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Previous Article | Next Article 
Journal of Clinical Microbiology, January 1998, p. 110-114, Vol. 36, No. 1
0095-1137/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Past and Present Hepatitis G Virus Infections in
Areas Where Hepatitis C is Highly Endemic and Those Where It Is
Not Endemic
Eiji
Tanaka,1,*
Michael
Tacke,2
Masakazu
Kobayashi,1
Yoshiyuki
Nakatsuji,1
Kendo
Kiyosawa,1
Susanne
Schmolke,2
Alfred M.
Engel,2
Georg
Hess,2 and
Harvey
J.
Alter3
Second Department of Internal Medicine,
Shinshu University School of Medicine, Matsumoto 390, Japan1;
Boehringer Mannheim GmbH, 82377 Penzberg, Germany2; and
Department of
Transfusion Medicine, National Institutes of Health, Bethesda, Maryland
208923
Received 14 July 1997/Returned for modification 22 September
1997/Accepted 8 October 1997
 |
ABSTRACT |
We reported previously on an area in Japan where over 30% of the
inhabitants were positive for hepatitis C virus (HCV) antibody. In the
present study, clinical features of hepatitis G virus (HGV) infection
in this area of high endemicity were compared to those in an area where
HCV is not endemic. A total of 400 individuals were selected randomly
from those who were medically screened for liver disease in 1993; 200 were from the high-endemicity area, and the other 200 were from the
no-endemicity area. HGV RNA was measured by reverse transcription and
PCR with primers in the 5' noncoding region. Antibody to HGV envelope
protein E2 was measured by an enzyme-linked immunosorbent assay.
Prevalence of any HGV marker in the high-endemicity area (32%) was
significantly (P < 0.0001) higher than that in the
no-endemicity area (6%); similar differences, 32% versus 3%
(P < 0.0001), had been observed for HCV markers (HCV
RNA and HCV antibody). In areas of both high and no endemicity, HCV
markers were significantly more prevalent in individuals with any HGV
marker than in those without HGV markers, and age-specific prevalence
of HGV markers was distributed similarly to that of any HCV marker.
Among possible routes of HGV transmission that were analyzed, folk
medicine was significant in the high-endemicity area, but blood
transfusion was the major route in the no-endemicity area. The rate of
accompanying viremia in HGV infection (15%) was significantly lower
than that in HCV infection (78%) (P < 0.0001). In
conclusion, HGV infection was highly prevalent in the area of high HCV
endemicity and was closely associated with HCV infection. HGV seemed to
be transmitted via the practice of folk medicine as well as blood
transfusion. HGV resulted in a chronic carrier state less frequently
than did HCV.
| |
INTRODUCTION |
The GB virus C and the hepatitis G
virus (HGV) were identified recently as possible causative agents of
human viral hepatitis (12, 17). Molecular characterization
of these two agents has shown them to be closely related strains of the
same virus, and they are supposed to represent a new genus in the
family Flaviviridae (3). As the nomenclature of
the new virus has not been settled, the term HGV is used in this paper.
HGV, like hepatitis C virus (HCV), is transmissible through blood
transfusion and is associated with acute and chronic infections
(4, 5, 15, 22, 24). Studies on HGV have depended on the
measurement of HGV RNA in serum, which reflects active HGV infection.
Recently, an assay for antibody to HGV envelope protein E2 (HGV-E2
antibody), which indicates recovery from HGV infection, has been
developed (6, 16, 18, 19). The combined use of these assays
has allowed for more comprehensive epidemiological studies of both past
and present HGV infection.
We previously reported on an area in which HCV is highly endemic, where
over 30% of the inhabitants were infected with HCV (10). In
that study, analyses of risk factors for HCV infection elucidated
inapparent modes of parenteral transmission, particularly folk medicine
procedures. In the present study, we determined the prevalence and
patterns of HGV infection in areas of high and low HCV endemicity to
compare the transmission patterns of these two common
Flaviviridae infections.
| |
MATERIALS AND METHODS |
Patients.
A total of 420 individuals over 18 years old (62%
of total inhabitants with corresponding ages) in an area in which HCV
infection was endemic were medically screened for liver diseases in
July 1993. Of those, the first 200 individuals who prepared for
screening were selected randomly for evaluation in this study. Those
subjects included 79 males and 121 females aged 18 to 84 years
(mean ± standard deviation [SD], 56.3 ± 17.7 years).
