.001). (See Figure) At all times men were
more likely than women to be treated.(p = 0.01) Although newly diagnosed cases
are more likely to be treated, high percentages of previously diagnosed cases
remain untreated due to chronic depression, chronic and relapsing alcohol and
drug addiction. Very few patients were ever reassessed for treatment following
identification of a contraindication.
Conclusion:
·
Hepatitis
C remains common.
·
In
the community, treatment rates have increased but a large percentage of those with
hepatitis C remain untreated.
An increasing prevalence of alcohol dependence and biopolar
disorder are present in those with hepatitis C who are untreated. 
Topic: Epidemiology
S. Currie; H. Shen; N. Brau; B. S. Anand; A. Aytaman; K.
Chang; R. Cheung; T. R. Morgan; M. Pedrosa; W. N. Schmidt; A. Monto1; R.
McQuaid; T. L. Wright; E. J. Bini
Background:
Historically, women have comprised a small percentage of the
veteran population. However, they are now the fastest growing group of
veterans. Because veterans have a higher overall prevalence of HCV than
non-veterans, a better understanding of gender issues and HCV treatment
candidacy may be especially important. Aim: To compare risk factors for HCV
infection and treatment candidacy between women and men veterans.
Methods:
Data were prospectively collected in HCV RNA positive
veterans from 24 Veterans Affairs Medical Centers. Risk factors for HCV were
assessed by questionnaire and treatment candidacy was determined by
standardized criteria. Patients were excluded from treatment if at least one of
thirteen standardized criteria were met.
Results:
Of 4,269 patients, 118 (2.8%) were women. Univariate analyses
showed that women were younger, more educated, and less likely to have a history
of injection drug use, incarceration, heavy alcohol use or snorting cocaine,
but were more likely to have had surgery, a needle stick injury or a blood
transfusion. Despite these differences, baseline laboratory results and
treatment candidacy (43% vs 40%, p = ns) were similar in men and women. Reasons
for exclusion from therapy were similar in men vs women, such as ongoing
substance use (20% vs 13%, p = 0.05), mental health issues (18% vs 19%, p = ns)
and advanced liver disease (14% vs 13%, p = ns), but, as table one shows, men
were more likely to have multiple contraindications to therapy (p<0.05). Men
were also almost twice as likely as women to have 3 or more reasons for
exclusion from therapy (OR=1.69, 95% CI=1.07 - 4.26).
Conclusions:
Women veterans with HCV have fewer high risk behaviors than
men, yet their overall treatment candidacy rates are similar. These seemingly
contradictory results may be due to patients’ exclusion from therapy based on
only on a single contraindication and that women were much more likely than men
to have only one reason for exclusion. These results suggest the need for
gender-specific HCV risk factor screening and counseling, as well as an
opportunity to improve treatment candidacy through substance use and mental
health interventions, especially in women veterans who have fewer
contraindications to HCV treatment.
Table 1. Exclusion criteria met for HCV treatment based on gender (maximum of 13 yes responses) N = 2,450
|
Exclusion Criteria |
Women (n=64) |
Men (n=2,386) |
|
One exclusion criteria met |
51 (79.6%) |
1,665 (69.7%) |
|
Two exclusion criteria met |
12 (18.8%) |
517 (21.7%) |
|
Three or more exclusion criteria met |
1 (1.6%) |
204 (8.6%) |
W. Chen; T. Wong ; G.
Tomlinson; M. D. Krahn, 2; J. Heathcote
Background:
Obesity is considered an important factor contributing to
hepatic steatosis and poor response to anti-viral therapy in patients with
chronic hepatitis C virus (HCV) infection.
Objective:
To determine the prevalence of obesity and explore the
possible factors associated with obesity in a HCV antibody positive,
multicultural tertiary referral clinic population.
Methods:
Patient records describing visits to a downtown tertiary care
liver clinic in
Results:
The 1118 out of 3505 HCV antibody positive patients met our
inclusion criteria. The included patients had a significantly higher prevalence
of obesity (28.8% vs. 14.9%; P<0.001) than the Canadian general population.
After stratification by age and gender, the clinic population remained with a
significantly higher prevalence of obesity than the Canadian general population
in every age/gender category. In the univariate analyses age was positively
associated with high BMI (coefficients 0.073; P<0.001) and obesity (OR
1.020; 95% CI 1.003 to 1.038); Asian origin was negatively associated with BMI
(coefficients -2.187; P<0.001); serum testing for positive HCV RNA was
significantly associated with obesity (OR 1.731; 95% CI 1.075 to 2.788). In the
multivariate regression analyses, age (OR 1.019; 95% CI 1.002 to 1.037) and serum
positive HCV RNA (OR 1.798; 95% CI 1.109 to 2.917) were independent predictors
for obesity. A total of 112 pairs of subjects qualified for matching by
propensity score. The matched propensity score analysis demonstrated that the
subjects with a positive serum HCV RNA test had significantly more obesity
(32.1% vs. 18.8%; p=0.021) than those with a negative HCV RNA test.
Conclusion:
Age and serum HCV RNA (indicating chronic HCV infection)
contribute to the high prevalence of obesity observed in a clinic population
exposed to HCV.