11/12/2005 2pm to 8pm
Abstract ID: 64659
Category: IO2: Liver Imaging Modalities
Validation of an MRI Technique to Measure Liver Fat Content.
S. J.
Cotler, University of Illinois at Chicago, Chicago, IL, G. Guzman, University
of
Illinois
at Chicago, Chicago, IL, J. E. Layden-Almer, University of Illinois at Chicago,
Chicago,
IL, J. Berkes, University of Illinois at Chicago, Chicago, IL, K. Schwartz,
University
of Illinois at Chicago, Chicago, IL, T. Mazzone, University of Illinois at
Chicago,
Chicago, IL, X. Zhou, University of Illinois at Chicago, Chicago, IL
Introduction:
Magnetic resonance imaging
(MRI) has the potential to provide an accurate, noninvasive method to quantify
liver fat, although MRI techniques have not been systematically validated using
liver tissue with known fat content. The aim of this study was to validate an
MRI technique for measuring liver fat.
Methods:
A water phantom and liver
phantoms were scanned before scanning each of 10 human subjects to generate a
standard curve.
Patient Characteristics:
|
Age |
50 ± 11 |
|
Gender
(F/M) |
7/3 |
|
Weight |
86.2 ±
11.7 |
|
BMI (Kg/m2) |
31.9 ±
3.9 |
The liver phantoms consisted
of calf liver homogenized with 0%, 5%, 10%, 20% and 30% corn oil added by
weight. The MRI protocol used a 3.0 Tesla magnet and included fat imaging using
a radio-frequency pulse to saturate the water signal and water and fat imaging
without using any saturation pulses. A fast gradient echo pulse sequence was
used to increase the data acquisition efficiency. The signal intensity from the
water phantom was used as a normalization factor to account for the signal
variations between different study dates, while the signal from the liver
phantoms served as a calibration reference to derive the fat content from the
patients. For human subjects, two regions-of-interest (ROI) were selected in
the right lobe of the liver for calculation of liver fat content and the
results were averaged. Each of the 10 human subjects underwent a liver biopsy.
Image analysis was performed on histologic sections. A computer program was
developed to fit ellipses to fat globules and to calculate the percent of the
area comprised of pixels consistent with fat in a histologic section. A liver
pathologist estimated fat content based on the appearance of the histologic
section used for image analysis. Pearson correlation coefficients were used to
assess the relationships between MRI and image analysis measurements and MRI
and the pathologist’s estimate of liver fat content.
Results:
MRI measurements of the
liver phantoms were highly reproducible with
standard deviations of 0.38%
(0% fat), 0.88% (5% fat), 2.12% (10% fat), 2.97% (20% fat), 5.36% (30% fat),
and 0.32% (100% fat), and were directly related to fat concentration. MRI
measurements of liver fat content in human subjects were strongly correlated
with image analysis of histologic sections (r=0.96, p<0.001) and with a
pathologist’s estimate of liver fat (r=0.93, p<0.001). The pathologist’s
estimates of liver fat content tended to be higher than measurements made by
MRI (median 8.5%, range - 4% to 25%).
Conclusion:
·
The MRI technique validated
in this study provides a non-invasive means to measure liver fat and could be
used to follow changes in fat content over time in response to a therapeutic
intervention.
·
The technique was confirmed over
a range of fat content in human subjects and is sufficiently sensitive to
distinguish patients with NAFLD
·
Standard light microscopy
provided higher estimates of liver fat content than measurements made by MRI or
image analysis.
Abstract ID: 67487
Category: IO2: Liver Imaging Modalities
Amount and type of liver fibrosis detected by stiffness measurements.
M.
Ziol, Jean Verdier Hospital, AP-HP, Bondy, France, N. Barget, Jean Verdier
Hospital,
Pathology Department, Bondy, France, V. Bourcier, Jean Verdier Hospital,
Liver
Unit, Bondy, France, T. Garnier, Jean Verdier Hospital, Liver Unit, Bondy,
France,
M. Beaugrand, Jean Verdier hospital, Liver Unit, Bondy, France
Introduction:
Liver stiffness measurement
(LSM) is a new, non invasive method that has been demonstrated to detect
significant liver fibrosis in patients with chronic hepatitis C.
Aim:
We aimed to investigate in a
large cohort of patients with various chronic and acute liver diseases the
relation between LSM using elastography and collagen deposition quantified on
liver biopsies.
Methods:
Two hundred and seventy
patients referred to our institution for liver biopsy whatever the suspected
cause of the disease were included. LSM was performed in all patients within
less than 3 months before or after biopsy. To avoid sampling error, less than
20mm long liver biopsies were excluded. We quantified collagen deposition using
computer assisted image analysis on 5 micrometers thick picrosirius red stained
sections. The fibrosis area fraction (FAF) was assessed using interactive
thresholding of greyscale converted digital images of 10 consecutive fields
(X100) for each liver biopsy. Taking in account clinical data and histological
analysis, patient’s liver biopsies were classified as follows: no architectural
abnormalities, chronic hepatitis (portal fibrosis), biliary type fibrosis,
alcoholic liver disease or non alcoholic steatohepatitis and abnormalities of
liver-cell plates without fibrosis.
Both FAF (%) and LSM
(kilopascals) were available in 211 patients. LSM values ranged from 2.8 to
75.4 kPa (mean +/-SD:9+/-13) and fraction of fibrosis area from 0.13 to 49%
(3.3+/-7). Fraction of fibrosis area was significantly correlated to LSM
(Spearman correlation coefficient Rho=0.608; p<0.0001).
Results:
All except one patient in
the group without architectural abnormalities (acute hepatitis, granulomas,
steatosis without fibrosis; n=24) had low LSM values (5.9+/-3.2kPa). When
patients were divided into groups according to the etiology and related
architectural abnormalities, significant correlation was found between LSM and
FAF in chronic hepatitis (n=121, Rho=0.66, p<0.0001) and alcoholic liver
disease or non-alcoholic steatohepatitis (NASH) (n=37, Rho=0.64, p=0.0001). In
patients with abnormalities of liver cell plates without fibrosis on liver
biopsies (nodular regenerative hyperplasia, incomplete or macronodular
cirrhosis; n=25), LSM values were
highly scattered, varying
from 3 to 46kPa.
Conclusion:
Using both quantitative
morphometric evaluation of liver fibrosis and qualitative assessment of
architectural abnormalities as a gold standard, our results suggest that LSM
accurately reflects liver fibrosis observed in chronic hepatitis and alcoholic liver
disease or NASH.
Abstract ID: 63689
Category: IO2: Liver Imaging Modalities
Assessment of Hepatic Fibrosis in Chronic Liver Disease — Usefulness of the StrainRate Imaging Method
N.
