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1143
Age, Gender, and Local Geographic Variations of Viral
Etiology of Hepatocellular Carcinoma in a
Hyperendemic Area for Hepatitis B Virus Infection
Chuan-Mo Lee, M.D.1
Sheng-Nan Lu, M.D., Ph.D.1
Chi-Sin Changchien, M.D.1
Chau-Ting Yeh, M.D., Ph.D.2
Tsung-Teng Hsu, M.D.1
Jui-Hsiang Tang, M.D.2
Jing-Houng Wang, M.D.1,3
Deng-Yn Lin, M.D.2
Chao-Long Chen, M.D.4
Wei-Jen Chen, M.D.5
1
Liver Unit, Kaohsiung Medical Center, Chang
Gung Memorial Hospital, Kaohsiung, Taiwan.
2
Liver Unit, Linkou Medical Center, Chang Gung
Memorial Hospital, Taipei, Taiwan.
3
Department of Internal Medicine, God’s Help
Hospital, Chiayi, Taiwan.
4
Department of Surgery, Kaohsiung Medical Center, Chang Gung Memorial Hospital, Kaohsiung,
Taiwan.
5
Department of Pathology, Kaohsiung Medical
Center, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Supported by research grants CMRP-442 and
CMRP-513 from Chang Gung Memorial Hospital
(awarded to Chuan-Mo Lee).
Current address for Jing-Houng Wang: Liver Unit,
Kaohsiung Medical Center, Chang Gung Memorial
Hospital, Kaohsiung, Taiwan.
Address for reprints: Chuan-Mo Lee, M.D., Liver
Unit, Chang Gung Memorial Hospital, 123 Ta Pei
Road, Kaohsiung, Taiwan.
Received August 24, 1998; revision received April
9, 1999; accepted April 9, 1999.
© 1999 American Cancer Society
BACKGROUND. There are etiologic variations of hepatocellular carcinoma (HCC) in
different geographic areas. Taiwan is a hyperendemic area for hepatitis B virus
(HBV) infection. Hepatitis C virus (HCV) infection also plays an important role in
HCC development in Taiwan. Identification of local HCV-endemic areas is important to keep HCV from spreading. This study investigated the etiologic variations of
HCC in different geographic areas of Taiwan.
METHODS. The authors evaluated the hepatitis B surface antigen (HBsAg) and
antibodies to HCV (anti-HCV) status of 284 patients (232 male, 52 female) with
HCC. They also evaluated the gender ratio and mean age of these patients.
RESULTS. The mean age of HBsAg positive patients was significantly lower than the
mean age of HBsAg negative patients (52.6 6 12.3 vs. 61.3 6 11.2 years) (P , 0.05).
The male-to-female ratio was 4.5:1 for all HCC patients, 7:1 for HBsAg positive HCC
patients, and 2.8:1 for anti-HCV positive HCC patients. In Chaiyi County in southern Taiwan, the prevalence of anti-HCV in male HCC patients was 52%, significantly greater than that of Taiwan as a whole (27.6%) (P 5 0.07). However, the
prevalence of anti-HCV in male HCC patients in Taipei County in northern Taiwan
was 8.7%, significantly less than that of Taiwan as a whole (P 5 0.043). Of a total
of 65 Chiayi-based HCC patients, 55.4% were anti-HCV positive and 46.2% were
HBsAg positive. In the Chiayi area, results of multiple logistic regression showed
that the HCC patients who were age 60 years or older or who were living in the city
area both had highly HCV-related disease.
CONCLUSIONS. The mean age of patients with HBV-related HCC was significantly
lower than that of patients with non-HBV-related HCC. The male-to-female ratio
for patients with HBV-related HCC was significantly higher than that of patients
with HCV-related HCC. The authors identified an area of Taiwan in which HCVrelated HCC was prevalent. Cancer 1999;86:1143–50.
© 1999 American Cancer Society.
KEYWORDS: hepatitis C virus, hepatitis B virus, hepatocellular carcinoma, geographic variation.
