Hepatitis G virus infection in a high-risk subgroup of

hospitalized dental patients

Yutaka Takata, MD, PhD,a Akira Tateishi, DDS, PhD,b Hideo Kurokawa, DDS, PhD,c Megumi
Fujikawa, MD,a Kiyoshi Matsumura, MD,a Masanori Wakisaka, MD,a Jinichi Fukuda, DDS,
PhD,b and Minoru Kajiyama, DDS, PhD,c Kitakyushu, Japan
KYUSHU DENTAL COLLEGE

Objective. The prevalence of hepatitis G virus infection was evaluated in dental patients whose clinical laboratory test results were
positive for hepatitis C virus antibody, hepatitis B virus surface antigen, or elevated serum alanine transaminase concentrations.
Study design. Frozen serum samples from patients with hepatitis C virus antibody (n = 63), hepatitis B virus surface antigen (n
= 20), or alanine transaminase concentrations greater than 100 IU (n = 14) were assessed for GB virus C (GBV-C)/hepatitis G
virus RNA by a reverse transcriptase-polymerase chain reaction.
Results. Six of 63 patients with hepatitis C virus antibodies had serum hepatitis G virus RNA (9.5%), and 2 of 20 subjects with
hepatitis B virus surface antigen had hepatitis G virus RNA (10.0%). None of 14 patients whose alanine transaminase concen-
tration was greater than 100 IU/L had hepatitis G virus RNA. Of 4 subjects with both hepatitis C virus antibody and hepatitis B
virus surface antigen, 2 had hepatitis G virus RNA (50%). In the total study population (N = 92), 6 subjects (6.5%) had
hepatitis G virus RNA. All hepatitis G virus–infected patients also had hepatitis C virus antibody. Neither serum alanine
transaminase nor aspartate transaminase concentrations were different between subjects with and subjects without hepatitis G
virus RNA. The lack of a relationship between hepatitis G virus infection and elevation of alanine transaminase and aspartate
transaminase might suggest that this virus is not truly a hepatitis virus.
Conclusions. Hospitalized dental patients are infected with hepatitis G virus at a prevalence similar to or slightly higher than
that seen in the general population. Dentists should pay close attention to infection control with respect to the potential new
hepatitis virus known as hepatitis G virus.
(Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:442-5)

Hepatitis B virus (HBV) and hepatitis C virus (HCV)
are responsible for most cases of bloodborne hepatitis.
Although transmission of HBV and HCV is mainly by
way of blood and blood products,1 saliva also may be a
source of infection with HBV2,3 and HCV.4,5 Hepatitis
G virus (HGV),6-9 a recently identified non–A-through-
E hepatitis-associated RNA virus of the flaviviridae
family,7 is distinct from hepatitis A-through-E viruses
and is parenterally transmitted.8 The clinical manifesta-
tions of HGV infection are usually trivial, but in Japan
this virus has been associated with fulminant hepatitis
of unknown cause.10 Like HBV and HCV, HGV is
present in human saliva.11 Needlestick injury during
dental treatment may cause infection of dental
personnel by these viruses, although it is still possible
that needlesticks are not a route of transmission for
HGV. In our dental hospital,12 needlestick injuries have
occurred 35 times during the past 3 years; in these 35
instances, 8 patients were HCV-seropositive and 1
patient was positive for HBV surface antigen (HBs-Ag).
At present, the needlestick-induced transmission rate of
aDepartment of Internal Medicine.
bFirstDepartment of Oral Surgery.
cSecond Department of Oral Surgery.
Received for publication June 15, 1998; returned for revision Aug
15, 1998; accepted for publication Nov 16, 1998.
Copyright © 1999 by Mosby, Inc.