Hotta, Aichi Medical University, Nagakute, Japan, A. Okumura, Aichi Medical
University,
Nagakute, Japan, T. Ishikawa, 21 Karimata, Nagakute, Japan, S. Kakumu,
Aichi
Medical University, Nagakute, Japan
Purpose:
The development of hepatic
fibrosis in patients with chronic liver disease
increases the risk of liver cancer.
Assessing the degree of hepatic fibrosis is therefore one of the most important
factors in therapeutic planning. Conventionally, liver biopsy is performed to
assess hepatic fibrosis, but this method is associated with complications such
as hemorrhage. The present study was conducted to determine whether an easily
performed myocardial examination technique can be applied to the assessment of
hepatic fibrosis. Strain Rate Imaging is a new method based on Tissue Doppler
Imaging (TDI). This method is useful for eliminating the effects of
translational motion or tethering of the myocardium and for evaluating the
local contraction and expansion of the myocardium. The strain value is
calculated by dividing the change in the length of an object before and after
motion by the length before motion. The usefulness of Strain Rate Imaging in
assessing the degree of hepatic fibrosis was evaluated.
Methods:
Strain Rate Imaging was
performed using a diagnostic ultrasound system
(AplioTM, Toshiba Medical
Systems Corporation, Tochigi, Japan) in a total of 30 subjects: 17 in the
chronic hepatitis group, 8 in the cirrhosis group, and 5 in the normal control
group. Dynamic images were acquired as raw data in Harmonic TDI mode, in which
the harmonic components are used for data transmission/reception. Similar to
the Tissue Harmonic method used in B-mode imaging, Harmonic TDI improves the
accuracy of TDI velocity values and suppresses artifacts. TDI-Q, the Tissue
Doppler analysis software installed in the Aplio system, was used for analysis.
Measurement was
performed five times from
the epigastrium, with the ROI size set to 10 mm and the derivative pitch to 3
mm. The mean of the five measurements was used as the strain value.
Results:
The mean strain value was
0.204 in the chronic hepatitis group, 0.078 in the
cirrhosis group, and 0.32 in
the normal control group.
Conclusion:
The results of the present
study suggest that this noninvasive method permits
quantitative assessment of
the degree of hepatic fibrosis to be performed easily and in a short time. It
is expected that the accuracy of the Strain Rate Imaging method in determining
the degree of hepatic fibrosis will be improved when it is used in combination
with histological examination.
Abstract ID: 65302
Category: IO2: Liver Imaging Modalities
Prospective randomised comparison of mini-laparoscopy and percutaneous liver biopsy. Analysis of 1000 examinations. Diagnosis of cirrhosis and complications.
U.
Denzer, Medical department I, university medical center Hamburg Eppendorf,
Hamburg,
Germany, A. Arnoldy, I Medical department Johannes Gutenberg University
Mainz,
Germany, Mainz, Germany, Germany, U. Weickert, Medical department C,
Medical
center Ludwigshafen, Germany, Ludwigshafen, Germany, Germany, S.
Kanzler,
I Medical Department, University Mainz, Germany, Mainz,Germany, Germany,
P. R.
Galle, I Medical Department, University Mainz, Germany, Mainz, Germany, J. F.
Riemann,
medical Department C, Medical Center Ludwigshafen, Germany,
Ludwigshafen,
Germany, H. P. Dienes, Institution for Pathology, University Medical
Center
Köln, Germany, Koeln, Germany, Germany, A. W. Lohse, Medical center I,
University
Medical Center Hamburg Eppendorf, Hamburg, Germany, Germany
Introduction:
Percutaneous liver biopsy is
the gold standard for gaining liver histology in
chronic liver disease (pLB).
Nevertheless false negative biopsy rates in cirrhosis range from 10 - 50 %.
Diagnostic mini-laparoscopy (optic 1.9 mm) (ML) is an alternative procedure
with the advantage of additional macroscopic evaluation. This study compared
both methods prospectively and randomized.
Methods:
Patients gave written
informed consent. Exclusion of severe coagulation
disorders. Liver biopsy: Vim
Silverman needle (ML); Menghini needle (pLB) (biopsy diameter 1.4 mm).
Macroscopic liver evaluation documented as normal, fibrosis/irregular cirrhosis
and cirrhosis. Formalin fixed paraffin embedded sections were stained with
H&E and IVG. The slides were blindly coded and graded (HAI score). Controls
day 1 after biopsy: Blood count and ultrasound.
Results:
Patients: 1000 patients were
randomized (9/00 - 7/04), study drop out: 75. Biopsy groups showed comparable
demographic and clinical characteristics of patients. Indication for liver
biopsy: cHCV: 48,8 % (ML) 41.8 % (pLB); Hepatopathy of unknown origin: 29 %
33,3 %; cHBV: 10 %, 29,8 %; AIH / PBC/ PSC: 11,4 %, 10,7%; others: 1,3 %, 0,6
%. Diagnosis of cirrhosis: Criteria for
cirrhosis: PLB: Modified Ishaak score 5 or 6; ML: Combination of macroscopic
(irregular cirrhosis scored as fibrosis) and histologic scoring. Available for
blinded histologic scoring pLB in 410 cases, ML in 401 cases. No significant
difference in length of biopsy specimen, marginally difference in count of
portal fields per specimen. Comparison of blindly coded liver histology
resulted in no significant differences in histologic grading (No liver
fibrosis: score 0 vs. liver fibrosis: score 1-4 vs. liver cirrhosis: score 5-6;
p = 0.34;). Histologic grading revealed the diagnosis liver cirrhosis in pLB in
23.0 % (n = 94) compared to ML in 25.3 % (n = 103). Comparison of histologic
staging in pLB and combined macroscopic /histologic staging in ML resulted in a
significant higher rate of 10 % more frequently diagnosed liver cirrhoses with ML
procedure. pLB diagnosed liver cirrhosis in 22.9 % (n = 94) compared to ML in
33.2 % (n = 133) (p = 0.001). Complications: PLB: Severe (requiring hospital
stay longer than one day): 0.9 % (Hemobilia: 1; post biopsy bleeding: 3). ML:
0.2 % (Hemobilia: 1) p = 0.188 ns. (table 3). Ultrasound control day 1:
Intraabdominal fluid (3.4 % vs. 1.4 %, p = 0.068) and intrahepatic hematoma
(2.0 % vs. 2.1 %, p = 1.00).
Conclusion:
Mini-laparoscopic evaluation
diagnoses of about 10 % more liver cirrhoses.
Mini-laparoscopic liver
biopsy is shown to be safe and superior in staging of liver diseases.
Abstract ID: 65144
Category: IO2: Liver Imaging Modalities
Prevalence and factors associated with failure of liver stiffness measurement using FibroScan® in a prospective study of 2114 examinations.
J.
