Posters – Tuesday
May 23, 2006 8:00AM Hepatitis C
HCV: Epidemiology, Natural History, Diagnosis
S. Batash;
I. Khaykis; R. F. Raicht;
E. J. Bini
Background:
Inadequate
sterilization and re-use of medical equipment may have contributed to hepatitis
C virus (HCV) transmission in the former Soviet Union. Although New York (NY)
leads the nation in the number of Russian Americans (1.6 million in the NY
Tri-State area), the epidemiology of HCV infection has not been evaluated in
this population. The aims of this study were to determine the prevalence of and
risk factors for HCV infection among Russian immigrants in the NY metropolitan
area.
Methods:
We
conducted a 3-day community-based HCV screening program in the 2 boroughs of
the NY Tri-State area with the highest density of Russian immigrants (Brooklyn
and Queens). Russian radio and cable television were used to invite patients to
come in for free HCV counseling and testing. In the
last 2 days of screening, each person also completed a HCV risk factor
questionnaire.
Results:
The
overall prevalence of HCV positivity among the 283
subjects (age 51.9 ± 15.7 years; 53.4% female) was 28.3% (95% CI 23.0% -
33.5%). Although there was no difference in the prevalence of HCV infection
between men and women (30.3% vs 26.5%, P = 0.48),
there was a linear trend towards an increasing prevalence with age (21.4% in
subjects <30 years old and 35.0% in those ≥70 years old). Among those
who completed the questionnaire, the mean number of years in the U.S. was 10.7
± 6.1, with the majority either from Uzbekistan (32.0%), Ukraine (29.9%), or
Russia (18.6%). Prior injection drug use was uncommon (2.1%), and only 22.7%
reported ≥10 lifetime sexual partners. The prevalence of HCV infection
was 11.1% in immigrants from Russia, 29.0% from Uzbekistan, 31.0% from the
Ukraine, and 36.8% from other regions. Although IM injections (OR=11.1; 95% CI
2.4 - 50.7), blood transfusion (OR=4.3; 95% CI 1.7 - 11.2), hospitalization
(OR=4.2; 95% CI 1.4 - 12.2), and surgery (OR=3.3; 95% CI 1.1 - 9.7) were
significantly associated with HCV positivity in univariate analysis, only IM injections (OR=9.1; 95% CI 2.0
- 42.4) and blood transfusion (OR=3.2; 95% CI 1.2 - 9.0) remained independently
associated with HCV infection in multivariable analysis.
Conclusions:
In
this community-based HCV screening program, we found a high prevalence of HCV
infection among Russian immigrants in the NY metropolitan area. It is likely
that the use of inadequately sterilized medical equipment and blood
transfusions were the primary modes of HCV transmission in this population.
Given the high prevalence of HCV infection in Russian immigrants, universal HCV
testing should be strongly considered in this population.
This study was funded by a grant from Roche
Pharmaceuticals and the American Liver Foundation.
Abstract 550 – Low Prevalence
of Advanced Fibrosis in African americans with chronic hepatitis C and
persistently normal serum ALT : The case for conservative management
A. A. Mihas; M. L. Shiffman; H. R. Lippman; L. Pisney; D. M. Heuman
Background:
African Americans (AA) have poorer treatment responses
than Caucasians (Cau), related to higher prevalence
of genotype 1, higher viral titers, and genetic differences in biology of
interferon response.If likelihood of success with
antiviral therapy is low and disease course is indolent, expectant management
may be preferable to treatment. Currently decisions regarding need for
antiviral treatment are based mainly on liver biopsy, with its attendant risk,
discomfort and cost.
Aims:
The aim of this study was twofold: a) to assess the
spectrum of liver histopathology among AAs with PNALT
as compared to currently high ALT (HALT) or currently normal but intermittently
high ALT (IHALT) and b) to determine whether the relationship of ALT pattern to
fibrosis differs between AA and Cau patients.