1079-2104/99/$8.00 + 0 7/13/96118
442
HCV and HBV in our dental college hospital is zero;
however, dentists have a higher prevalence of seroposi-
tivity for HBV and HCV than control populations, indi-
cating a high occupational risk for HBV13,14 and HCV
infection.15,16 In particular, prevalence was reported to
be high among oral surgeons.13,14,17
One suspects that dentists may similarly be exposed
to HGV infection during dental treatment. The preva-
lence of HGV in the general population is 1.0% to
2.0%.9,18 HGV RNA has been detected in up to 4% of
blood donors (reported rates: 0.5%,19 0.8%,20 2%,21,22
3%,23 and 4%24), and the prevalence is much higher in
patients with elevated aminotransferase (13%),25 intra-
venous drug users (33%,23 43.2%26), patients with
chronic hepatitis C (11%,27 27%28), chronic hemodial-
ysis patients (6%,29 16%30), and blood transfusion
recipients.20,29
For the protection of dentists from HGV, precise
knowledge of the prevalence of virus carriers among
dental patients is essential. Shopper et al,31 studying
the prevalence of HCV in a sample of dental school
outpatients, showed that more than 5% of these
patients were seropositive for anti-HCV, a rate higher
than that seen in the general population. We also found
a relatively high prevalence of HCV seropositivity in
our dental college hospital.32 The prevalence of HGV
infection could also be higher in dental patients than in
the general population.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
Volume 87, Number 4
In this study, the prevalence of HGV infection in
hospitalized dental patients who were positive for HCV
antibody or HBs-Ag or showed a high serum alanine
transaminase (ALT) level was evaluated.
PATIENTS AND METHODS
Subjects included 1923 consecutive dental patients
(male, 1010; female, 913) hospitalized from January
1994 to December 1996 at the First and Second
Divisions of Oral Surgery, Kyushu Dental College
Hospital, Kitakyushu, Japan. The average age of this
population was 41.0 ± 0.5 years; the age range was
from less than 1 year to 97 years. The study was
approved by the Human Investigations Committee of
Kyushu Dental College. The dental diagnosis leading
to hospitalization was inflammation in 665 cases, cyst
in 282, cancer in 241, trauma in 210, impacted teeth in
194, benign tumor in 126, anomalies in 114, and
sialolithiasis in 28; various other diagnoses were seen
in 63 cases. The prevalence of patients with HBs-Ag
was 26/1455 (1.8%), and the prevalence of patients
with HCV antibody was 91/1436 (6.3%).
After storage at –20°C, serum samples from patients
with HCV antibody (n = 63; in the other 28 subjects
with HCV antibody, samples were not taken or there
was insufficient volume for examination of HGV
RNA), patients with HBs-Ag (n = 20), and patients
with serum ALT levels higher than 100 IU/L (n = 14)
were used in studies designed to identify GB virus C
(GBV-C)/HGV RNA. GBV-C/HGV RNA was detected
by reverse transcriptase-polymerase chain reaction
(RT-PCR).23 The 3' untranslated region (UTR) was
adopted as the primer for HGV RNA assay in the
present study because this region was well conserved
in comparison with the 5' UTR region (Okamoto et
al33), which is used as the primer in the technique of
Schlueter et al.23 A positive control and a negative
control were used for each assay; Southern blot was not
used to confirm the product. In contrast to the speci-
ficity and sensitivity attained with the method of
Schlueter et al,23 the specificity of our method was
99.7% to 100% and its sensitivity was 100% (n = 322).
HCV RNA was measured according to the methods
of Shiratori et al,34 in which primer sequences were
chosen from the 5' end noncoding region of the HCV
genome (upstream primer KY80, nt 56-79; down-
stream primer KY78, nt 276-299). A positive control
and a negative control were used for each assay;
Southern blot was not used to confirm the product. In
contrast to the specificity and sensitivity attained with
the standard method of RT-nested-PCR, the specificity
of our method for HCV RNA was 100% and its sensi-
tivity was 93.5% (n = 89).
