Rheumatology 1999;38:1279–1281
Prevalences of hepatitis A, B, C and E viruses
in Behçet’s disease
K. Aksu, Y. Kabasakal, A. Sayıner1, G. Keser, F. Oksel, A. Bilgiç1,
G. Gümüşdiş and E. Doǧanavşargil
Division of Rheumatology, Department of Internal Medicine and 1Clinical
Microbiology, Ege University School of Medicine, Bornova, İzmir, Turkey
Abstract
Objective. To determine whether Behçet’s disease (BD), being a systemic vasculitis of
unknown aetiology, is associated with hepatitis viruses (HAV, HBV, HCV and HEV ).
Methods. In addition to 124 patients [male:female (M/F ): 73/51], all fulfilling the diagnostic
criteria of the International Study Group for BD (1991), 14 patients with systemic necrotizing
vasculitis (M/F: 7/7), 47 patients with ankylosing spondylitis (M/F: 36/11) and 51 healthy
controls (M/F: 22/29) were also included in this study. Serological markers of four different
types of hepatitis (anti-HAV IgM, total anti-HAV, HBsAg, anti-HBs, total anti-HBc,
anti-HBc IgM, anti-HCV and anti-HEV ) were studied in all cases.
Results. There was no difference between the groups with respect to HAV, HCV and HEV
serologies. Anti-HBs positivity was observed less frequently in BD compared with healthy
controls and systemic vasculitis (P < 0.05).
Conclusion. Serological evidence of previous HAV, HCV and HEV infections was not
significantly different between Behçet’s patients and other groups. However, previous HBV
infection was found in a significantly lower number of BD patients as compared with healthy
controls and systemic vasculitic patients.
K : Behçet’s disease, Hepatitis A virus (HAV ), Hepatitis B virus (HBV ), Hepatitis C
virus (HCV ), Hepatitis E virus (HEV ), Prevalence.
Behçet’s disease (BD) is accepted as a vasculitis of
unknown aetiology that affects vessels of different type,
size and localization, and with exacerbation and remission periods. It is well known that some microorganisms,
especially viruses, can be a triggering factor via soluble
immune complexes in vasculitic diseases. In this respect,
some hepatitis viruses are associated with vasculitis. As
an example, an important percentage of polyarteritis
nodosa patients have a history of previous hepatitis B
(HBV ) infection [1]. The rate of mixed cryoglobulinaemia is increased in patients with hepatitis C virus
(HCV )-related chronic liver disease and in HCV carriers
[2]. Until today, in BD, only the association with HCV
has been investigated and no such relationship has
been found.
In this study, we aimed to determine the prevalence
of hepatitis A (HAV ), B, C and E (HEV ) viruses in BD.
Materials and methods
In this cross-sectional and descriptive study, medical
records of 137 Behçet’s patients who applied to the
Ege University rheumatology out-patient department
between May 1996 and November 1998, meeting the
Submitted 24 February 1999; revised version accepted 4 June 1999.
Correspondence to: K. Aksu, 80 Sokak No: 27/3, 35040 Bornova,
İzmir, Turkey.
criteria of the International Behçet’s Disease Study
Group, were evaluated. All these patients were invited
by mail to participate in our study. Those refusing to
take part in this study or who had a history of hepatitis
A or B vaccination, blood transfusion and/or drug abuse
were excluded from the study. A total of 124 Behçet’s
patients eligible for our study [male/female (M/F ):
73/51)] were studied. Fourteen patients with systemic
vasculitis (SV ) (M/F: 7/7) and 51 healthy controls
(M/F: 22/29) were also included. Since BD was accepted
as a spondyloarthropathy by some authors, 47 patients
with ankylosing spondylitis (AS) (M/F: 36/11) were
also included in the control group. The healthy control
group was selected from age-compatible blood donors.
Hospital staff were not included in healthy controls. We
excluded patients with drug abuse, hepatitis A or B
vaccination history and previous blood transfusion from
our healthy controls.
Sera were tested for total anti-HAV, anti-HAV IgM
(AXSYM System, Abbott Diagnostics, USA), HbsAg,
anti-HBc IgM and total anti-Hbc, anti-HBs (Organon
Teknika, The Netherlands), anti-HCV ( UBI, III generation, United Biomedical Inc., USA) and anti-HEV
(Abbott Diagnostics, USA) antibodies. Sera were also
tested for HCV antibodies by third-generation line
immunoassay (LiaTek, HCV III, Organon Teknika, The
Netherlands) when results of the enzyme immunoassay
were positive. HCV RNA was tested by reverse tran-
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© 1999 British Society for Rheumatology
K. Aksu et al.
1280
scription-polymerase chain reaction (RT-PCR) (Cobas
Amplicor, Roche Diagnostic Systems, USA) in antibody-positive patients.
The data were evaluated under SPSSWIN by Mann–
Whitney U, Wilcoxon, Fisher’s exact test and Pearson
analyses using a two-sided P value of <0.05 as the level
of significance.
Results
There was no significant difference between Behçet’s,
AS patients and healthy controls with respect to age
and sex. However, since SV is seen in a considerably
higher age group, the mean age of this group was
significantly higher than that of the other three groups.
Demographic features of the patients are shown in
Table 1.
Serological evidence of previous HAV, HBV and HEV
infections was found to be positive in 117 (94%), 39
(31%) and 9 (7%) patients with BD, respectively
( Table 2). In this group of patients, HBsAg positivity
was 4% (5/124). One patient was diagnosed as having
acute HAV infection. An episode of venous thrombosis
was documented in 27% (34/124) of Behçet’s patients,
but no significant association was found between these
patients and the other subjects with respect to the
serological markers studied. Anti-HCV antibodies were
found in one case only (0.8%), which was confirmed by
line immunoassay test. HCV RNA was negative in this
patient. The frequency of HCV antibody positivity in
BD patients was not significantly different than in the
SV groups.