Medical screening was also conducted in an area in which HCV was not
endemic and which is located near the high-endemicity area. Of 482 individuals (65% of total inhabitants with corresponding ages) who
underwent medical screening in the no-endemicity area, 200 individuals
were selected randomly for evaluation in the same manner as in the high-endemicity area. These control subjects included 48 males and 152 females aged 20 to 89 years (mean ± SD, 56.8 ± 13.4 years).
Data from the HCV high-endemicity area (Arahiro) were reported
previously (10), but the no-endemicity area (Sakaue) was not
involved in the previous study. In both areas the main source of income
is forestry, most people are middle class, Buddhism is the predominant
religion, and the lifestyle does not seem to differ from that in other
parts of Japan. Folk remedies in the areas of high and no endemicity
include acupuncture with needles and so-called "Suidama" therapy,
in which the skin is cut with knives (10). Nonsterilized
knives and needles had been used in the high-endemicity area, but the
use of sterilized instruments began after 1986 under direction of the
public health center. Use of nonsterilized tools had not been noted in
the no-endemicity area. Health screening and blood sample collections
were done in the same manner as reported previously (10).
Informed consent was obtained from each subject. Serum samples were
stored at 
70°C until assayed.
Laboratory tests.
Second-generation HCV antibody, hepatitis
B surface (HBs) antigen, HBs antibody, and hepatitis B core (HBc)
antibody were detected with commercially available enzyme-linked
immunosorbent assay kits (International Reagents Co., Kobe, Japan).
Alanine aminotransferase (ALT) (normal range, 7 to 45 IU/liter) was
measured on a multichannel autoanalyzer.
Measurement of HCV RNA in serum.
RNA extraction and reverse
transcription (RT) were carried out in 100 µl of serum. The serum HCV
RNA was measured by a nested RT-PCR with primers targeting the 5'
noncoding region (14). Procedures to avoid contamination of
samples were implemented throughout the study (11). In each
PCR assay, two negative controls and one positive control of 10 copies/ml were tested in addition to the samples of interest.
Measurement of HGV RNA in serum.
HGV RNA in serum was
detected by nested RT-PCR using primers in the 5' noncoding region as
described previously (21). Briefly, total RNA was extracted
from 100-µl serum samples. After RT with Moloney murine leukemia
virus reverse transcriptase, the first 30 cycles and then the second 30 cycles of PCR were performed (94°C for 1 min, 55°C for 1 min, and
72°C for 1 min). PCR products were analyzed by gel electrophoresis
with 3% agarose. In each PCR assay, two negative controls and one
positive control of 10 copies/ml (15) were tested in
addition to the samples of interest.
In the RT-PCR assays for HCV and HGV RNAs, all negative controls were
negative and all positive controls were positive.
Measurement of HGV-E2 antibody in serum.
HGV-E2 antibody was
measured by an enzyme-linked immunosorbent assay described previously
(18, 19) in which recombinant E2 protein was bound to a
microtiter plate. After addition of diluted serum samples, specifically
bound antibodies against E2 protein were detected with an anti-human
immunoglobulin G conjugated with peroxidase. Positive or negative
results were judged as reported previously (18, 19).
Statistical analysis.
Statistical analyses were performed
with Student's t test, the chi-square test, and Fisher's
exact test. A significance level was set at a P value of
0.05.
| |
RESULTS |
Backgrounds and viral markers in areas of endemicity versus areas
of no endemicity.
Clinical and virological features of the 200 individuals in the high-endemicity area were compared to those of the
200 individuals in the no-endemicity area (Table
1). A history of folk remedies was
significantly more prevalent in the high-endemicity area than in the
no-endemicity area, while histories of surgery and blood transfusion
were similar in the two areas. Prevalence of HGV-related markers was
significantly higher in the area of endemicity than in the
no-endemicity area, as was observed for HCV-related markers. Prevalence
of HBs antigen did not differ between the two areas, but that of any
hepatitis B virus (HBV) marker was significantly higher in the area of
endemicity. Of the 400 subjects, 75 (19%) were positive for HGV RNA
and/or HGV-E2 antibody, 7 (9%) were positive for HGV RNA only, 4 (5%)
were positive for both HGV RNA and HGV-E2 antibody, and 64 (86%) were
positive for HGV-E2 antibody only.
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TABLE 1.
Comparison of clinical and virological characteristics
between individuals in high- and no-endemicity areas
|
|
Age-specific prevalence.
