Our research found 13 patients with genotype D, which was quite rare in Taiwan.
The male/female ratio was 0.86:1, and the average age was 49.3 year-old (male/female:
54.5/44.9 year-old) without big differences from the average age in patients with
genotype B or C.
The lab results were as following: average AST was 67 U/L, average ALT was 43
U/L, average AFP was 11 ng/ml, the rate for abnormal AFP was 16.7%,
HBeAg-positive rate was 15.4%, the average HBV DNA was 10,309,203 IU/ml and the
rate for HBV DNA greater than 2,000 IU/ml was 100%.
The places of birth and residence were almost all in Pingtung County. Only one of
them lives in Chiayi County. Twelve of the total 13 patients were aborigines: 10 of
them were Paiwan tribe and other 3 were Rukai tribe, Tsou tribe and non-aborigine. All
of them indicated that they did not shared needles with others; 2 (15.4%) of them had
received blood transfusion; 6 of them (46.1%) had surgeries before; and 5 (38.5%) of
them had tattoo or piercings (Table 7).
DISCUSSIONS
This research found that among patients with HBV infection in Taiwan, the
aborigines had fewer risk factors for HCC than the non-aborigines, such as lower
HBeAg-positive rate (5.3% vs. 10.2%, p-value<0.0001), lower average HBV DNA viral
load, lower rate to have HBV DNA greater than 2,000 IU/ml (27.4% vs. 36.7%,
p-value<0.0001) and higher prevalence for genotype B (92.7% vs. 72.7%,
p-value<0.05). Those patients with HBV infection who lived on outlying islands (34.2%
in Penghu County and 41.7% in Lienchiang County) mainly had genotype C (60%) and
patients who lived on the main island mostly had genotype B (89%). The prevalence of
genotype B in the aborigines group was significantly higher than in the non-aborigines
group (92.7%), especially the Tsou and the Paiwan, which was about 97%. Furthermore,
our research found 13 patients with genotype D, a very rare genotype in Taiwan.
Patients with genotype D were clustered in the local Paiwan tribe of Pingtung County.
These subjects had higher HBV DNA (greater than 2,000 IU/ml) without the experience
of sharing needles with others and some of them had received blood transfusion or
surgeries or tattoo or piercings.
Domestic research found that risk factors among patients with HBV infection for
HCC included male, elderly age, abnormal ALT value, HBeAg- positive result, liver
cirrhosis, higher HBV DNA viral load, genotype C, no mutation on precore 1896 and
mutation on BCP (1762/1764) [26]. This research showed that among asymptomatic
HBV carriers who lived in the rural areas in Taiwan, the HBeAg-positive rate was 8%,
with higher rate in the non-aborigine group than in the aborigine group (10.2% vs. 5.3%,
p-value<0.0001). This is much lower than the findings from other studies on
asymptomatic HBV carriers (20%) [60]. There were no significant differences between
the ALT values of the non-aborigines and that of the aborigines. However, the average
AST value and the rate of having a drinking habit were both higher in the aborigine
group, and therefore it was presumed that the high AST might be resulted from drinking
habit.
In addition, 29% of the HBV carriers had no detectable HBV DNA viral load in
their blood, and 32.7% of them had HBV DNA greater than 2,000 IU/ml. Both the
average viral load and the rate of HBV DNA greater than 2,000 IU/ml were higher in
the non-aborigine group than in the aborigine group (36.7% vs. 27.4%, p-value<0.0001).
Regardless of HBeAg being negative or positive, the aborigines had much higher
possibilities of being genotype B than the non-aborigines in any age group (HBeAg-
positive group: 83.3% vs. 44.5%, p-value<0.0001; HBeAg- negative group: 93.7% vs.
are part of the world Austronesian population and have lower risk of HCC than
non-aborigines, may have different specific immune system or genetic factors from
non-aborigines. This may result in stronger immunity against HBV.
Researches have shown that patients with HBV infection have higher risks for liver
cirrhosis and HCC and HBV infection, which is the main reason for HCC [1, 61].
