Seroprevalence of anti-HCV Ab among Iranian hemophilia patients

Abstract

Due to their regular consumption of blood products, hemophiliacs are at greater risk for all forms of viral hepatitis, especially hepatitis C, than other patients. As yet, there is no vaccine available to prevent hepatitis C, and treatment of infected patients remains a problem. In this study, we have carried out a survey of the prevalence of hepatitis C infection and its risk factors among a group of hemophilia patients in Iran.

Full text

SEROPREVALENCE
OF
ANTI-HCV AMONG
IRANIAN
HEMOPHILIA
PATIENTS
Alavian SM, Ardeshir
A,
Hajarizadeh
B,
Tehran, Iran
INTRODUCTION
Due to their regular consumption
of
blood products,
hemophiliacs are at greater risk for all forms
of
viral hepatitis,
especially hepatitis C, than other patients. As yet, there is no
vaccine available to prevent hepatitis
C,
and treatment
of
infected patients remains a problem. In this study, we have
carried out a survey
of
the prevalence
of
hepatitis C infection
and its risk factors among a group
of
hemophilia patients in
Iran.
MATERIALS
AND
METHODS
A cross sectional study,
of
almost all hemophilia patients
referred to the "Iranian Hemophilia Society" between March
2000 and March 2001 was carried out. Demographic and
clinical data were obtained from patients and their serum
samples were tested. The sero-prevalence
of
antibodies against
hepatitis C virus (anti-HCV Ab) was determined by enzyme
linked immunosorbant assay (ELISA second generation).
Repeatably positive samples were further tested by
recombinant immunoblot assays (RIB A second generation).
Tests for HBs Ag, HBs Ab and HIV antibody were also carried
out on all samples.
RESULTS
We
enrolled 176 patients in this study; 152 (86.4%) were male
and 24 (13.6%) female. The mean age was 20.65 (±1O.45). 106
cases (60.2%) were anti-HCV positive. There was no
significant correlation between sero-positivity for anti-HCV
and gender, age, marital status, type or severity
of
the bleeding
disorder, type, volume or duration
of
blood products
consumed, and family history
of
hepatitis or anti-HCV sero-
status
of
mother and spouse, in our patients. Also, there was no
significant relation between anti-HCV sero-positivity and HBs
Ag sero-positivity in patients, although the sero-prevalence
of
HCV Ab was significantly higher in HBs Ab positive patients,
compared with HBs Ab negatives (P=0.038). Four patients
were HIV Ab positive, and all
of
them were positive for anti-
HCV
as
well.
DISCUSSION
AND
CONCLUSIONS
During the last decade, there have been published several cross
sectional studies
of
the prevalence
of
hepatitis C among
hemophilia patients, indicating a wide range from 25% to
100% [1-19]. This disparity must be due to a variety
of
reasons, such as: the difference in prevalence among general
populations
of
various countries; the anti-HCV detection
methods employed, or indeed whether or not donor screening
tests were carried out at all; and virucidal techniques applied to
the coagulation factor concentrates. The prevalence
of
hepatitis
C in the blood donor population in Iran is 0.12%, based on an
unpublished survey. In the light
of
this observation, anti-HCV
prevalence among hemophilia patients based on our survey
(60.2%) is somewhat higher than reports from most other cross
sectional studies. There is even one study from Asia, where
HCV infection is notoriously widespread, reporting a relatively
lower prevalence [2-4]. On the other hand, other studies in
Asia, report a relatively higher prevalence [5,6]. A previous
study carried out on a similar cohort
of
patients by the Iranian
Hemophilia Society in 1997, reported a 77.5% anti-HCV
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TRANSFUSION TODAY #49 -December 2001
It
prevalence [7]. Even though it is difficult to compare
the)
figures obtained in this study 3 years ago (which may have
employed an earlier generation
of
ELISA tests), with our
current investigation, carried out 6 years after the introduction
of
anti-HCV donor screening throughout Iran, our results may
suggest a declining trend in prevalence
of
infection.
We
have not found any association between anti-HCV sero-
positivity and gender, marital status and age in our patients.
Although, the older hemophilia patients were obviously
exposed to HCV infection for a longer time compared with
younger patients.
It
seems that the prevalence
of
HCV should
therefore be higher in this group. Both our study and other
similar studies, did not find any significant relation between
age and anti-HCV sero-positivity [2, 8-10]. This suggests that
our younger patients run the same risk
of
infection
as
older
patients, and indicates that unfortunately the strategies
employed for preventing HCV transmission in hemophilia
patients within the past
15
years have been ineffective.
Patients with milder disease require fewer factor concentrates
than individuals with more severe hemophilia and seem to be
at lower risk for HCV infection. However, there was no
significant association between anti-HCV sero-positivity and
severity
of
hemophilia, in this study. Most
of
the other similar
studies confirm our finding [8, 9, I I], although, there are also
published reports with results differing from ours l12].