H
epatocellular carcinoma (HCC) is one of the most common malignancies in the world, especially in sub-Saharan Africa and
Southeast Asia.1,2 HCC is estimated to have an incidence of between
250,000 and 1.2 million per year worldwide. Chronic hepatitis B virus
(HBV) infection has been well documented to have a major role in the
development of this cancer.1 Recently, hepatitis C virus (HCV) has
been well established as the most significant etiologic agent for
non-A, non-B hepatitis.3 HCV infection often progresses to chronic
hepatitis or cirrhosis, which may be associated with HCC.4
The prevalence of antibodies to HCV (anti-HCV) in HCC patients
1144
CANCER October 1, 1999 / Volume 86 / Number 7
varies considerably by region, from a low rate of 6.2%
in Mozambique to a high rate of 75% in Spain.5,6 The
highest rates are found in southern Europe and Japan;6,7 intermediate rates in Greece, Saudi Arabia, and
Taiwan;8 –10 and low rates (,20%) in the U.S., Africa,
India, and other countries in the Far East.5,11–13 Localized endemic areas of HCV have also been reported in
Japan,14 Egypt,15 and Cameroon.16 In Taiwan, in contrast to an HBV carrier rate of 15–20% in the general
population,17 the seropositivity rate of blood donors
for anti-HCV is only 1%.18 In Taiwan as a whole, it has
been reported that about 80% of the HCC cases were
related to HBV infection17 and 32% were related to
HCV infection.19 However, Paisha and Tzukuan townships (two townships in southern Taiwan) were reported to be both HBV and HCV-endemic areas, and
HCV was reported to be the main cause of HCC in
Tzukuan township.20 It is important to identify local
HCV-endemic areas to keep HCV from spreading. It
would be important to know the etiologic variations of
HCC in different geographic areas in Taiwan. It would
also be important to know the etiologic variations of
HCC between southern and northern Taiwan. In this
study, we evaluated the hepatitis B surface antigen
(HBsAg) and anti-HCV status and surveyed the gender
and age of patients with HCC from different geographic areas in Taiwan, compared the data on HCC
patients from southern Taiwan with data on those
from northern Taiwan, and tried to find other HCV
endemic areas.
MATERIALS AND METHODS
Two medical centers of the Chang Gung Memorial
Hospital, Kaohsiung Medical Center in southern Taiwan and Linkou Medical Center in northern Taiwan,
were selected as the study hospitals (Fig. 1). There are
approximately 2500 beds for inpatients in Kaohsiung
Medical Center, the biggest hospital in southern Taiwan, at which the patients are from all areas of southern Taiwan. There are approximately 3500 beds for
inpatients in Linkou Medical Center, the biggest hospital in northern Taiwan, at which the patients are
from all areas of northern Taiwan and part of southern
Taiwan. At these two hospitals, patients receiving liver
biopsy or operation for HCC are hospitalized. A total
of 284 (232 males and 52 females) consecutive patients
proven to have HCC cytologically, on biopsy, or surgically with available data from HBsAg and anti-HCV
tests were recruited for this study. Their gender, age at
the time of diagnosis, and place of residence (county
or city) were abstracted from medical records. These
patients were from all areas of Taiwan.
There are 16 counties and 5 cities in Taiwan. In
this study, areas south of Chiayi County (Chiayi
FIGURE 1. H1 represents Kaohsiung Medical Center, Chang Gung Memorial
Hospital; H2 represents Linkou Medical Center, Chang Gung Memorial Hospital;
and H3 represents God’s Help Hospital. The shaded area represents southern
Taiwan. All other areas represent northern Taiwan.
County, Tainan County, Tainan City, Kaohsiung City,
Kaohsiung County, Pingtung County, and Penghu
County) were defined as southern Taiwan (Fig. 1). All
other areas were therefore defined as northern Taiwan
(Fig. 1). A total of 176 patients were from southern
Taiwan and a total of 108 patients were from northern
Taiwan. We compared the HCC patients from the
southern areas with those from the northern areas to
see if there were any trends in age, gender, and viral
etiology (the prevalence of HBsAg and anti-HCV). We
were also interested in finding out whether there were
local geographic variations in the viral etiology of
HCC. If the case number of any county or city was 20
or more for either gender, the viral etiology in these
counties and cities was further analyzed. If a statistical
difference of viral etiology existed, the etiology of HCC
would be studied with data from regional hospitals.