Foucher, Hopital haut-Leveque, Pessac, France, L. Castera, Hopital
Haut-Leveque,
Pessac,
France, D. Laharie, Hopital Haut Leveque, Pessac, France, N. Le Provost,
Hopital
Haut Leveque, Pessac, France, P. Couzigou, Hopital Haut Leveque, Pessac,
France,
P. Bernard, Hopital Saint-Andre, Bordeaux, France, X. Adhoute, Hopital Haut
Leveque,
Pessac, France, V. de Ledinghen, Hopital Haut-Leveque, Pessac, France
Background & aims:
Recently, we have shown that
liver stiffness measurement (FibroScan®,
of liver fibrosis. However,
in around 5% of cases, no value could be obtained. The aim of this prospective
study was to assess the prevalence and factors associated with failure of liver
stiffness measurement.
Methods:
All patients with chronic
liver disease and liver stiffness measurement between May 2003 and April 2005
were included. Failure of liver stiffness measurement was defined as no value
obtained after 10 measurements. Clinical and biological factors associated with
failure were analyzed using Chi-square, t-Student test, and logistic
regression.
Results:
2114 liver stiffness
measurements were analyzed. Characteristics of patients
were: 1168 males, mean age
52 ± 13 years, BMI 24.4 ± 4.4 (range: 12-49). Indications for FibroScan® were
HCV (55.5%), HBV (5.5%), alcohol (9%), NASH (3.6%), hemochromatosis (2.4%),
miscellaneous (24%). Median value of FS was 6.8 kPa (range: 1.5 – 75 kPa).
Failure was observed in 4.5% of cases. By univariate analysis, factors
associated with failure were BMI > 28 (OR 9.1, 95%CI 5.8-14.0, p<0.001),
diabetes (OR 2.1, 95%CI 1.2-3.7, p=0.01), age > 50 years (OR 4.0, 95%CI
2.7-6.3, p<0.001), NASH (OR 3.4, 95%CI 1.7-6.9, p=0.001), and gGT level (OR
2.0, 95%CI 1.3-3.1, p=0.002).
Failure was not associated
with operator, gender, or transaminases level. By multivariate analysis, the
only factor aasociated with failure was BMI > 28 (OR 10.0, 95%CI 5.7- 17.9,
p=0.001).
Conclusion:
·
Liver stiffness measurement
was successful in 95.5% of cases
·
The only factor associated
with failure is obesity. However, FibroScan®
is feasible even in severely obese patients (BMI=49)
·
Other non-invasive methods
of liver biopsy could be used only in patients with failure of FibronScan®
examination.
Abstract ID: 62900
Category: IO2: Liver Imaging Modalities
Non-invasive detection of cellular proliferation in the woodchuck model of hepatocellular carcinoma.
E.
McKenzie, National Research Council of Canada - Institute for Biodiagnostics,
Winnipeg,
Canada, J. Sun, National Research Council - Institute for Biodiagnostics,
Winnipeg,
Canada, M. Jackson, National Research Council - Institute for Biodiagnostics,
Winnipeg,
Canada, M. L. Gruwel, National Research Council - Institute for
Biodiagnostics,
Winnipeg, Canada
Introduction:
Carcinogenesis can be
measured in the livers of woodchucks chronically
infected with woodchuck
hepatitis virus (WHV) through repeated magnetic resonance imaging (MRI) and localized
phosphorus spectroscopy (31P-MRS), and the results of the MRS can be correlated
with the degree of liver injury detected by serum gamma glutamyltransferase.
Methods:
Prior to imaging, serum
samples were collected from the hind limb of each
woodchuck for analysis of
gamma glutamyltransferase concentration, viral load and expression of woodchuck
hepatitis surface antigen (WHsAg). A custom-built doubly tunable quadrature
volume coil was tuned and matched to 300MHz and 121.5MHz for proton imaging (1H-MRI)
and phosphorus spectroscopy (31P-MRS) respectively to image age- and
sex-matched control (n=5) and chronically infected (n=5) adult woodchucks in a
7T horizontal bore magnet (Magnex, UK). Sagittal and axial scout FLASH images
(128x128, slice thickness = 5mm, TR/TE=1000/4.1ms, 8 averages) were acquired to
locate the largest portion of liver with the least amount of signal
contamination from surrounding muscle and adipose tissues. Two-dimensional
chemical shift imaging (2D-CSI, 16x16 data matrix, 24x24x2cm, 1024 data points,
TR=1000ms, 16 averages) was acquired for all woodchucks each month for a six
months period.
Results:
Cellular proliferation
within the tumours of infected woodchucks was detected as an increase in the
ratio of the amounts of phosphomonoesters relative to the b phosphate group of
ATP (p=0.01). Significantly elevated levels of serum gamma glutamyltransferase
indicated hepatocyte injury in chronically infected woodchucks (p=0.02). An
active chronic infection was confirmed by viral load and the expression of
WHsAg in infected animals.
Conclusions:
Repeated imaging of
chronically infected woodchucks can detect changes
in liver tissue composition using proton imaging and phosphorus spectroscopy. Liver injury can be correlated to the expression of gamma glutamyltransferase.
Abstract ID: 65541
Category: LO1: Public Policy, Epidemiology, and Decision Analysis
Administration of Erythropoietin for Hepatitis C Treatment-Related Anemia Is Not Cost Effective.
M. S.
Campbell, University of Pennsylvania, Philadelphia, PA, J. C. Sun, University
of
Pennsylvania,
Philadelphia, PA, B. Y. Lee, University of Pennsylvania, Philadelphia,
PA,
D. E. Kaplan, University of Pennsylvania, Philadelphia, PA, K. Reddy,
University
of
Pennsylvania, Philadelphia, PA
Aim:
To determine the
cost-effectiveness of erythropoietin administration to genotype 1 hepatitis C
patients with advanced fibrosis who develop treatment-related anemia.
Methods:
We constructed a 7-state
lifetime Markov cost-effectiveness model with 1
year cycle length. Patients
cycled between bridging fibrosis, compensated cirrhosis, hepatocellular
carcinoma, decompensated cirrhosis, liver transplantation, and death. Competing
age-adjusted mortality was included. Transition probabilities, quality of life
measurements based on standard gamble data, and costs were obtained from
systematic literature review. We used wholesale drug costs and performed the
analysis from a Medicare payer perspective (2003 US dollars). Base case was a
50 year old anemic patient (hemoglobin < 12 mg/dL) with at least bridging
fibrosis. We assumed that 80% of patients who receive erythropoietin and 46% of
those who do not receive erythropoietin were able to maintain recommended
weight-based pegylated interferon and ribavirin dosages (
erythropoietin and 42.6% who
are not given erythropoietin achieved sustained virologic response (Reddy KR et
al J Hepatol abstract 2005). We accounted for treatment discontinuation due to
lack of early virologic response. We performed
Results:
For a 50 year old with
metavir 2 fibrosis, our Markov model yielded median survivals of 31 and 25
years for patients who did not respond to HCV therapy, respectively. Ten year survival for compensated cirrhotics
not responding to therapy was 71%.