The total number of sera used for assay of HGV RNA
was 92, inasmuch as some patients had evidence for
Takata et al 443
Fig 1. Prevalence of HGV RNA in sera from subjects with
HCV antibody, HBs-Ag, HCV antibody + HBs-Ag, ALT
(>100 IU/L), HCV RNA, or no HCV RNA, and from all
subjects. Numbers of subjects are shown in parentheses.
both HBV and HCV. This group of 92 subjects whose
HGV RNA was examined consisted of 28 patients with
chronic hepatitis C, 9 patients with chronic hepatitis B,
13 patients with chronic liver disease, 2 patients with
fatty liver disease, 1 patient with both chronic hepatitis
B and chronic hepatitis C, 1 patient with alcoholic liver
disease, and 38 subjects without liver disease. No
patients with periodic hemodialysis, intravenous drug
user patients, or persons with tatoos were included. Ten
patients had histories of blood transfusion. From none
of the patients did we have a history accurate enough to
indicate whether the patient was undergoing treatment
for liver disease. All patients were ambulatory. We had
no information on when any patient’s last dental
appointment had been. Sera from 63 of the 92 subjects
were assayed for HCV RNA by RT-PCR. All data are
presented in the form mean ± SEM. Differences were
examined with the unpaired Student t test where appro-
priate, and categoric variables were compared through
use of the chi-square test or the Fisher exact probability
test. Results were considered to be significant when the
P value was less than .05.
RESULTS
Six of the 63 patients with HCV antibody had HGV
RNA in their sera (9.5%), and 2 of the 20 subjects with
HBs-Ag had HGV RNA (10.0%; Fig 1). The preva-
lence of HGV infection was similar between subjects
with HCV antibody and subjects with HBs-Ag (DF = 1,
χ2 = 0.01, P > .05). None of the 14 patients whose ALT
concentration was greater than 100 IU/L had HGV
RNA, but this prevalence was not significantly lower
than in subjects with HCV antibody or HBs-Ag (DF =
444 Takata et al
2, χ2 = 1.35, P > .05). Of 4 patients with both HCV
antibody and HBs-Ag, 2 had HGV RNA (50%), but
this prevalence was not significantly greater than in
other groups (DF = 3, χ2 = 5.67, P > .05). One patient
with HBs-Ag also had a serum ALT concentration
higher than 100 IU/L; his serum tested negative for
HGV RNA. For the 63 subjects whose serum was
measured for HCV RNA, RT-PCR was positive in 33
samples and negative in 30 samples. Four subjects
were found to be infected with HGV among 33 HCV
RNA–positive patients (12.1%), and 2 subjects were
infected with HGV among 30 HCV RNA–negative
patients (6.7%; DF = 1, χ2 = 0.45, P > .05). Of 92
subjects, 6 had HGV RNA. All HGV-infected patients
also had HCV antibody. The prevalence of HGV infec-
tion was 6.5% for the 92 patients.
With respect to dental diseases in the group of 6
patients with HGV RNA, there were 2 cases of bone
fracture, 2 cases of periostitis, 1 case of impacted teeth,
and 1 case of external dental fistula. The average age
for the HGV-positive patients was 37.8 years; the male-
female ratio was 4:2. None of these patients had a
history of drug abuse, homosexuality, hemophilia,
blood transfusion, or hemodialysis. Neither serum ALT
nor serum aspartate transaminase (AST) concentra-
tions were significantly different between subjects with
and subjects without HGV RNA (ALT, 31.3 ± 5.3 IU/L
for HGV RNA-positive, 48.2 ± 6.7 IU/L for HGV
RNA-negative, t = 1.98; AST, 26.7 ± 4.0 IU/L for HGV
RNA-positive, 43.7 ± 7.8 IU/L for HGV RNA-nega-
tive, t = 1.95). Serum gamma glutamyl transpeptidase
was significantly elevated in subjects without HGV
RNA (47.1 ± 6.7 IU) in comparison with subjects with
HGV RNA (19.4 ± 5.4 IU, t = 2.55, P < .05).