HBsAg and anti-HCV were tested by radioimmunoassay (Abbott Laboratories, North Chicago) and by
a second-generation enzyme immunoassay (Abbott),
respectively. For statistical analyses, the Student t test,
the chi-square test, the Fisher exact test, and a goodness-of-fit test were performed. A three-way analysis
of variance and multiple logistic regression were also
performed as multivariate analyses.
HBV and HCV Distribution in HCC in Taiwan/Lee et al.
1145
TABLE 1
HBsAg and Anti-HCV Status of Hepatocellular Carcinoma Cases by Gender
Male
Female
HBsAg/anti-HCV
Southerna
No. (%)
Northerna
No. (%)
Subtotal
No. (%)
Southernb
No. (%)
Northernb
No. (%)
Subtotal
No. (%)
Total
No. (%)
1/1
1/2
2/1
2/2
15 (9.9)
94 (62.1)
28 (18.3)
15 (9.9)
8 (10.0)
49 (61.3)
13 (16.3)
10 (12.5)
23 (10.0)
143 (61.5)
41 (17.7)
25 (10.8)
1 (4.2)
9 (37.5)
11 (45.8)
3 (12.5)
1 (3.6)
13 (46.4)
10 (35.7)
4 (14.3)
2 (3.8)
22 (42.3)
21 (40.4)
7 (13.5)
25 (8.8)
165 (58)
62 (21.8)
32 (11.3)
1/any
any/1
109 (72.0)
43 (28.2)
57 (71.3)
21 (26.3)
166 (71.5)c
64 (27.7)d
10 (41.7)
12 (50.0)
14 (50.0)
11 (39.3)
24 (46.1)c
23 (44.2)d
190 (66.9)
87 (30.6)
HBsAg: hepatitis B surface antigen; anti-HCV: antibodies to hepatitis C virus.
a,b
There was no significant difference between the southern and northern areas of Taiwan.
c
P , 0.001.
d
P 5 0.019.
RESULTS
Age and Gender of HCC Patients of Different Viral
Etiology
Distribution of viral etiology
Of a total of 284 patients, 66.9% were HBsAg positive
and 30.6% were anti-HCV positive (Table 1). The prevalence of HBsAg positivity among men (71.5%) was
significantly higher than among women (46.1%) (P ,
0.001). In contrast, the prevalence of anti-HCV positivity among women (44.2%) was significantly higher
than among men (27.7%) (P 5 0.019) (Table 1). Of the
190 patients with HBsAg positive HCC, 13.2% were
anti-HCV positive. Of the 94 patients with HBsAg negative HCC, 66.0% were anti-HCV positive (extrapolated from Table 1).
Gender ratio of HCC patients with different viral etiology
The male-to-female ratio of all the recruited HCC patients was 4.5:1 (232:52). The male-to-female ratio was
7:1 (166:24) for HBsAg positive patients, which was
significantly higher than that in anti-HCV positive patients: 2.8:1 (64:23) (P 5 0.019) (Table 1). No significant differences were found in the gender ratio in
either HBsAg positive or anti-HCV positive patients
between the southern and northern areas of Taiwan.
Age-associated factors in HCC patients
The three-way ANOVA analysis showed that age differences existed between the HBsAg positive and HBsAg negative groups. The mean age was 52.6 6 12.3
years for HBsAg positive patients, significantly lower
than the 61.3 6 11.2 years for the HBsAg negative
patients (P 5 0.001). No significant age differences
existed between groups of different gender (P 5
0.9744) and HCV status (P 5 0.3017). Furthermore,
with regard to age, there were no interactions between
HBsAg status and gender (P 5 0.1344) or between
HBsAg status and HCV status (P 5 0.7916). In addition, there were no significant differences in the mean
age between the southern and northern areas of Taiwan.