Incremental cost effective
ratio (ICER) for administration of erythropoietin during HCV therapy were
$77,313, $61,886, and $66,674 for patients with metavir stage 2 fibrosis,
bridging fibrosis, and compensated cirrhosis, respectively . One way sensitivity analysis showed that age,
effect of erythropoietin in sustained virological response and on quality of
life (utility) during treatment, cost of treatment with and without the use
erythropoietin, transition possibilities from compensated to decompensated
cirrhosis to hepatocellular carcinoma (HCC), and discount were associated with
the largest ranges in ICER.
For erythropoietin
administration to be cost effective (<$50,000), the incremental improvement
in sustained virological response must be 5.7% or greater. The base case assumes the erythropoietin
improves sustained virological response by 3.8%.
Conclusions:
Our comprehensive Markov
model suggests that administration of
erythropoietin is not
cost-effective for hepatitis C patients with advanced fibrosis who develop
treatment-related anemia. The small gains in response rate are eclipsed by the
large increase in cost of therapy due to the addition of erythropoietin.
Abstract ID: 64853
Category: LO1: Public Policy, Epidemiology, and Decision Analysis
HIV Testing and HIV Seropositivity Among Patients with Chronic Hepatitis C Virus Infection: Missed Opportunities for Early Diagnosis.
G.
Villanueva, Bellevue Hospital and NYU School of Medicine, New York, NY, N.
Shukla,
NYU School of Medicine, New York, NY, C. T. Tenner, VA New York Harbor
Healthcare
System and NYU School of Medicine, New York, NY, A. Aytaman, VA
New
York Harbor Healthcare System, Brooklyn, NY, E. J. Bini, VA New York Harbor
Healthcare
System and NYU School of Medicine, New York, NY
Background:
Coinfection with hepatitis C
virus (HCV) and human immunodeficiency virus (HIV) is a major public health problem
worldwide. The 2002 National Institutes of Health HCV Consensus Conference
recommended that patients with HCV infection who are at risk for HIV should be
offered HIV testing. To date, however, little is known about HIV testing in
this population. The aims of this study were to determine the proportion of
patients with chronic HCV infection who were tested for HIV and to evaluate the
frequency of HIV seropositivity in this population.
Methods:
569 patients with chronic
HCV infection and 670 HCV antibody negative controls completed a survey at the
time of their outpatient clinic visit at 3 study sites. Data collected included
patient demographics, risk factors for HCV and HIV infection, and information
regarding prior HIV testing.
Results:
Overall, the mean age of the
1,239 patients was 55.2 ± 10.3 years, 80.8% were men, and the population was
ethnically diverse with 36.5% non-Hispanic whites, 37.4% non-Hispanic blacks,
19.6% Hispanics, and 6.5% who reported their ethnicity as “other”. Of the 569 HCV(+)
patients, 62.6% were tested for HIV, 35.7% were never tested, and 1.8% did not
know if they were tested and this differed significantly (p <0.001) from
HCV(-) patients (43.9%, 49.4%, and 6.7%, respectively). Among HCV(+) patients,
the proportion tested for HIV decreased with age (p <0.001), was more common
in men than in women (70.0% vs. 38.4%, p <0.001), and differed according to
ethnicity (p = 0.001). Importantly, risk factors for HIV infection were common
among the 203 HCV(+) patients who were never HIV tested, including injection
drug use (68.0%), ³10 lifetime sexual partners (58.1%), sex with a prostitute
(58.1%), and sex with a same-sex partner (13.3%). Of the HCV(+) patients who
were tested for HIV, 23.9% were positive, 74.2% were negative, and 2.0% did not
know the results of their HIV test; this differed significantly (p = 0.04) from
HCV(-) patients (16.0%, 81.3%, and 2.7%, respectively). Among HCV(+) patients,
the proportion that tested positive for HIV did not differ according to age (p
= 0.27), but was higher in women than in men (41.9% vs. 21.9%, p = 0.004) and
differed according to ethnicity (p = 0.049).
Conclusions:
Although HCV(+) patients
were more likely to be tested for HIV than HCV(-) subjects, missed
opportunities for early diagnosis of HIV infection exist. The high prevalence
of HIV seropositivity and risk factors for HIV infection in patients with HCV
suggests that the current testing guidelines should be revised to recommend
universal HIV testing for all HCV infected persons.
Abstract
ID: 64395
Category:
LO1: Public Policy, Epidemiology, and Decision Analysis
Quality-of-life tradoffs for hepatitis C treatment: do patients and health professionals agree?
B. R.
Schackman, Weill Medical College of Cornell University, New York, NY, P. A.
Teixeira,
Weill Medical College of Cornell University, New York, NY, G. Weitzman,
Weill
Medical College of Cornell University, New York, NY, A. I. Mushlin , Weill
Medical
College of Cornell University, New York, NY, I. M. Jacobson, Weill Medical
College
of Cornell University,
Purpose
To investigate differences between how HCV patients
and health professionals in an urban setting evaluate the quality-of-life
tradeoffs associated with HCV treatment.
Methods
Hypothetical descriptions of HCV disease symptoms and
of treatment side
effects were presented to 1) 92 treatment-naïve HCV
patients recruited at gastroenterology, methadone maintenance, and HIV clinics
at 3 urban hospitals; and 2) 23 health care professionals experienced in
treating HCV patients. Respondents performed rating scale (RS) and standard
gamble (SG) evaluations of the health states on a scale from 0 (death or worse
than death) to 100 (best possible health). Evaluations were in English and
Spanish.
Results
78% of patients and 83% of professionals were able to
complete all the evaluations. Treatment
side effects were rated worse by patients than professionals using both evaluation
methods (p<0.02). RS responses indicated that a year of severe treatment
side effects was equivalent to 4.3 years of mild chronic HCV symptoms for
patients versus 1.9 years for professionals; a year of moderate treatment side
effects was equivalent to 1.5 years of moderate chronic HCV symptoms for
patients versus 0.7 years for professionals. SG responses were similar. For the
44 patients with depression (10-item CES-D score ³ 10), the implied value of
HCV treatment was low unless it would also relieve their depression.
Conclusions
Health professionals have fewer concerns about HCV
treatment side effects than patients. Peer-led counseling and pre-treatment of
depression may improve patient acceptance of quality-of-life tradeoffs
associated with initiating HCV treatment. Conversely, helping physicians to
recognize patients’ perceptions may also lead to improved communication and
higher treatment acceptance rates. In
addition, patients with symptoms of depression represented 60% of the sample
and their responses indicating the importance of relieving depressive symptoms
to their consideration of HCV treatment.
