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.
|
|
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.
|
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 (%) |
|