Geographic Differences of Viral Etiology among Patients
with HCC
Differences in viral etiology between the southern and
northern areas of Taiwan
A total of 152 male and 24 female patients from southern Taiwan were studied. The distribution of HBsAg
and anti-HCV in southern Taiwan was not significantly different from that of northern Taiwan in either
male or female patients (chi-square test and Fisher
exact test, Table 1).
City specific or county specific prevalence of anti-HCV
Because the number of female patients was too small
in any city or county in this study, we did not compare
the prevalence of anti-HCV in these patients. Five
counties or cities had 20 or more male HCC patients:
Taipei County, Chiayi County, Kaohsiung City,
Kaohsiung County, and Pingtung County (Table 2; Fig.
1). The prevalence of anti-HCV (8.7%) among male
HCC patients from Taipei County was significantly
lower than that of Taiwan as a whole (27.6%, P 5
0.043), whereas the prevalence of anti-HCV positivity
(52%) among male HCC patients from Chiayi County
was significantly higher than that of Taiwan as a whole
(P 5 0.007). In contrast, the prevalence of HBsAg
(44.0%) among male HCC patients from Chiayi County
was significantly lower than that of Taiwan as a whole
1146
CANCER October 1, 1999 / Volume 86 / Number 7
TABLE 2
HBsAg and Anti-HCV Status of Male Hepatocellular Carcinoma Patients in the Different Areas Where the Male Patient Numbers
Were Greater than 20
HBsAg/anti-HCV
Taipei
County
No. (%)
Chiayi
County
No. (%)
Kaohsiung
County
No. (%)
Kaohsiung
City
No. (%)
Pingtung
County
No. (%)
Taiwan as
a whole
No. (%)
1/1
1/2
2/1
2/2
1 (4.3)
20 (87.0)
1 (4.3)
1 (4.3)
1 (4.0)
10 (40.0)
12 (48.0)
2 (8.0)
6 (18.8)
20 (62.5)
4 (12.5)
2 (6.3)
3 (10.7)
20 (71.4)
2 (7.1)
3 (10.7)
3 (6.7)
31 (68.9)
5 (11.1)
6 (13.3)
23 (9.9)
143 (61.6)
41 (17.7)
25 (10.8)
1/any
any/1
21 (91.3)b
2 (8.7)d
11 (44.0)a
13 (52.0)c
26 (81.3)NS
10 (31.3)NS
23 (82.1)NS
5 (17.9)NS
34 (75.6)NS
8 (17.8)NS
166 (71.5)
64 (27.6)
HBsAg: hepatitis B surface antigen; anti-HCV: antibodies to hepatitis C virus.
* Compared using goodness-of-fit tests, only the rates for HBsAg postitivity and anti-HCV positivity in Taipei County and Chiayi County are significantly different from the rates for Taiwan as a whole. * aP 5 0.002,
b
P 5 0.036, cP 5 0.007, dP 5 0.043. NS: no significant difference.
TABLE 3
Comparison of HBsAg and Anti-HCV Status by Gender for Hepatocellular Carcinoma Patients in the Chiayi Area and Taiwan as a Whole
Chiayi area
Taiwan as a whole
HBsAg/anti-HCV
Male
No. (%)
Female
No. (%)
Total
No. (%)
Male
No. (%)
Female
No. (%)
Total
No. (%)
1/1
1/2
2/1
2/2
4 (7.7)
21 (40.4)
23 (44.2)
4 (7.7)
1 (7.7)
4 (30.8)
8 (61.5)
0 (0)
5 (7.7)
25 (38.5)
31 (47.7)
4 (6.2)
23 (9.9)
143 (61.6)
41 (17.7)
25 (10.8)
2 (3.8)
22 (42.3)
21 (40.4)
7 (13.5)
25 (8.8)
165 (58.1)
62 (21.8)
32 (11.3)
1/any
any/1
25 (48.1)
27 (51.9)c
5 (38.5)
9 (69.2)c
30 (46.2)a
36 (55.4)b
166 (71.5)
64 (27.6)d
24 (46.1)
23 (44.2)d
190 (66.9)a
87 (30.6)b
HBsAg: hepatitis B surface antigen; anti-HCV: antibodies to hepatitis C virus.
a
P , 0.001, bP , 0.001, cP 5 0.014, dP 5 0.019 (by goodness-of-fit tests).