Abstract ID: 62351
Category: LO1: Public Policy, Epidemiology, and Decision Analysis
Coffee Drinking Decreases the Risk of Chronic Liver Disease in the United States Population.
C. E.
Ruhl, Social & Scientific Systems, Inc., Silver Spring, MD, J. E. Everhart,
National
Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD
Purpose:
Coffee drinking has been
suggested to protect against liver injury, but it is
uncertain whether this is of
clinical significance. We examined the relationship of coffee and tea
consumption with the incidence of hospitalization or death from chronic liver
disease (CLD).
Methods:
Participants in the
population-based first National Health and Nutrition
Examination Survey, 1971-75,
were asked about their typical total coffee and tea consumption. Daily coffee
and tea intake was categorized as <1 cup (mean 0.2 cups), 1-2 cups, and
>2 cups (mean 4.0 cups). A second analysis included follow-up of persons
free of liver disease in 1982-84 who were asked more detailed questions on
coffee and tea drinking. Persons with evidence of liver disease at baseline
were excluded. Participants were followed through 1992-93 for CLD as identified
by hospital or death certificate diagnosis of CLD or cirrhosis (ICD-9-CM 571).
Ninety-six percent of the baseline cohort was recontacted. Hazard rate ratios
for CLD according to coffee and tea intake level were calculated using Cox
proportional hazards analysis.
Results:
9,849 persons were followed
for a median of 19.0 years (range 0.02-22.1). Cumulative incidence of CLD was
1.4% at 20 years. Participants who
consumed more coffee and tea had a lower incidence of CLD (test for trend
p=0.002) (Figure). In multivariate analysis, participants who drank >2 cups
per day had less than half the rate of CLD as those who drank <1 cup per day
(hazard ratio = 0.43, 95% confidence interval = 0.24-0.78). Protection by
coffee and tea was limited to persons at higher risk for liver diseases from
heavier alcohol intake, overweight, diabetes, or high iron saturation. Among
9,650 participants who provided detailed drink information in 1982-84, intake
of regular ground coffee and of caffeine was associated with lower incidence of
CLD.
Conclusions:
Coffee and tea drinking
decreases the risk of clinically significant CLD. Further investigation into the mechanism and
potential clinical benefit of this relationship should be pursued.
Abstract ID: 62378
Category: LO1: Public Policy, Epidemiology, and Decision Analysis
The Cost of Variceal Bleeding in Cirrhosis - A Comparison of a Decision Based Economic Model and Patient Data.
L. M.
Cheshire, University College London, UK, London, AK, United Kingdom (Great
Britain),
R. Jalan, University College London, London, AK, United Kingdom (Great
Britain)
Objective:
A bottom-up cost analysis of
direct health care resource utilization was
carried out in a sample of
patients presenting with oesophageal variceal bleeding and compared with the
predicted cost of managing a bleed from a decision analysis model.
Methods:
The decision analysis model
was developed in Excel®. Treatment strategies
for the model were based on
the ‘UK guidelines on the management of variceal haemorrhage in cirrhotic
patients’ (Jalan & Hayes 2000). Clinical outcomes and probabilities were
derived from the literature and physician interviews. Sensitivity analysis was performed
to evaluate the effect of changes in resource use or unit costs. For the
patient analysis, data was collected from 31 patients case notes, each having
experienced an acute episode of variceal bleeding requiring endoscopic therapy.
Resource data on: length of stay; blood product use; medication; consultations;
and tests/procedures were collected. Data sources were medical/nursing notes,
charts and electronic records. The main unit of analysis was an ‘episode of
care’, defined as starting with index bleed and continuing for a 42-day
follow-up period, or death.
Results:
In the patient analysis,
mean survival at 42 days was 55% vs. 54.8% in the model. Out of the 31 initial
bleeds, there were a further 11 re-bleed/new bleeds; 8 (26%) patients required
transjugular intrahepatic portosystemic stent shunt (TIPSS) insertions for
uncontrolled bleeding. Mean cost of an episode of care was £17,738 in the
patient analysis vs £15,595 in the model; the actual cost of a life saved is
£32,345. Non-survivors cost significantly
more on a mean daily cost
basis (p=0.0007). Disease severity impacted on cost, although this was not
incorporated into the model. Major cost drivers in both model and patient data
were length of stay, especially intensive care, use of blood products and
number of procedures/investigations carried out. Patient analysis reflected
these estimates and findings in the decision model.
Conclusion:
There was good concordance
between the economic model and actual
patient data, making it an
extremely powerful tool to evaluate the cost of different clinical scenarios.
Variceal bleeding carries a burden of disease to both individuals and health
service providers. To bring down costs, management strategies need to be found
to reduce length of stay and improve control of initial bleeding, whilst
preventing further rebleeding.
Abstract ID: 64466
Category: LO1: Public Policy, Epidemiology, and Decision Analysis
Impact of Patient Race and Gender on the Care of a Large Cohort of Community Based Hepatitis C Patients.
T. M.
Shehab, Huron Gastro, Ypsilanti, MI, R. R. Randhawa, St. Joseph Mercy
Hospital,
Ypsilanti, MI, A. M. Jankowski, Huron Gastro, Ypsilanti, MI, R. L. Stoler,
Huron Gastro, Ypsilanti, MI
Introduction:
Previous research has
demonstrated that patient race and gender affect the
management of a number of
diseases. While race affects the efficacy of hepatitis C therapy, the impact of
race and gender on the care of hepatitis C patients has not been assessed. The
aim of this study is to determine if race and gender influence the provision of
care (diagnostic evaluation/treatment) of a large cohort of patients seeking
consultative care for hepatitis C in a community based, private practice
gastroenterology group.
Methods:
Retrospective chart review
was performed for all patients referred for evaluation of hepatitis C between
1997 and 2002. The review assessed patient demographics, laboratory evaluation,
disease severity and treatment response (Interferon/Ribavirin or Pegylated
Interferon/Ribavirin).
Results:
670 patients ( male=396;
female = 274)were seen for an initial consultation for hepatitis C during the study
period. 59% of patients were male, 538
patients or 80% were Caucasian (Cauc), 101
patients or 15% African-American (AA) and mean age was 47 ± 10.0 (17-90)
years. A statistically significant difference (p<0.05) was seen between Cauc
and AA patients in the following categories: BMI, proportion of patients who
returned for a
second office visit,
compliance with office visits, genotype and sustained virologic response (SVR).