Methods:
375 consecutive AA and 206 Cau
US veterans undergoing liver biopsy for evaluation of chronic hepatitis C were
included . We utilized the DVA electronic records to review ALT going back as
much as 23 years, extracting the highest-ever ALT value and the current ALT at
time of liver biopsy. All patients had imaging of the liver as well as routine
biochemical and serologic tests by standard laboratory techniques. Hepatic
fibrosis was graded on a 0-6 scale according to the Ishak staging system by two
blinded reviewers.
Results:
Approximately half the patients with a normal ALT at
the time of liver biopsy were found to have had at least one previous
documented ALT elevation. AA patients with IHALT and HALT had similar fibrosis
scores (2.75 ± 0.15 and 3.1 ± 0.12 respectively), as well as similar prevalence
of advanced fibrosis ( 48% and 54% , respectively) and cirrhosis (14% and 19%,
respectively). In contrast, AA patients with PNALT had significantly lower
fibrosis scores (1.22 ± 0.09, p< 0.01) and prevalence of cirrhosis was only
0.8%. The proportion of patients with PNALT was greater among African Americans
than Caucasians ( 32% vs 22% %, p < 0.05), but in
subgroups with PNALT, IHALT or HALT, no differences were found between races
with respect to mean fibrosis scores or prevalence of advanced fibrosis or
cirrhosis.
Conclusions:
AA are more likely than Cau
to have PNALT. The prevalence of cirrhosis among both AA and Cau with a well-documented PNALT is negligible. If long
term followup is available for an HCV patient and ALT
is persistently normal, liver biopsy is not needed and antiviral therapy can be
deferred . This conservative approach to the PNALT patient is preferable
especially in AA with HCV genotype 1 and high viral titer, in whom probability
of sustained virological response to interferon and ribavirin is low.
Abstract 551 – Spontaneous Clearance of
Hepatitis C Virus Infection in African American Patients
X. Zhao; M. Ramaswamy; M.
Tang; M. Black; X. Ma
Background/Aim:
Spontaneous clearance of hepatitis C
virus (HCV) infection is the outcome of the interplay between host immunity and
virus behavior. HCV has been shown to have different
viral kinetics in African Americans (AA) as opposed to Caucasians. We look at
the spontaneous clearance rate in these two groups and the association of viral
clearance with race, environmental factors, and other viral coinfection.
Method:
Retrospective chart review was
performed on 293 patients with positive HCV Ab who
were followed at our liver clinic from 2002 to 2005. Patients with spontaneous
clearance were identified as having positive HCV Ab
confirmed by RIBA and undetectable viremia without prior treatment; chronically
infected patients were identified as either having active viremia or negative
viremia after treatment. Patients with diagnosed autoimmune diseases were
excluded. Data were collected on patient demographics, risk factors, and
clinical characteristics. Statistical analysis was performed using univariate and multivariate logistic regression analyses.
Result:
There were 191 AA, 74 Caucasians, 19
Asians, and 9 Latin-Americans in our study. The spontaneous clearance rate in
AA and Caucasian patients was 9.4% (18/191) and 20.3% (15/74) respectively
(P=0.021). No difference was observed in age, gender, and weight between the
two groups. In univariate analysis, HBsAg positivity had a positive
association with viral clearance (odds ratio [OR] 6.08; 95% CI 1.56-23.80;
P=0.016); black race (OR 0.45; 95% CI, 0.22-0.91; P=0.027) and alcohol abuse
(OR 0.23; 95% CI, 0.09-0.58; P=0.001) were associated with decreased HCV
clearance; age, gender, and risk factors (IVDA, blood transfusion) did not show
significant association with viral clearance. In multivariate analysis
adjusting for gender, race, alcohol, and HBV coinfection, HBsAg
remained positively associated with viral clearance (OR 14.15; 95% CI
2.74-72.97; P=0.001), while black race (OR 0.42; 95% CI 0.19-0.93; P=0.032) and
alcohol abuse (OR 0.18; 95% CI 0.06-0.52; P=0.001) were still negatively
associated with viral clearance.
Conclusion:
Spontaneous clearance of HCV is lower
in African Americans than in Caucasians; HBV coinfection is associated with
increased likelihood of HCV clearance. The primary viral clearance may be
negatively influenced by black race and alcohol abuse.