(71.5%, P 5 0.002) (Table 2). Therefore, HCV infection
is probably the main cause of HCC in Chiayi County.
The prevalence of anti-HCV among HCC patients from a
regional hospital in Chiayi County
The only hospital with HCC treatment facilities and
the biggest hospital (around 700 beds for inpatients)
in Chiayi County was God’s Help Hospital (Fig. 1).
From September 1996 to January 1997, 35 consecutive
patients proven to have HCC cytologically, on biopsy,
or surgically (26 males and 9 females) from Chiayi
County were admitted to this hospital. Half of the
males and two-thirds of the females were anti-HCV
positive. These data further confirmed our findings
that the prevalence of anti-HCV among HCC patients
in Chiayi County was significantly higher than the
prevalence for Taiwan as a whole (P 5 0.009).
Associated factors of anti-HCV positive HCC
A total of 65 HCC patients (52 males and 13 females)
living in Chiayi County were pooled from the 2 medical centers (30 patients from Kaohsiung Medical Center and Linkou Medical Center) and from the regional
hospital (35 patients from God’s Help Hospital). In
total, 55.4% were anti-HCV positive and 46.2% were
HBsAg positive in Chiayi County; these rates were
significantly different from the 30.6% anti-HCV positive and 66.9% HBsAg positive in Taiwan as a whole
(P , 0.001 and P 5 0.002, respectively, by goodnessof-fit test; Table 3). The distributions of anti-HCV
among HCC patients of Chiayi County and in Taiwan
as a whole were significantly different in both genders
(P 5 0.014 and P 5 0.019, respectively; Table 3). In the
Chiayi area, results of multiple logistic regression
showed that HCC patients age 60 or older and living in
the city area were highly HCV-related (Table 4). After
HBV and HCV Distribution in HCC in Taiwan/Lee et al.
TABLE 4
Multiple Logistic Regression Analysis for the Associated Factors of
HCV-Related HCC Patients in the Chiayi Area
Variable
Comparison
Odds ratio
95% CI
Gender
Age (yrs)
Location
Female:male
60 or older:younger than 60
City:rural area
2.05
3.91
12.5
(0.45–9.4)
(1.2–13.1)a
(2.3–70.0)b
HCV: hepatitis C virus; HCC: hepatocellular carcinoma; CI: confidence interval.
a
P , 0.05.
b
P , 0.05.
adjustment for age and geographic location, gender
was found not to be a significant factor. Both age and
location were independently statistically significant.
DISCUSSION
Both HBV and HCV infections are important worldwide problems. In Taiwan, the HBV carrier rate is
about 15–20% of the general population,17 and HCC
ranks second among the causes of death due to malignancy. About 80% of patients with HCC in Taiwan
have previously been reported to be positive for HBsAg.17 In our study, 66.9% of HCC patients were HBsAg
positive. Chronic infection with HCV is also a risk
factor for HCC.4 In Taiwan, 1% of blood donors are
seropositive for anti-HCV.18 Thirty-two percent of
HCC patients have previously been reported to be
anti-HCV positive in Taiwan.19 In our study, 30.6% of
HCC patients were anti-HCV positive.
In this study, the mean age of HCC patients who
were HBsAg positive was 9 years younger than the
mean age of patients who were HBsAg negative. This
result agrees with that of a previous report.21 One of
the reasons for this age difference is that in Taiwan,
most of the HBV-related HCC patients are infected
with HBV by vertical transmission,22 whereas most of
the HCV-related HCC patients are infected with HCV
in adulthood.23 In addition, our study showed that the
age of HCC patients who were both HBsAg positive
and anti-HCV positive was not statistically different
from the age of those who were HBsAg positive and
anti-HCV negative. Our results suggest that HCV infection does not accelerate the occurrence of HCC in
HBV carriers. This result is compatible with a previous
report.18
In our study, male HCC patients had a higher
prevalence of HBsAg positivity than females (71.5% vs.