According to statistics from the Department of Health, the standardized mortality rate of
chronic liver diseases and liver cirrhosis--which is the mainly cause of death in
aborigines with age of 25-44 year-old--have been higher in the rural areas or in the
aborigines who also have shorter life span (68.5 years vs. 77.9 years) than in the whole
country. Yet the standardized mortality rate of HCC is lower in aborigines [7, 14]. In
addition, our research found that the aborigines with HBV infection had fewer risk
factors for HCC, higher average AST and higher rate of drinking habit (40%) than the
non-aborigines. Hence, the main causes for the aborigines dying from chronic liver
diseases are alcoholic hepatitis or other hepatitis, but not hepatitis B infection.
Furthermore, the aborigines live in rural areas, where transportation is inconvenient,
medical resource scarce, and health-care system inadequate. These may all be
contributing factors for death from chronic liver diseases.
Therefore, it is predicted that if we can provide easier medical access in rural areas,
promote the 2A3C of community health care system (accessibility, accountability,
comprehensiveness, coordination and continuity) and encourage people to quit drinking,
it may greatly decrease the severity of liver diseases of the aborigines and in rural areas.
The analysis of genotypes found out that in subjects with all kinds of genotype, the
prevalence of genotype B was 75.6%. If we simply calculated genotype B or C, the
prevalence of genotype B was 80.6%, which was similar to the 80% from the domestic
researches. However, if we deducted people from outlying islands (Lienchiang County
and Penghu County), the prevalence of genotype B was raised to 89.1%, which was
much higher than 80% [35]. The main genotype in the outlying islands (58.3% in
Lienchiang County and 65.8% in Penghu County) was C (59.7%), and the main
genotype in the main island was B (East [92.7%] > Central [91.22%] > North [90.2%] >
South [82.0%]). This result was consistent with the results from other domestic
researches, which was that people who immigrated from the mainland China to Taiwan
after World War II had higher possibility to have genotype C [19].
The rate of genotype B was higher in the aborigine group (92.7%) than in the
non-aborigine group (72.7%) with p-value<0.05 in any age group. It has also been
indicated that the prevalence of genotype B had been increasing from age 40 onward in
with aging, patients with more severe liver diseases (e.g. genotype C) had died early
with being selected naturally, no matter if they are aborigines or not. Therefore, the
higher prevalence of HBV genotype B is found in the elders.
If we further stratified the patients into HBeAg-positive and HBeAg-negative
groups, the prevalence of genotype B was still higher in the aborigine group (83.3% and
93.7%). Among the aborigines, the prevalence of genotype B was the highest in the
Tsou (97.8%), then in the Paiwan (96.4%), and then in the Atayal (88.1%), with no
statistically significant differences. The reason for the prevalence of genotype B in the
aborigines to be as high as 92.7% was presumed to be because when the Austronesian
peoples immigrated, the aborigines in Taiwan had a closer relationship with the
Austronesian people who lived in the southeast of mainland China than the other areas.
The reasons for the prevalent rate of genotype B to be the highest in the Tsou people
(Tsou and Rukai tribe) were presumed to be because they lived in very remote areas
after immigrated to Taiwan, the rate of both parents being in the same tribe was as high
as 95.6%, and that they mostly married within the same tribe.
After we recruited patients from 42 townships in Taiwan, we found 13 patients
with genotype D, which was rather rare in Taiwan. Genotype D is common in Europe,
South Asia (India), and the Solomon islands, but very rare in Taiwan. The average age
of these 13 patients was 49.3 years old (the male patients were about 10 years older than
the female patients). The lab results showed that the average AST and ALT were
unusually high, the rate for HBeAg-positive was high (15.4%), the average HBV DNA
was between genotype B and C, and all of them had HBV DNA greater than 2,000
IU/ml. Some very interesting findings include that they were almost clustered in the
local Paiwan tribe of Pingtung County. The questionnaire showed that all of them did
not share needles with others in the past and some of them had received blood
transfusion or surgeries or tattoo or piercings. In addition, combining with patients with
genotype B or C co-infection, among all these patients with HBV infection in rural
areas of Taiwan, about 1.8% of them had genotype D. Would this rare genotype be
related to the history of family relationship or body fluid or blood transmission? Where
did this rare HBV genotype D come from? How would it be transmitted into Taiwan?
These are all issues that are worth investigating in a cluster of patients with HBV
genotype D found in the local area of southern Taiwan.