Abstract 552 – Prospective and
independent validation of the Lok index for prediction of
cirrhosis in patients with chronic hepatitis C: comparison with FibroScan, Fibrotest and APRI
L. Castera;
J. Foucher; B. Le Bail; P. Bernard; J. Bertet; P. Couzigou; V. de Ledinghen
Background & Aim:
A
novel noninvasive index based on standard laboratory
tests (platelet count, AST/ALT ratio, and INR) has been recently proposed for
prediction of cirrhosis in patients with chronic hepatitis C (CHC) (Lok et al. Hepatology
2005). The aim of this prospective study was to validate independently the
accuracy of this index for the detection of cirrhosis in CHC patients, as
compared with transient elastography (FibroScan) and other serum markers (FibroTest
and APRI).
Patients & Methods:
412
consecutive CHC patients (231 males, mean age 52±12 yrs) who underwent a liver
biopsy at our institution between january 2003 and november 2005 were studied. Of these patients, 264 also had
the day of liver biopsy a FibroScan, a FibroTest, and laboratory tests allowing to calculate the
APRI (AST/platelet) and Lok indexes. These patients
did not differ from the total group for most characteristics including age,
gender, and fibrosis stage distribution. Fibrosis was scored according to
METAVIR by two independent pathologists. Diagnostic performances were assessed
using areas under the receiving operating characteristic curve (AUROC).
Results:
Histological
fibrosis score distribution was : F0-F1 24%; F2 36%; F3 20%; F4 20%. Mean liver
biopsy length was: 19±8 mm. AUROC (95% CI) for the diagnosis of cirrhosis (F4)
of Lok index was 0.81 (0.75-0.87). A Lok index < 0.2 to exclude cirrhosis would have
misclassified 14,5% of patients with cirrhosis (Sensitivity 85%, specificity
43%, negative predictive value 76%), whereas a cut-off > 0.5 to confirm
cirrhosis would misclassify 6% of patients (Sensitivity 50%; specificity 93%;
positive predictive value 64%) ; 195 patients (47%) who were between these 2
values could not be correctly classified. Liver stiffness measurement could not
be obtained in 12 patients (4.5%). In the 252 patients evaluated, AUROC (95%
CI) for the diagnosis of cirrhosis of Lok index was
0.81 (0.74-0.88), compared with 0.95 (0.92-0.98) for FibroScan,
0.86 (0.81-0.91) for FibroTest, and 0.80 (0.73-0.86)
for APRI.
Conclusion:
Diagnostic
performances of Lok index in our patients were
similar to those of APRI but lower than those of FibroScan
and FibroTest. FibroScan
appears as the best method for prediction of cirrhosis in CHC patients.
K. Ario;
T. Mizuta; Y. Eguchi; T. Kumagai;
T. Yasutake; I. Ozaki; K. Fujimoto
Background/Aim:
It
is well recognized that hepatic inflammation facilitates the progression of
hepatic fibrosis and the occurrence of hepatic cancer in HCV-infected patients,
but little is known about the factors associated with hepatic inflammation.
Recent studies have indicated that insulin resistance might be an important
factor related to hepatic fibrogenesis and carcinogenesis. The purpose of this
study was to determine whether insulin resistance influences hepatic
inflammation in patients with HCV-related chronic hepatitis.
Subjects/Method:
Seventy-two
HCV-positive chronic hepatitis patients (44 males, 28 females, mean age:
56.0±9.7, range: 36-73) who underwent liver biopsy and a 75g oral glucose
tolerance test (OGTT) were included. Insulin resistance (or sensitivity) was
evaluated with HOMA-IR and the insulin sensitivity index (ISI composite). Age,
gender, glucose tolerance class (NGT, IGT, DM) in the OGTT, HOMA-IR, ISI
composite, BMI, serum HCV core protein level, HCV genotype (1b, 2a, 2b), serum adiponectin level, histological stage of fibrosis (F1, F2,
F3) and grade of steatosis (<10%, 10-30%, 30-60%, >60%) were analyzed for
their association with serum ALT level and the histological grade of
inflammation (A1, A2, A3) using correlation coefficients, the Mann-Whitney U
test, Fisher’s exact probability test and logistic regression analysis.