The mean number of office visits during the study based on race/gender was: 5
for Cauc men and women, 4 for AA women and 2 for AA men. There was no
significant difference in indication for referral, rates of viremia, diagnostic
evaluation, proportion of patients offered therapy or proportion of patients
with elevated liver enzymes based on race or gender. The patient’s gender did
not affect the proportion of patients with advanced fibrosis, elevated liver
enzymes or likelihood of
receiving hepatitis C
therapy.
Conclusion:
Race had a significant
impact on a number of factors that are important in the care of hepatitis C
patients. In addition to lower rates of virologic response, African-American
patients had fewer office visits and were less likely to return for a second
office visit. The disparity was even more significant in African American men.
Overall, gender had little impact on the evaluation, histologic severity and
initiation of treatment. While much attention has been focused on the impact of
race on treatment response, further research must clarify barriers that may
negatively affect the care of
certain subgroups of
hepatitis C patients.
Abstract ID: 64997
Category: LO1: Public Policy, Epidemiology, and Decision Analysis
Cost-effectiveness of treatment for chronic hepatitis C infection in patients coinfected with human immunodeficiency virus
J. C.
Servoss, GI Unit, Massachusetts General Hospital, Boston, MA, N. G. Campos,
Harvard
University Initiative for Global Health, Cambridge, MA, J. A. Salomon,
Harvard
University Initiative for Global Health, Cambridge, MA, K. A. Freedberg,
Massachusetts
General Hospital, Boston, MA, J. H. Samet, Boston Medical Center,
Boston,
MA, S. J. Goldie, Harvard University Initiative for Global Health, Cambridge,
MA,
R. T. Chung, GI Unit, Massachusetts General Hospital, Boston, MA
Background/Aim:
Antiviral therapy with
pegylated interferon-alpha and ribavirin has been recently approved for
treatment of hepatitis C virus (HCV) in human immunodeficiency virus
(HIV)-coinfected persons. However, in view of more limited efficacy rates in
coinfection, the cost-effectiveness of this treatment merits investigation. We
sought to examine the clinical benefits and cost-effectiveness of treatment for
chronic HCV infection in patients co-infected with HIV.
Methods:
We modified the natural
history, HCV treatment efficacy and cost parameters of an existing Markov model
of HCV monoinfection to reflect coinfection with HIV and recent randomized
clinical trial data. The two treatment strategies examined were 48 weeks of
combination therapy with: (A) pegylated interferon-alpha and ribavirin or (B)
interferon-alpha and ribavirin. Outcomes included life expectancy and
cost-effectiveness
in incremental cost per
life-year saved.
Results:
Treatment with pegylated
interferon alfa 2a and ribavirin was consistently more effective and cost
effective than treatment with interferon alfa-2a (standard interferon) and
ribavirin. For a hypothetical cohort of
HIV/HCV coinfected patients with CD4 count 200-500 cell/mm3, treatment with pegylated
interferon alfa 2a and ribavirin yielded life expectancy gains from 2 months
(genotype 1 HCV) to 11 months (non-1 genotype HCV). Incremental cost effectiveness ratios,
stratified by genotype and weighted by sex, ranged from $160,000 Genotype 1 to
$35,600 for non-genotype 1 patients.
Because the overall higher efficacy of HCV treatment in those with
non-genotype 1 HCV, the incremental cost effectiveness ratios in non-1 genotype
coinfected patients were considerably less than $40,000 per life year
saved.
Conclusions:
Treatment of chronic HCV
with pegylated interferon-alpha and ribavirin is
most cost-effective in
HIV-infected patients with CD4>500/mm3 and in those with nongenotype 1 HCV. For patients with genotype 1 HCV, the cost
effectiveness of HCV treatment is highly dependent upon treatment
efficacy. Our data suggest that
treatment of genotype 1 HCV in HIV coinfected patients may be reasonable.
Further clinical studies are
needed to assess the effects of treatment regimens in patients with different
stages of HIV and liver disease.
Abstract ID: 61982
Category: LO1: Public Policy, Epidemiology, and Decision Analysis
The role of liver biopsy for asymptomatic liver enzyme elevation.
M. Le
Mire, Royal Adelaide and Lyell McEwin Hospitals, Adelaide, Australia, K.
Fleming,
John Radcliffe Hospital, Oxford, United Kingdom (Great Britain), R.
Chapman,
John Radcliffe Hospital, Oxford, United Kingdom (Great Britain)
Introduction:
Liver biopsy findings in
patients with asymptomatic liver enzyme elevation vary considerably. In studies
of patients without serologic evidence for viral, autoimmune or metabolic liver
disease, cirrhosis rates between 3 and 16% are reported and there is
considerable variation in etiology. This has created difficulty in defining the
role of liver biopsy and evidence-based guidelines are lacking. The study
reviewed diagnoses, fibrosis scores and complications from liver biopsy for asymptomatic
liver enzyme elevation including selected patients with isolated gamma
glutamyltransferase (GGT) elevation.
Methods:
The records of consecutive
patients who underwent liver biopsy to investigate mild transaminase (£5´ULN)
or GGT elevation of any level were studied. Patients with suspected alcoholic
liver disease (ALD), drug-induced liver disease or risk factors for
non-alcoholic fatty liver disease (NAFLD) were included. Patients with symptoms
or sera diagnostic of hemochromatosis, a1-antitrypsin-deficiency related, viral
or autoimmune liver disease were excluded. The study included 102 patients who
were biopsied during the period from 1997-2001. The mean aspartate transaminase
was 53.4 +/-36.7 (N<42) and GGT was 227+/- 276 (N<60). ALD was diagnosed
in 26, fatty liver in 18, non-alcoholic steatohepatitis (NASH) in 18 and minor
or non-specific changes in 20 patients. Treatment or drug withdrawal was
possible for 10 patients including 4 with primary biliary cirrhosis, 2 with
drug-induced liver disease and 2 with primary sclerosing cholangitis. The
pre-biopsy diagnosis was changed in 16 out of 64 patients for whom it was
recorded. In 15 patients with isolated GGT elevation 6 had a diagnosis of NAFLD
and 6 ALD. Bridging fibrosis was found in 12 and cirrhosis in 9 patients.
Milder fibrosis was found in 46 patients (Ishak 1-2) and no fibrosis in 34
patients. Five out of 15 patients with isolated GGT elevation had bridging
fibrosis or cirrhosis. Fifty-eight patients underwent biopsy without and 40
with ultrasound guidance, 5 with CT guidance and 3 were by the transjugular
route.
Results:
Five out of 58 unguided
biopsies did not yield an adequate sample compared with 1 out of 40
ultrasound-guided biopsies. Three complications occurred, all with unguided biopsies,
including 1 bile leak, 1 hemorrhage and 1 readmission with pain.
Conclusions:
·
The incidence of altered
diagnosis or advanced fibrosis in this study supports the use of liver biopsy
in patients with asymptomatic liver enzyme elevation including selected
patients with isolated GGT elevation.