Age-specific prevalences of hepatitis
viruses in the high-endemicity and no-endemicity areas are shown in
Fig. 1. Individuals who had a marker
indicating the existence of viremia were defined as having ongoing
infection, the presence of HBs antigen was defined as indicating HBV
infection, the presence of HCV RNA was defined as indicating HCV
infection, and the presence of HGV RNA was defined as indicating HGV
infection. On the other hand, individuals who had antibody in the
absence of viremia were considered to have resolved or past infection.
Age-specific prevalences of total infection (viremia plus antibody)
were similar for HBV, HCV, and HGV in the high-endemicity area. The
prevalence was around 10% in groups under 50 years old and around 40%
in groups over 50 years old. This difference in distribution between
groups under and over 50 was statistically significant (chi-square
test) for each hepatitis virus: 10% versus 42% for HBV
(P < 0.0001), 8% versus 42% for HCV
(P < 0.0001), and 10% versus 41% for HGV
(P < 0.0001). In the no-endemicity area, the
prevalence did not differ between the two age groups for either HBV,
HCV, or HGV.
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FIG. 1.
Age-specific prevalences of HBV, HCV, and HGV infections
in high-endemicity and no-endemicity areas. Prevalence of exposure is
indicated by both filled and open bars and reflects a positive test for
at least one viral marker (HBs antigen, HBs antibody, and/or HBc
antibody for HBV; HCV RNA and/or HCV antibody for HCV; and HGV RNA
and/or HGV-E2 antibody for HGV). Filled bars indicate a positive test
for a marker of viremia (HBs antigen for HBV, HCV RNA for HCV, and HGV
RNA for HGV).
|
|
Current versus past infection.
To analyze the proportion of
present HGV infections to total HGV infections, cases in the high- and
no-endemicity areas were combined, because the proportions were similar
in each area for each hepatitis virus (6% versus 5% for HBV, 79%
versus 60% for HCV, and 14% versus 17% for HGV, respectively). The
overall percentage of current (to total) infections (15%, 11/75) was
significantly higher for HGV than for HBV (6%, 6/106
[P = 0.04 by the chi-square test]) but significantly
lower than for HCV (78%, 53/68 [P < 0.0001]).
HGV-infected versus noninfected groups.
Clinical and
virological features were compared between groups with and without HGV
infection (including past and present infections) in the high- and
low-endemicity areas (Table 2). A history
of exposure to folk remedies was more frequent in HGV-positive subjects
than in HGV-negative subjects in the high-endemicity area but not in
the no-endemicity area. In contrast, a history of blood transfusion was
significantly more common among HGV-positive subjects than among
HGV-negative subjects in the no-endemicity area. The prevalence of
HBV-related markers did not differ between the two groups, while that
of HCV-related markers was significantly higher in the HGV-positive
group.
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|
TABLE 2.
Comparison of clinical and virological characteristics
between individuals with and without any HGV marker in high- and
no-endemicity areas
|
|
In the high-endemicity area, HGV infection (past and present) was
significantly more common (P = 0.0233 by Fisher's
exact test) in individuals exposed to folk remedies before 1986 (44%, 37/82) than in those exposed after 1986 (11%, 1/9). Similarly, HCV
infection was significantly more common (P = 0.0160 by
Fisher's exact test) in individuals exposed before 1986 (48%, 39/82)
than in those exposed after 1986 (11%, 1/9). Thus, HGV or HCV
infection was less common in individuals who were exposed to folk
remedies after the use of sterilized tools was adopted in 1986.
Mean levels of ALT in serum were compared according to the status of
HCV and HGV RNAs (Table 3). The mean
level was significantly higher in those with HCV and HGV RNAs and those
with HCV RNA alone than in those without HCV or HGV RNA. Other
comparisons among the four groups were not statistically significant,
including the comparison between those with HGV RNA alone and those
without HCV or HGV RNA.
| |
DISCUSSION |
We previously reported that there was a small outbreak of
community-acquired, non-A, non-B acute hepatitis among adults in the
Arahiro area between 1981 and 1982. Subsequent study (10) showed that the outbreak was due to HCV infection spread mainly via
folk remedies in which nonsterilized needles and knives were used.
Age-specific prevalence of HCV antibody showed that inhabitants who
were infected were predominantly over 40 years old when screened in
1986. By 1993 (present study), a high prevalence was found only in
those over 50 years old, suggesting a cohort effect and indicating that
the outbreak of HCV infection had already ceased in the Arahiro area
following the adoption of sterilized tools in the practice of folk
remedies.