Results:
Serum
ALT level was correlated with HOMA-IR (r=0.464, p<0.0001) and ISI composite
(r=-0.352, p=0.002), but not age, BMI, adiponectin
and HCV core protein level. There was no difference in ALT levels according to
gender, glucose tolerance class, HCV genotype, histological fibrosis or
steatosis. Logistic regression analysis showed that HOMA-IR was the only factor
associated with an ALT level of >80 IU/L (OR 3.12, p=0.024). There was a
significant difference in ALT levels between cases with an HOMA-IR of <2 and
>2 (63.9±34.0 vs. 97.2±59.2, respectively; p=0.002). ISI composite was the
only factor related to a histological inflammation grade of >A2 (OR 0.064,
p=0.022). With an ISI composite of <8 and >8, the ratios of those >A2
grade were 83.8% and 25%, respectively.
Conclusions:
The
present study showed that inflammatory activity in HCV-related chronic
hepatitis is strongly related to insulin resistance. These data suggest that
improvements in insulin resistance might lead to decreased inflammation in
HCV-related hepatitis patients.
Abstract 554 – Diagnostic
Liver Biopsy in Patients wWith Advanced Fibrosis and
Cirrhosis
K. E. Sherman; Z. D. Goodman;
S. T. Sullivan; S. Faris-Young
Liver
biopsy is a key modality in the diagnosis and staging of liver disease.
However, optimal biopsy technique in cirrhotic subjects whose samples are prone
to fragmentation and suboptimal interpretation has not been established. We
evaluated the effect of biopsy technique on specimen size, quality and other
features in 923 biopsies in patients with advanced fibrosis/cirrhosis due to
HCV infection.
METHODS:
Liver
biopsy specimens were obtained during the course of a phase II, double-blind
randomized placebo controlled multicenter trial
designed to determine the safety and efficacy of interferon-gamma 1b in
patients with hepatitis C (HCV) associated severe liver fibrosis or cirrhosis
(Ishak stages 4-6). The investigators at individual sites were permitted to
choose the approach and type of liver biopsy performed, but the protocol
specified that specimens should be at least 20 mm in length, to ensure adequate
sampling for evaluation of fibrosis. Biopsies were centrally reviewed. The
following definitions were utilized: Adequate >6 portal tracts, Marginal
3-5 portal tracts, Inadequate <3 portal tracts.
RESULTS:
Needle
type was reported in 826 cases. Cutting needles were used for 595 of the
biopsies (69.7%), aspiration needles for 250 (30%), while the remainder was
unknown or another method. Fragmentation was observed in 39.2% of liver
biopsies obtained using an aspiration technique, but in only 4.7% of samples
collected using an automated cutting needle (p< 0.001). Biopsies performed
with automated cutting needles were judged to be adequate in 553 (93%),
marginally adequate in 36 (6%) and inadequate in 6 (1%). Aspiration biopsies
were adequate in 207 (83%), marginal in 37 (15%) and inadequate in 6 (2%).
Statistically, aspiration methods were much more likely to be judged inadequate
than automated cutting needle techniques (p= 0.005). Mean biopsy length was
19.17 mm (SEM +0.31) across 886 biopsies evaluated. Mean length was
17.47 mm (S.E.M. + 0.52) for aspiration biopsies, 20.26 mm (S.E.M. +
0.37) for automated cutting needle biopsies, and 16.75 mm for other biopsy
types. Analysis of variance indicates that automated cutting needles produced
significant longer biopsies than other types (p<0.05). There were no serious
adverse events associated with liver biopsy in any subject and no procedure
related mortality.
CONCLUSION:
Biopsy
in advanced liver disease more often yields larger, unfragmented
samples amenable to pathologic interpretation when performed with an automated
cutting needle compared to aspiration (suction) biopsy. Adoption of this
technique would facilitate accurate biopsy evaluation in patients with advanced
fibrosis/cirrhosis.