Some
of
the previous reported surveys have shown that the use
of
small pool cryoprecipitate is associated with a lower risk
of
HCV infection, compared with the use
of
commercial
concentrates [12-14]. This finding was not confirmed by our
study. In addition, there was no significant association between
the number
of
concentrates consumed and anti-HCY status.
We
did not find any significant association between the family
history for hepatitis or the anti-HCY status
of
their mother and
spouse and anti-HCV status
of
the patients themselves. Other
studies have reported similar findings [6,
15]
and have
underlined the importance
of
transfusion and contaminated
blood product usage
as
the main source
of
HCY transmission.
We
found a significantly higher anti-HCY sero-positivity
prevalence in the patients positive for HBs Ab (P=0.038). But,
there was no association between HBs Ag and anti-HCY sero-
positivity.
In a number
of
studies, the association between HIV Ab and
anti-HCV sero-positivity in hemophilia patients has been
emphasized [3, 16-I 9].
In
this survey, all 4 HIY Ab positive
individuals were anti-HCY sero-positive as well, but no
significant association between these two variables was found.
This is presumably due to the relative rarity
of
HIV Ab positive
cases in the patient population we surveyed.
Transmission
of
HCV via blood products has been a significant
source
of
hepatitis C infection for patients with hemophilia, in
the past. Fortunately, a number
of
effective strategies,
including donor selection and screening and especially viral
inactivation procedures and more recently the use
of
recombinant factor therapy, have now been implemented in
order to prevent such transmissions.
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Correspondence:
Iranian Blood Transfusion Organization
Tehran Hepatitis Center
Dr. Seyed
Mo'ayed
Alavian
P.O.Box 14155/3651, Tehran, Iran
E-mail: sm_alavian@yahoo.com
sm_alavian@alavian-thc.org
•
ABSTRACT
IRAN
THE
IN
VITRO
ASSESSMENT
OF
TNF
PRODUCTION
ACCOMPANYING ABO & RHD
INCOMPATIBILITIES
Kadkhoda
K.,
Pourfathollah AA., Moazzeni
SM
Department
of
Immunology, Tarbiat Modarres University,
Tehran,
IRAN
Despite great advances in the field
of
Immunohaematology,
and the application
of
the principles
of
Quality Assurance in
blood transfusion practice in the course
of
the past decade,
numerous reports continue to be published,
of
adverse
haemolytic reactions following transfusion, due to human error
such as mislabeling. In some cases, these errors have led to
death.
Since the clinical manifestations
of
such reactions are very
similar to Septic Shock Syndrome, and in that Tumour
Necrosis Factor(TNF) plays a key part in this syndrome,
investigators have explored the role
of
cytokines such as II-I
alpha,
11-8
and
MCP-l,
as well as TNF, in adverse transfusion
reactions(l,2,3). Changes have been reported in the phenotypic
features
of
monocytes and neutrophils
of
patients suffering
these complications, and a few studies have been carried out to
examine the underlying mechanisms responsible for the
production and secretion
of
mediators such as
TNF
and other
cytokines. Davenport et
a1.(4)
reported huge
TNF
production
in ABO incompatibility, resulting from complement activation
accompanying A or B blood group antigen/antibody reactions,
when ABO incompatible whole blood samples are mixed in
vitro. He also reported on
TNF
production subsequent to RhO
incompatibility conditions
created in vitro, in which a blood monocyte monolayer was
exposed to red cells(rbcs) sensitised with IgG anti-RhO
antibodies. Davenport(5,6) postulated that IgG present on the
surface
of
rbcs may cross-link the Fc-gamma receptors on
monocytes, and that this might provide the signal leading to
TNF
secretion. Alternatively, the phagocytosis
of
rbcs by
monocytes may, in itself, provoke
TNF
production.
In the present study, we have tried to replicate these models
of
ABO and RhO incompatibility, and to establish identical
in
vitro conditions, in an attempt to confirm earlier reports, and to
unravel their findings.
To exclude interfering factors such as complement, whole
blood was washed three times with phosphate-buffered
saline(PBS) at pH 7.4, in order to eliminate complement
components from the medium. Two models were designed: an
IgM and IgG model for ABO and Rh incompatibilities
respectively. In the IgM model, anti-A sensitised rbcs, and in
the IgG model, anti-RhO sensitised rbcs were exposed to a
monocyte monolayer. Both models generated TNF production:
40,960 U/ml in the IgM model, and 1,280 U/ml in the IgG
model. The level
of
TNF
produced in the IgM model was
significantly (p<0.05) greater than that
of
the IgG model. The
TNF
secretion was measured using a murine fibroblast cell
line, L929.
Since complement had been eliminated from the culture
medium, an alternative mechanism is likely to have been
involved in the
TNF
production. There have been some reports
of
the
presence
of
Fc-mu
receptors
for
IgM
on
the
surface
of
monocytes(7,8). We therefore concluded that two probable
mechanisms were likely to have been involved in fostering
increased levels
of
TNF
in the culture supernatant. The first
tit
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