HGV-E2 antibody has been reported as a marker of recovery from HGV
infection, based on observations that HGV RNA and HGV-E2 antibody are
generally mutually exclusive and that clearance of HGV RNA generally
coincides with the appearance of HGV-E2 antibody (6, 16,
18). Our results showing that only 5% of individuals with any
HGV marker were positive for both HGV RNA and HGV-E2 antibody further
support the previous observations.
Tacke et al. (18) reported that 2.5% of healthy blood
donors were positive for HGV RNA and that 9% were positive for HGV-E2 antibody. Similarly, Dille et al. (6) reported that 1% of
donors were positive for HGV RNA and that 3% were positive for HGV-E2 antibody. Our data in the no-endemicity area were similar, showing a
1% prevalence of HGV RNA and a 5% prevalence of HGV-E2 antibody. Thus, in an area of low HCV endemicity in Japan, the rates of HGV
infection are similar to those in Western nations.
When we previously compared HCV and HGV infections in the
high-endemicity area by testing HCV and HGV RNAs (23), the
prevalence of HGV infection (5%) appeared much lower than that of HCV
infection (34%). However, with the advent of the HGV-E2 antibody
assay, it became obvious that prevalence of both past and present HGV infection (32%) was as high as that of HCV (32%) or HBV (32%) infection in the high-endemicity area. The prevalence of total infection (past and present infections) for each virus was
significantly higher in the high-endemicity area than in the
no-endemicity area. However, the proportions of the infections that
were active (viremic) were similar in the low- and high-endemicity
areas for each virus. The overall proportions of subjects who were
antigenic or viremic were 6% for HBV, 15% for HGV, and 78% for HCV.
Seventy to 85% of patients with acute HCV infection become chronic HCV
carriers (1, 2, 20) and usually maintain the carrier state
for long periods afterwards (7, 9, 20). Although several
reports have shown that HGV can cause a chronic carrier state (4,
5, 13, 15), the frequency with which it occurs and the rate by which it is maintained has not been clarified sufficiently. Our data
suggest that the rate of persistence does not differ between areas with
different prevalences of HGV infection, and it is higher than that of
HBV but markedly lower than that of HCV.
HGV infection was closely associated with HCV infection both in areas
of endemicity and in areas of no endemicity; individuals with total
(past plus present) HGV infections had high prevalences of HCV markers
and similar patterns of age-specific prevalence. Among possible routes
of HGV transmission, folk remedies were significant in the area of
endemicity, but blood transfusion was most significant in the
no-endemicity area; similar trends were observed in our previous study
of HCV transmission (10). Thus, our results indicate that
HGV is transmissible not only by blood transfusion but also by folk
remedies such as acupuncture and cutting of the skin with nonsterilized
knives and that HGV infection had spread in parallel with HCV in the
area of high HCV endemicity.
ALT levels of individuals with active HCV infection did not differ
among those with and without concurrent HGV infection. Further,
individuals with active HGV infection alone tended to exhibit normal or
very-low-level elevations of ALT. These results are consistent with the
findings of previous studies (4, 5, 8, 13, 21) that
suggested a minimum-pathogenic-effect HGV.
| |
ACKNOWLEDGMENTS |
This research was supported in part by a grant-in-aid from the
Ministry of Health and Welfare in Japan and in part by a grant-in-aid from the Ministry of Education, Science, Sports and Culture (no. 09670529).
We thank members of the South Kiso hepatitis study group for assistance
at the medical screenings performed in the Arahiro and Sakaue areas. We
also thank Kafumi Todoriki for technical assistance.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Second
Department of Internal Medicine, Shinshu University School of Medicine,
3-1-1 Asahi, Matsumoto 390, Japan. Phone: 81-263-37-2634. Fax:
81-263-32-9412. E-mail:
etanaka{at}gipac.shinshu-u.ac.jp.
| |
REFERENCES |
| 1.
|
Aach, R. D.,
C. E. Stevens,
F. B. Hollinger,
J. W. Mosley,
D. A. Peterson,
P. E. Taylor,
R. G. Johnson,
L. H. Barbosa, and G. J. Nemo.
1991.
Hepatitis C virus infection in post-transfusion hepatitis: an analysis with first- and second-generation assays.
N. Engl. J. Med.
325:1325-1329[Abstract].
|
| 2.
|
Alter, H. J.,
R. H. Purcell,
J. W. Shih,
J. C. Melpolder,
M. Houghton,
Q. L. Choo, and G. Kuo.
1989.
Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis.