46.1%, P , 0.001), whereas females had a higher prevalence of anti-HCV positivity than males (44.2% vs.
27.7%, P 5 0.019; Table 1). The male-to-female ratio
was 4.5:1 for all recruited HCC patients (from Table 1).
This ratio was lower than a previous report24 (8:1) but
1147
was compatible with another report.25 The male-tofemale ratio was as high as 7:1 in HBsAg positive HCC
(Table 1). This showed that, in Taiwan, male gender
was an even more significant factor in HBV-related
HCC. The reasons for the gender differences between
HBV-related and HCV-related HCC patients are unclear. Some previous reports suggest that the possible
factors contributing to the male predominance among
HCC patients include the association with HBV, the
higher proportion of male cirrhotics, smoking, and
alcohol drinking.25,26 However, the ratio was 2.8:1 for
anti-HCV positive HCC because of the greater prevalence of anti-HCV positivity among females (Table 1).
Of 190 HBsAg positive HCC patients, 13.2% were antiHCV positive, whereas 66.0% of the 94 HBsAg negative
HCC patients were anti-HCV positive (Table 1). HCV
appeared to play a major role in HBsAg negative HCC.
HCV infection appeared to play a relatively minor role
in HBsAg positive HCC in Taiwan, which agreed with
a previous report.18
There was no significant difference in the prevalence of either HBV or HCV among HCC patients
between the southern and northern areas of Taiwan.
However, the results from the Chang Gung Memorial
Hospital in our study showed local geographic variations of HBV and HCV prevalence in Taiwan, such as
in Chiayi County and Taipei County. In male HCC
patients, the prevalence of anti-HCV in Chiayi County
in southern Taiwan (52%) was significantly greater
than that of Taiwan as a whole (27.6%) (P 5 0.007),
whereas the prevalence in Taipei County in northern
Taiwan (8.7%) was significantly less (P 5 0.041) (Table
2). We further analyzed HCC patients at a different
referral hospital in Chiayi County, God’s Help Hospital, where 54.3% of 35 HCC patients were anti-HCV
positive. These data supported our observation that
the prevalence of anti-HCV among HCC patients in
Chiayi County was significantly higher than the prevalence in Taiwan as a whole. We pooled the 30 patients from Chang Gung Memorial Hospital in Chiayi
County and the 35 from God’s Help Hospital in Chiayi
County, and of the total of 65 patients 55.4% were
anti-HCV positive and 46.2% were HBsAg positive.
This was significantly different from the 30.6% antiHCV positive and 66.9% HBsAg positive in Taiwan as a
whole (P , 0.001 and P 5 0.002 respectively) (Table 3).
These data indicated that in the Chiayi area, both HCV
and HBV infection played important roles in HCC, and
that HCV infection was predominant. In general, it
may take 25–30 years for an HCV infection to cause
HCC.27 There is a possibility, therefore, that HCV infection may have existed in the Chiayi area for a long
time.
Hepatitis C is carried by about 0.5–2.0% of blood
1148
CANCER October 1, 1999 / Volume 86 / Number 7
donors worldwide.3,18,28,29 However, the prevalence is
extremely high in some areas. For example, the rate is
higher than 6% in Zaire,30 6% in regions of Saudi
Arabia,31 and higher than 16% in isolated communities in Japan.32 HCV is most efficiently transmitted by
large or repeated percutaneous exposures, such as
transfusions, transplantation from an infected donor,
or sharing of contaminated needles among injection
drug users.33 The Center for Disease Control estimated
that an average of 150,000 HCV infections occurred
annually in the U.S. during the past decade. Only 6%
of patients report a history of blood transfusion; 46%
report parental drug use.34,35 Persons with percutaneous, sexual, or household exposures account for approximately 60% of the cases of acute hepatitis C, but
persons with no specific source for HCV infection
continue to account for a large number of patients,
and low socioeconomic level is associated with a substantial proportion of these patients.33 Other possible
routes of HCV transmission include hemodialysis,
perinatal exposure, and parental exposures in the
health care setting. Sharing of hygiene items such as
such as combs, razors, toothbrushes, and nail scissors
has been proposed as a possible means of transmission.33,36 Folk remedies, such as acupuncture and cutting the skin using nonsterilized knives, were also
implicated.14
In a study of an HCV endemic area of Japan, the
major route of transmission was iatrogenic contact
with contaminated needles.37 The same transmission
route was implicated in Chiayi County. Genotyping or
nucleotide sequencing of HCV may elucidate the possible causes of HCV infection and possible transmission route38 in this area. It has been reported that
superinfection with HCV increased the HBsAg clearance rates of HBV carriers.39,40 The annual clearance
rate of HBsAg in dual HBV and HCV infected patients
was 2.08%, significantly higher than in HBV infection
alone (0.43%).40 The early clearance of HBsAg in cases
with dual HBV and HCV infection should be considered one factor in the reduction in the number of
HBsAg-related HCC patients in the Chiayi area.