Serological findings indicated previous HAV infection
in 93% (13/14) and HBV infection in 57% (8/14) of the
patients with SV. Anti-HBs positivity was significantly
increased in the SV group when compared with Behçet’s
(P = 0.0219) and AS patients (P = 0.0098). There was
no significant difference in the anti-HBs positivity
between patients with SV and healthy controls. None
of the patients with SV were HBsAg carriers or antiHEV positive. Even though there was only one patient
with anti-HCV positivity in the SV group, the difference
was not significant when compared with BD patients
(P > 0.05).
In the AS group, 95% (45/47) anti-HAV, 2% (1/47)
anti-HEV, 23% (11/47) anti-HBc and anti-HBs positivity were found. Only one patient in this group was an
HbsAg carrier, while no HCV positivity was detected.
In the healthy control group, the rate of previous
HAV infection was 93% and HBV infection was 47%.
Anti-HEV positivity was detected in 8% of the subjects.
There were 4% HBsAg carriers and none with anti-HCV
positivity. The rate of previous HBV infection was
significantly lower with respect to the control group,
BD (P = 0.0428) and AS groups (P = 0.0211). No significant difference was found between the BD patients
and the other study groups regarding HAV, HCV and
HEV prevalences.
Discussion
In the literature, we could find only two studies investigating the relationship of BD and HCV infection. In the
first study, Hamuryudan et al. [3] found no anti-HCV
positivity among 13 BD patients with arterial and pulmonary aneurysms. In the second study, performed by
Oǧuz et al. [4], anti-HCV positivity was detected in only
one in 224 patients with BD. Being consistent with these
previous studies, anti-HCV positivity in our study was
also one in 124 BD patients (0.8%) and this frequency
was not significantly different from other groups, including normal controls. In an epidemiological study investigating anti-HCV prevalence in a Turkish population,
anti-HCV positivity was found to be between 0.3 and
1.8% among blood donors and healthy subjects [5].
On the other hand, we could find no study in the
literature regarding the relationship of BD with HAV,
HBV and HEV. HBV infection has been well known to
contribute to the aetiopathogenesis of SV. Anti-HBs
positivity, as evidence of previous HBV infection, was
significantly higher in our SV group than the BD group.
Since the mean age in the SV group was higher than in
T 1. Demographic features of cases
BD
Number of cases
Female/male
Mean age
Mean disease period (months)
Systemic vasculitis
124
51/73
34 ± 9 (16–61)
63 ± 62
14
7/7
51 ± 16 (23–76)
6 ± 19
Healthy controls
51
29/22
35 ± 13 (15–65)
–
AS
47
11/36
37 ± 12 (16–69)
111 ± 103
T 2. Hepatitis serologies of all groups
HBV
BD
AS
SV
Healthy controls
HAV
Total anti-HAV
positivity (%)
Anti-HBs
positivity (%)
HbsAg
positivity (%)
HCV
Anti-HCV
positivity (%)
HEV
Total anti-HEV
positivity (%)
94
95
93
93
31
23
57
47
4
2
–
4
0.8
–
7
–
7
2
–
8
Behçet’s disease and hepatitis viruses
the other three groups, these patients may have been
exposed to HBV more frequently, which might explain
their higher anti-HBs positivity rate.
Several epidemiological studies performed in different
parts of Turkey have reported anti-HBs prevalence to
range between 20.6 and 56.3%, and the rate of the
HBsAg carrier state to range between 3.9 and 12.5%
[5]. Unfortunately, there was no study performed to
search for the prevalence of anti-HBs positivity in İzmir
and the central Aegean of Turkey, where the patient
population of our study was living. Being a unique SV,
BD may also be expected to have a significantly higher
frequency of HBsAg positivity, compared with normal
controls. However, this was not the case in our study.
Since ethnic differences are considerably higher in
different parts of Turkey, this might have affected our
results. Remembering the anti-HBs positivity rates in
different regions of Turkey, the anti-HBs positivity rate
of our healthy controls (47%), which is actually higher
than that of our Behçet’s group, is not unacceptably
high.
The reason why anti-HBs positivity in BD and AS
was lower than in healthy controls can be speculated on
in two ways. Thirty-two out of 85 patients with antiHbs-negative BD had been receiving azathioprine treatment (2 mg/kg/day), as well as moderate doses of
prednisolone (0.25–0.5 mg/kg/day). There were even
some patients receiving pulse cyclophosphamide treatment. Since immunosuppressive treatment interferes
with humoral immunity, this might well contribute to
the reduction in titres of antibodies against HBsAg in
patients with BD.
One of the mechanisms of transmission of HBV
infection is sexual. Eighty-six per cent (n = 106) of our
patients with BD had recurrent genital ulceration.
Genital ulceration might well prevent these patients
from having frequent sexual intercourse.
HAV and HEV are both transmitted by the
faecal–oral route. HEV can cause fulminant hepatitis in
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the course of pregnancy, but none of the patients were
pregnant during the study. In Turkey, seroprevalences
of HAV and HEV in adults were reported to be 90 and
6%, respectively [6 ]. Similar rates have also been found
in our study. Regarding positive HAV and HEV serology, there was no significant difference between BD and
all the other groups, including healthy controls.
In conclusion, seroprevalences of HAV, HCV and
HEV infections were not significantly different between
Behçet’s patients and other groups including healthy
controls. While there was no significant difference between
Behçet’s patients and other groups with respect to
HBsAg positivity, anti-HBs positivity in Behçet’s
patients was significantly lower than in the SV group.
We may conclude that, despite the well-known role of
hepatitis viruses in SV, BD does not seem to be related
to these viruses.
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