N. Engl. J. Med.
321:1494-1500[Abstract].
|
| 3.
|
Alter, H. J.
1996.
The cloning and clinical implications of HGV and HGBV-C.
N. Engl. J. Med.
334:1536-1537[Free Full Text].
|
| 4.
|
Alter, H. J.,
Y. Nakatsuji,
J. Melpolder,
J. Wages,
R. Wesley,
J. W. K. Shih, and J. P. Kim.
1997.
The incidence of transfusion-associated hepatitis G virus infection and its relation to liver disease.
N. Engl. J. Med.
336:747-754[Abstract/Free Full Text].
|
| 5.
|
Alter, M. J.,
M. Gallagher,
T. T. Morris,
L. A. Moyer,
E. L. Meeks,
K. Krawczynski,
J. P. Kim, and H. S. Margolis.
1997.
Acute non-A-E hepatitis in the United States and the role of hepatitis G virus infection.
N. Engl. J. Med.
336:741-746[Abstract/Free Full Text].
|
| 6.
|
Dille, B. J.,
T. K. Surowy,
R. A. Gutierrez,
P. F. Coleman,
M. F. Knigge,
R. J. Carrick,
R. D. Aach,
F. B. Hollinger,
C. E. Stevens,
L. H. Barbosa,
G. J. Nemo,
J. W. Mosley,
G. J. Dawson, and I. K. Mushahwar.
1996.
An ELISA for detection of antibodies to the E2 protein of GB virus C.
J. Infect. Dis.
225:293-299.
|
| 7.
|
Farci, P.,
H. J. Alter,
D. Wong,
R. H. Miller,
J. W. Shih,
B. Jett, and R. H. Purcell.
1991.
A long term study of hepatitis C virus replication in non-A, non-B hepatitis.
N. Engl. J. Med.
325:98-104[Abstract].
|
| 8.
|
Kao, J. H.,
P. J. Chen,
M. Y. Lai,
W. Chen,
D. P. Liu,
J. T. Wang,
M. C. Shen, and D. S. Chen.
1997.
GB virus-C/hepatitis G virus infection in an area endemic for viral hepatitis, chronic liver disease, and liver cancer.
Gastroenterology
112:1265-1270[Medline].
|
| 9.
|
Kiyosawa, K.,
T. Sodeyama,
E. Tanaka,
Y. Gibo,
K. Yoshizawa,
Y. Nakano,
S. Furuta,
Y. Akahane,
K. Nishioka,
R. H. Purcell, and H. J. Alter.
1990.
Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus.
Hepatology
12:671-675[Medline].
|
| 10.
|
Kiyosawa, K.,
E. Tanaka,
T. Sodeyama,
K. Yoshizawa,
K. Yabu,
K. Furuta,
H. Imai,
Y. Nakano,
S. Usuda,
K. Uemura,
S. Furuta,
Y. Watanabe,
J. Watanabe,
Y. Fukuda,
T. Takayama, and the South Kiso Hepatitis Study Group.
1994.
Transmission of hepatitis C in an isolated area in Japan: community-acquired infection.
Gastroenterology
106:1596-1602[Medline].
|
| 11.
|
Kwok, S., and R. Higuchi.
1989.
Avoiding false positives with PCR.
Nature
339:237-238[Medline].
|
| 12.
|
Linnen, J., Jr.,
J. Wages,
Z. Y. Zhang-Keck,
K. E. Fry,
K. Z. Krawczynski,
H. Alter,
E. Koonin,
M. Gallagher,
M. Alter,
S. Hadziyannis,
P. Karayiannis,
K. Fung,
Y. Nakatsuji,
J. W. K. Shih,
L. Young, Jr.,
M. Piatak,
C. Hoover,
J. Fernandez,
S. Chen,
J. C. Zou,
T. Morris,
K. C. Hyams,
S. Ismay,
J. D. Lifson,
G. Hess,
S. K. H. Foung,
H. Thomas,
D. Bradley,
H. Margolis, and J. P. Kim.
1996.
Molecular cloning and disease association of hepatitis G virus: a transfusion-transmissible agent.
Science
271:505-508[Abstract].
|
| 13.
|
Masuko, K.,
T. Mitsui,
K. Iwano,
C. Yamazaki,
K. Okuda,
T. Meguro,
N. Murayama,
T. Inoue,
F. Tsuda,
H. Okamoto,
Y. Miyakawa, and M. Mayumi.
1996.
Infection with hepatitis GB virus C in patients on maintenance hemodialysis.