·
The reduced frequency of
complications or inadequate samples with ultrasound guidance supports the use
of ultrasound to assist liver biopsy.
·
Liver biopsy for
seronegative changed the diagnosis in 25% and defined treatable liver in 10%.
·
Bridging fibrosis or
cirrhosis was found in 21% of biopsies.
·
In selected patients with
GGT evaluation and alcoholic liver disease, bridging fibrosis or cirrhosis was
found.
·
A lower rate of inadequate
sampling occurred with ultrasound guided liver biopsy.
Abstract ID: 62181
Category: LO1: Public Policy, Epidemiology, and Decision Analysis
Psychosocial Factors in Liver Transplantation: How are U.S. Centers Evaluating Them.
R. C.
Anderson, Medical College of Wisconsin, Milwaukee, WI, C. P. Johnson, Medical
College
of Wisconsin, Milwaukee, WI, J. Franco, Medical College of Wisconsin,
Milwaukee, WI
Introduction:
The liver transplant waiting
list has grown disproportionately to the number of transplants performed at
developed and MELD has
prioritized patients based on objective criteria.At this time no
standardization of psychosocial factors in those being evaluated for transplant
exists. The purpose of this study is to determine if psychosocial factors are
considered by transplant centers prior to listing for liver transplantation.
Methods:
A questionnaire developed by
a psychologist experienced in evaluating transplant candidates and addressing 4
major areas (alcohol and drug use, compliance, psychiatric and psychological
issues and psychosocial support systems) was sent to 43
Results:
Twenty questionnaires were
completed and were available for interpretation. ALCOHOL, TOBACCO AND ILLICIT DRUG USE: All 20 centers required a
period of alcohol abstinence with 19/20 requiring at least 6 months and 1/20
requiring 12 months. 19/20 centers required participation in drug and alcohol
treatment while 1 did not.17/20 centers required marijuana abstinence while
3/20 did not. Random drug testing was performed by 19/20 centers with the
frequency ranging from every 6 weeks to on as needed basis. Tobacco cessation
was required by 12/20 centers.
COMPLIANCE: All 20 centers excluded patients
that did not adhere to medication regimens, medical appointments and the
inability to remain drug or alcohol free.
PSYCHIATRIC AND PSYCHOLOGICAL ISSUES:
17/20 centers required a psychiatric or psychological evaluation and all 17
included a mental health professional in the evaluation process. 5/20 centers
excluded patients with psychiatric or psychological disease with the most
common exclusionary criteria being active psychosis. 6/20 centers excluded
patients with illiteracy or decreased mental capacity.
PSYCHOSOCIAL SUPPORT: 15/20
centers excluded candidates without psychosocial support systems with most
mandating 1 full time caregiver or support person. 12/20 centers would consider
transplantation for incarcerated individuals,7/20 would not and 1/20 would
evaluate each case individually.
Conclusions:
·
Despite the absence of
mandated uniform criterion, transplant centers utilize similar standards when
evaluating liver transplant candidates for drug and alcohol abstinence, medical
compliance, psychiatric or psychological issues and psychosocial support
systems.
·
All centers required at
least 6 months abstinence from alcohol.
·
The majority of Centers
answering the survey required tobacco cessation.
·
The majority of centers will
not consider patients with significant psychiatric or psychological disease for
transplant.
·
Illiteracy remains a barrier for transplant in most Centers.
Abstract ID: 66511
Category: LO1: Public Policy, Epidemiology, and Decision Analysis
Real time ultrasound guided liver biopsy in real life; a comparison of pre-biopsy versus real time ultrasound.
S.
MANOLAKOPOULOS, Gastroenterology Department, ‘Polykliniki’ General
Hospital,
ATHENS, Greece, C. TRIANTOS, Gastroenterology Department,
‘Polykliniki’
General Hospital, ATHENS, Greece, S. BETHANIS, Gastroenterology
Department,
‘Polykliniki’ General Hospital, ATHENS, Greece, J. THODOROPOULOS,
2nd Gastroenterology
Department, ‘Evangelismos’ General Hospital, ATHENS, Greece,
J.
VLACHOGIANNAKOS, 2nd Gastroenterology Department, ‘Evangelismos’ General
Hospital,
ATHENS, Greece, E. CHOLONGITAS, Liver Transplantation and
Hepatobiliary
Unit, Royal Free Hospital, London, United Kingdom (Great Britain), M.
SIDERIDIS,
Radiology Department, 'Polykliniki' General Hospital, ATHENS, Greece,
K.
BARBATI, Histopathology Department, ‘Hellenic Red Cross’ General Hospital,
ATHENS,
Greece, P. PIPEROPOULOS, Radiology Department, ‘Evangelismos’
General
Hospital, ATHENS, Greece, C. SPILIADI, Histopathology Department,
‘Evangelismos'
General Hospital, ATHENS, Greece, N. PAPADIMITRIOU, 2nd
Gastroenterology
Department, ‘Evangelismos’ General Hospital, ATHENS, Greece, D.
TZOURMAKLIOTIS,
Gastroenterology Department, ‘Polykliniki’ General Hospital,
ATHENS,
Greece, A. BURROUGHS, Liver Transplantation and Hepatobiliary Unit,
Royal
Free Hospital, LONDON, United Kingdom (Great Britain), A. AVGERINOS, 2nd
Gastroenterology
Department, ‘Evangelismos’ General Hospital, ATHENS, Greece
Background:
Traditionally, liver biopsy
has been performed by hepatologists/ gastroenterologists. However, an
increasing number are performed by radiologists under ultrasound control.
Routine ultrasound assessment of puncture site before performing percutaneous
biopsy has been reported to increase diagnostic yield and decrease complication
rates. Liver biopsy guided by real time ultrasonography is a safe and effective
method for the
diagnosis of liver disease.
It is not clear if the latter is superior to marking the puncture site before
biopsy as regards biopsy size, fragmentation and complications.
Aim:
To compare ultrasound
assessment of the puncture site before performing percutaneous liver biopsy
with real time ultrasound liver biopsy for suspected diffuse liver disease
Patients/Methods:
From January 1995 to
September 2004, 558 percutaneous liver biopsies for diffuse liver disease were
performed. There were 2 groups: a) group A: real time u/s guided performed by
radiologists (213 biopsies, M/F=120/93, median age 50 yrs (range 17 -76),
needle 18G) b) group B: u/s assessment by radiologists of puncture site the
same day or within previous 24 hours of liver biopsy the (338 biopsies,
M/F:246/92, median age 43 yrs (range 15 -75), needle 16G). These biopsies were
performed by experienced
gastroenterologists/hepatologists
on the ward using the marked site.