DISCUSSION
In the present survey of dental inpatients believed to be
at increased risk for HGV, serum HGV RNA was
detected in 6 of 63 patients with HCV antibody (9.5%)
and in 2 of 20 subjects with HBs-Ag (10.0%). Our results
showed that dental patients with HBV or HCV frequently
have HGV, at a prevalence similar to that seen in
nondental subjects with HBV20,35 or HCV.20,27,28,35,36
Nagao et al37 reported recently that GBV-C RNA was
detectable in 1 oral cancer patient (2.6%) and in 3
patients with oral lichen planus (8.8%), and these 4 GBV-
C–positive patients were also positive for HCV antibody.
Similarly, HGV-positive persons were always HCV-posi-
tive in our study. A slight excess, not statistically signifi-
cant, was seen in the prevalence of HGV in patients with
HCV RNA in comparison with patients without HCV
RNA, possibly suggesting that active infection with
HCV, as opposed to a history of HCV infection, may be
related to HGV viremia. HGV is present in saliva11 and
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
April 1999
can be transmitted by saliva as well as by blood.1 These
observations should spur dentists to address the problems
of infection control concerning the potential new
hepatitis virus, HGV. Of 4 subjects with both HCV anti-
body and HBs-Ag, 2 had HGV RNA (50%), a fact that
suggests a higher incidence of HGV positivity in subjects
doubly infected with HBV and HCV.
None of 14 patients with high ALT concentrations in
the present study had HGV RNA. Although HGV has
been suspected of having pathogenic significance in
non–A-through-E hepatitis,9,18 the prevalence of HGV
infection is not uniformly high among patients with
chronic non–A-through-E hepatitis.19,20,38 Some inves-
tigators have found an increased prevalence of HGV
infection in subjects with elevated aminotransferase
concentrations.25,35 These findings, taken together with
our results, suggest that whether HGV is responsible
for causing non–A-through-E hepatitis remains to be
determined. Serum ALT and AST concentrations did
not differ between our subjects with and our subjects
without HGV RNA, and serum gamma glutamyl
transpeptidase was elevated slightly in subjects without
HGV RNA in comparison with subjects with HGV
RNA—another fact that casts doubt on the clinical
significance of HGV as an agent causing hepatitis.
The prevalence of HGV infection in our 92 selected
dental inpatients was 6.5%, which is higher than the
prevalence seen in the general population9,18 and
higher than that seen in blood donors,19-24 probably
because we selected subjects infected with HBV or
HCV, whose prevalences of HGV infection are known
to be higher than usual.20,27,28 Our results are not repre-
sentative of dental patients in general.
Piazza et al39 showed extensive contamination by
HCV of dental equipment after treatment of patients
with HCV. Because HGV is present in some dental
patients and can be transmitted in a fashion similar to
that seen in HBV and HCV, risks may be significant for
the transmission of HGV, as well as these other viruses,
to other dental patients if sterilization and disinfection
are inadequate. Furthermore, even perfect sterilization
and disinfection of dental instruments cannot prevent
dental workers from being infected with HGV by acci-
dental needlestick injuries during treatment, although
HGV has not been proved to be associated with a
significant risk of transmission in the dental office or
by needlestick injuries. Exercising care to avoid such
injuries is the most important and effective measure
that can be taken to prevent this transmission.
In conclusion, 6.5% of hospitalized dental patients
with liver abnormalities were found to be infected with
HGV. The prevalence of HGV among hospitalized
dental patients may be similar to or slightly higher than
that seen in the general population.
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
Volume 87, Number 4
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Reprint requests:
Yutaka Takata, MD, PhD
Department of Internal Medicine
Kyushu Dental College
Manazuru 2-6-1, Kokurakita-ku
Kitakyushu City, 803-8580
Japan