N. Engl. J. Med.
334:1485-1490[Abstract/Free Full Text].
|
| 14.
|
Matsumoto, A.,
E. Tanaka,
T. Suzuki,
H. Ogata, and K. Kiyosawa.
1994.
Viral and host factors that contribute to efficacy of interferon- 2a therapy in patients with chronic hepatitis C.
Dig. Dis. Sci.
39:1273-1280[Medline].
|
| 15.
|
Nakatsuji, Y.,
J. W. K. Shih,
E. Tanaka,
K. Kiyosawa, Jr.,
J. Wages,
J. P. Kim, and H. J. Alter.
1996.
Prevalence and disease association of hepatitis G virus infection in Japan.
J. Viral Hepatitis
3:307-316[Medline].
|
| 16.
|
Pilot-Matias, T. J.,
R. J. Carrick,
P. F. Coleman,
T. P. Leary,
T. K. Surowy,
J. N. Simons,
A. S. Muerhoff,
S. L. Buijk,
M. L. Chalmers,
G. J. Dawson,
S. M. Desai, and I. K. Mushahwar.
1996.
Expression of the GB virus C E2 glycoprotein using the Semliki Forest virus vector system and its utility as a serologic marker.
Virology
225:282-292[Medline].
|
| 17.
|
Simons, J. N.,
T. P. Leary,
G. J. Dawson,
T. J. Pilot-Matias,
A. S. Muerhoff,
G. G. Schlauder,
S. M. Desai, and I. K. Mushahwar.
1995.
Isolation of novel virus-like sequences associated with human hepatitis virus.
Nat. Med.
1:564-569[Medline].
|
| 18.
|
Tacke, M.,
K. Kiyosawa,
K. Stark,
V. Schluter,
B. Ofenloch-Haehnle,
G. Hess, and A. M. Engel.
1997.
Detection of antibodies to a putative hepatitis G virus envelope protein.
Lancet
349:318-320[Medline].
|
| 19.
| Tacke, M., S. Schmolke, V. Schlueter, S. Sauleda,
J. I. Esteban, E. Tanaka, K. Kiyosawa, H. J. Alter, U. Schmitt, G. Hess, B. Ofenloch-Haehnle, and A. M. Engel.
Humoral immune response to the E2 protein of hepatitis G virus is
associated with long-term recovery from infection and reveals a high
frequency of HGV exposure among healthy blood donors. Hepatology, in
press.
|
| 20.
|
Tanaka, E.,
K. Kiyosawa,
Y. Nakatsuji,
Y. Inoue,
T. Miyamura,
J. Chiba, and S. Furuta.
1993.
Clinical significance of antibodies to nonstructural and core proteins of hepatitis C virus in posttransfusion hepatitis patients during long-term follow-up.
J. Med. Virol.
39:318-324[Medline].
|
| 21.
|
Tanaka, E.,
H. J. Alter,
Y. Nakatsuji,
J. W. K. Shih,
J. P. Kim,
A. Matsumoto,
M. Kobayashi, and K. Kiyosawa.
1996.
Effect of hepatitis G virus co-infection on patients with chronic hepatitis C.
Ann. Intern. Med.
125:740-743[Abstract/Free Full Text].
|
| 22.
|
Tanaka, E.,
K. Yamaguchi,
K. Uemura,
M. Kobayashi,
A. Iijima,
K. Kiyosawa,
S. Yagi, and A. Hasegawa.
1997.
Hepatitis G virus/GB virus C infection in patients with chronic non-B, non-C hepatitis.
Int. Hepatol. Commun.
6:137-143.
|
| 23.
|
Tanaka, E.,
Y. Nakatsuji,
M. Kobayashi,
A. Iijima,
T. Ichijo,
H. Imai,
K. Yoshizawa,
T. Sodeyama, and K. Kiyosawa.
1997.
Hepatitis G virus/GB virus C infection in an area of high endemic hepatitis C virus infection.
Hepatol. Res.
7:130-135.
|
| 24.
|
Wang, J. T.,
F. C. Tsai,
C. Z. Lee,
P. J. Chen,
J. C. Sheu,
T. H. Wang, and D. S. Chen.
1996.
A prospective study of transfusion-transmitted GB virus C infection: similar frequency but different clinical presentation compared with hepatitis C.
Blood
88:1881-1886[Abstract/Free Full Text].
|
Journal of Clinical Microbiology, January 1998, p. 110-114, Vol. 36, No. 1
0095-1137/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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Abstract
Introduction