Results:
There were no differences in
severity of liver disease nor length of specimen
(mean=1.43±0.59 group A vs
1.48±0.38 group B (p=0.39)) nor number of fragments (mean=1.41±0.75group A vs
1.38±0.87.group B (p=0.39)) nor number of passes. There was no difference in
establishing diagnosis (p=0.086). No diagnosis was reached in 7 in Group A (4
inadequate sample and 3 no liver tissue) and in 23 in group B (4 inadequate
sample and 19 no liver tissue). After using step-wise logistic regression two
independent
variables were statistically
significant for diagnosis: biopsy length (p=0.004) and fragment number
(p<0.001). One patient bled in Group B (required 2 units of blood
transfusion and no surgery).
Conclusion:
Real time ultrasound did not
improve diagnostic yield or result in less complications. Marking the puncture
site seems adequate and has practical advantage in employing less of the
radiologists time.
Abstract ID: 66908
Category: LO1: Public Policy, Epidemiology, and Decision Analysis
Inform Consent for Clinical Trials- Still some way to go.
a.
cheok, National University Hospital, singapore, AL, Singapore
Introduction:
Informed consent is the
process of giving participant all of the information
that participant needs to
make an decision about involvement in a research study. It is effective only if
patients understand the study information presented by the medical team.
Aim:
We set to determine
understanding of the informed consent process in Asian
patients with chronic
hepatitis B. Methods 77 Chinese patients with chronic hepatitis B from 12
randomized controlled clinical trials on nucleotide analogues were asked to
participate in this survey. All subjects had given informed consent at an
earlier date. They were interviewed on a 10-item questionnaire. To avoid bias,
the interview was conducted by one administrative assistant, who had not been
involved in any clinical trial
or informed consent process.
Data were expressed in mean ±S.D. In univariate analysis, Mann-Whitney U test
and Kruskal-Wallis test were used.
Results:
Age of subjects was 40.32
±12.07 (range 21-68) years, 66 (85.7%) were male. On a visual analogue scale of
1(minimum) to 5 (maximum), scores for comprehensiveness and complexity of the
consent form was 3.67 ± 0.82 and 2.56 ± 1.04 respectively, and score for their
understanding of informed consent was 3.84 . On the specific aspects of
clinical trials, only 22 (28.6%) subjects thought their trials were randomized
. Only 26 (33.8 %) knew placebo was a non-active drug and 20 (26.0%) patients
knew that their clinical symptoms might not due to the side effects of the study
drug. 76 (98.7%) felt benefited from trials: 65 (84.4%) felt they had better
medical attention, 45 (58.4%) patients felt benefited from the new drug, and 51
(66.2%) felt benefited from free treatment and blood tests. The concept of the
informed consent were summarized by given scores (0-4). The mean score of the
study group is 1.7 ±0.9. In univariate analysis, the differences of the score
were seen only in different education level (P=0.01) although different
aspects, such as race, religion, income level, marital status were tested.
Conclusion:
Despite the fact that all
subjects in this study gave an earlier informed consent for the respective
clinical trials, many had an incorrect idea and impression about the meaning of
placebo, randomization, and the follow up procedures of a clinical trial. More
time is needed to explain to patients
with lower education level.
Further education and streamlining of the informed consent process may be
needed for patients from Asia.
Abstract ID: 68207
Category: LO1: Public Policy, Epidemiology, and Decision Analysis
METHODOLOGICAL ISSUES IN COST EFFECTIVENESS EVALUATION OF HEPATITIS A VACCINE: A SYSTEMATIC REVIEW
A. M.
Anonychuk, University Health Network, Department of Medicine, Toronto, ON,
Canad,
Toronto, Canada, A. Tricco, GlaxoSmithKline Canada, Biomedical Data
Science,
Oakville, ON, Canada, Oakville, Canada, C. Bauch, University of Guelph,
Mathematics
and Statistics, Guelph, ON, Canada, Guelph, Canada, B. Pham,
GlaxoSmithKline
Canada, Biomedical Data Science, Oakville, ON, Canada, Oakville,
Canada,
M. Krahn, University Health Network, Department of Medicine, Toronto, ON,
Canad,
Toronto, Canada
Purpose:
Current policy regarding
hepatitis A (HA) vaccination in high-endemicity
regions and among high-risk
groups is influenced by published cost-effectiveness analyses (CEA); however
results of these vary widely across studies. A systematic review was conducted
to estimate the effects of methodologic quality. Adequate representation of
vaccine-induced herd-immunity and accurate estimation of the degree of
underreporting were assessed.
Methods:
CEA studies of HA vaccine
were identified (MEDLINE, EMBASE, and two
others; MeSH
“cost-effectiveness” AND “hepatitis A”), and included if they were
costeffectiveness/ utility studies of HA vaccine. Citations and full-text
articles were reviewed independently by two reviewers. Back referencing, author
searches, and expert consultation ensured literature saturation. Quality of
reporting was assessed using a 21-item quality tool (Neumann 2000).
Methodological issues specific to vaccine evaluations were appraised by Beutels
2002 guideline. Key modeling issues were examined using Sculpher’s 2000
framework.
Results:
34 CEA studies were included
from full-text-article review (n=95) and citation screening (n=700). 9
conducted an additional cost-utility analysis (CUA) and 6 a cost benefit
analysis. All were model-based studies, 13 utilizing Markov models. 1 used a
dynamic model, capturing effects of herd immunity. Strategies included mass
childhood/adult (n=11/n=2) and selective childhood/adult vaccination
(n=24/n=8). Populations assessed were healthy participants (n=31), and patients
with chronic liver disease (n=3).
The median score on the
21-item tool was 62% (13/21 range[14-90%]) similar to mean scores (58%) of
other CEA. CUA (n=9) attained higher quality (median 76%[57-90%]) than CEA
(n=25, 52%[14-71%]).
CUA studies assessed using
Beutels guideline clearly stated model assumptions (7/9), utilized proper time
span (7/9), and captured relevant costs (7/9). Many did not discuss alternative
modeling approaches (7/9).
Using Sculpher’s framework,
CUA studies specified model assumptions (9/9), and most justified model
parameters (7/9). Some did not discuss implications of relaxing model
assumptions (3/9). None adjusted for herd immunity, though 4 acknowledged this
as a limitation. 1 study adjusted for under-reporting, though 5 studies
discussed it.
Discussion:
·
On average, studies that
conducted a cost-utility analysis seemed to attain a higher quality of
reporting than CEA only studies.
·
Herd immunity effects were
not accounted for in most CEA studies.
·
Most CEA studies did not
account for under-reporting in HA case-notification data when used as input in
the analysis.
·
Large variation was evident
in the methods used in these studies. This potentially relates to the large
discordant results reported from these studies.
- The relative efficiency of HA vaccination programs evaluated in these studies were likely to be sensitive to uncertainty in HA incidence, vaccine costs and discount rates.