In the Chiayi area, patients with HCC who were
older than 60 years were statistically more likely to
have disease associated with HCV infection. In addition, patients who lived in the city were statistically
more likely to be anti-HCV positive than patients who
lived in the rural areas (Table 4). In the Chiayi area,
modern medical facilities were first introduced into
the city more than 3 decades ago, and then gradually
into the rural areas. The people in the Chiayi area
requested injections when they visited a doctor, and
disposable needles and syringes were not popularly
used until 15 years ago. Therefore, in this area the
people in the city may have had an earlier and greater
chance of receiving iatrogenic contamination of HCV
and developing HCV-related HCC. This is compatible
with a previous study.20 Other possible transmission
routes need to be further investigated.
HCV-related HCC has recently been increasing in
many countries, notably Japan.7,41 However, HBV-associated HCC is being reduced to near-extinction in
Japan, perhaps as a result of the vaccination program
and improved living conditions. In Taiwan, the vaccination program has also reduced the HBV carrier rate
and HCC rate in children.42 In the future, HBV-related
HCC will be markedly reduced in adults, and HCVassociated HCC may increase as in Japan. Interferon
may reduce the chance of, or delay the development
of, both HCV-related and HBV-related HCC.43– 47
Several localized HCV-endemic areas have been
reported in the world.14 –16,20 In Taiwan, Paisha and
Tzukuan townships were reported to be both HBVand HCV-endemic areas; HCV is the main cause of
HCC in Tzukuan township.20 In this hospital-based
study from the two biggest hospitals in Taiwan
(Kaohsiung Medical Center and Linkou Medical Center of Chang Gung Memorial Hospital), we identified
HCV as the main cause of HCC in the Chiayi area and
confirmed this at the biggest local hospital in that
area, God’s Help Hospital. Although the number of
cases studied so far is small, the number is significant.
Further confirmatory studies are being performed. Recently, Wang et al. found that in the Chiayi area, of 73
HCC patients, 53.4% were anti-HCV positive and
46.5% were HBsAg positive.48 The prevalence of antiHCV among HCC patients in different geographic areas is worth studying. Prevention includes considering
all anti-HCV or HCV-RNA positive people to be potentially infectious and preventing all the possible transmission routes mentioned previously in this article.
Screening donor blood for anti-HCV has reduced posttransfusion hepatitis, as has reduction in the use of
shared syringes and needles. After screening donor
blood for anti-HCV, the rate of posttransfusion hepatitis fell 73% in the U.S.49 and Japan50 and fell from
9.6% to 1.9% in Spain.51 There are still several obstacles to the development of an effective vaccine against
HCV. Currently, interferon alone or a combination of
interferon and ribavirin is suggested for treating hepatitis C patients.52–55
In a localized area with a high prevalence of antiHCV positive HCC patients, the prevalence of antiHCV in the population of that entire area must be
investigated. The possible transmission routes should
be identified and blocked. The treatment of hepatitis C
must be aggressive to reduce the chance of spreading
the virus and generating new HCC.
HBV and HCV Distribution in HCC in Taiwan/Lee et al.
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