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Prevalence and determinants of biochemical dysfunction of the liver in Atayal Aboriginal community of Taiwan: Is betel nut chewing a risk factor?

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Open Access

Research article

Prevalence and determinants of biochemical dysfunction of the liver

in Atayal Aboriginal community of Taiwan: Is betel nut chewing a

risk factor?

Ching-Feng Lin

1,2,5

, Tun-Jen Shiau

1

, Ying-Chin Ko

3,4

, Ping-Ho Chen

4

and

Jung-Der Wang*

1

Address: 1Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University, College of Public Health and Department of

Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, 2Department of Health, Executive Yuan, Taiwan, 3Department of Public

Health, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, 4Division of Environmental Health and

Occupational Medicine, National Health Research Institutes, Taiwan and 5School of Public Health, Taipei Medical University, Taiwan

Email: Ching-Feng Lin - baliowl@mail.bali.doh.gov.tw; Tun-Jen Shiau - adlcf@doh.gov.tw; Ying-Chin Ko - ycko@nhri.org.tw; Ping-Ho Chen - phchen@nhri.org.tw; Jung-Der Wang* - jdwang@ntu.edu.tw

* Corresponding author

Abstract

Background: We address the independent and interactive roles of habitual betel quid chewing

and other known risk factors for biochemical dysfunction and cirrhosis of the liver.

Methods: To determine the prevalence rates and risk factors associated with biochemical

dysfunction of the liver, a total of 3,010 adult residents in an Atayal Aboriginal community were invited to participate in the study. Abdominal ultrasonography was used to diagnose liver cirrhosis.

Results: There were 2,063 Atayal Aboriginal and 947 non-Aboriginal in this study. The result

showed overall prevalence rates for hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) were 21.2 % and 2.9 %, respectively. There were 16.5 %, 15.1 % and 22.4 % subjects with abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transpeptidase (GGT), accordingly. Multiple logistic regression analysis showed that combined infections with HBV and HCV presented with the highest risks with OR (odds ratio) and 95% CI (confidence interval) of 4.2 (1.2–17.4) and 3.8 (1.0–14.1), respectively for elevation of ALT and AST; followed by alcohol (1.7 and 3.1), male gender (1.7 and 1.6), betel quid (1.5 and 1.3), smoking (1.4 and 1.8), and aboriginal (1.4 and 1.3). There is effect-measure modification between viral infection and betel quid chewing for increased severity of abnormal ALT elevation. Among 1,382 subjects consenting to abdominal ultrasonography, 41(3.0%) were found to have liver cirrhosis with the same factors associated with higher risks.

Conclusion: In addition to infections with viral hepatitis B and/or C, we found Atayal Aboriginal,

males, current smokers, drinkers and betel quid chewers were independently associated with biochemical dysfunction and probably cirrhosis of the liver. Further study is needed to corroborate the above hypothesis.

Published: 27 April 2008

BMC Gastroenterology 2008, 8:13 doi:10.1186/1471-230X-8-13

Received: 19 March 2007 Accepted: 27 April 2008 This article is available from: http://www.biomedcentral.com/1471-230X/8/13

© 2008 Lin et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Background

Health inequity and disparities have been demonstrated to exist between Aboriginal and non-Aboriginal in the USA, Australia, Taiwan and other countries [1]. In Aus-tralia, for almost all disease categories, rates for Aboriginal were higher than those for other Australians, which were mainly attributed to the hypothesis of social and eco-nomic inequality [2-4]. Such an inequality may result in an increase of not only infectious diseases but also almost every kind of diseases associated with diet, exercise pat-terns, apathy and health behavior, such as alcohol drink-ing, cigarette smokdrink-ing, betel quid chewing and obesity [1].

The population of Taiwan is 23 million, consisting of Hokkien (73%), Hakka (12%), Mainland Chinese (13%), and Aboriginal (2%) ethnic groups [5]. There are twelve Aboriginal tribes in Taiwan and constitute approximately 460,000 Aboriginal of the Taiwanese (general) popula-tion. Although there have been long term mixed marriage with other ethnic groups, Taiwan Aboriginal still pre-served their own languages, customs and social organiza-tions. In hereditary characteristics, they are markedly different from the rest of Taiwanese population [6]. Their health status, as evaluated by life expectancy, mortality rates and the prevalence and incidence of various diseases such as accident, liver disease and other diseases, was worse than that of the general population in Taiwan [1]. A more recent investigation indicated that the discrepancy of life expectancy between Aboriginal and non-Aboriginal were slightly reduced, but the life expectancy of Aborigi-nal were on average 10 years less than that of the general population, with a standardized mortality ratio approach-ing 2-fold [7].

Taiwan is known for the high prevalence of chronic hepa-titis B virus (HBV) infection, with a positive rate of 15–20 % for hepatitis B surface antigen (HBsAg) [8,9], which was also reported among Aboriginal people [8]. The preva-lence of hepatitis C infection was around 2–4 % [10]. Aboriginal in Taiwan were also found to have a high prev-alence rate of alcoholism, estimated at about 20–30 % [11,12], which may result in abnormal liver function or even chronic liver injury. Thus, abnormal liver function in Aboriginal people in Taiwan has usually been considered to be virus or alcohol related.

Betel quid chewing is a prevalent habit in 10–20% of the general population [13], and is also part of traditional Aboriginal culture usually taken with alcohol during festi-val or traditional ceremony in Taiwan [14]. The betel quid prepared in Atayal aboriginal community of Taiwan is quite different from those in other parts of the world. It usually consists of 2 halves of a fresh areca nut (fruit of the

Areca catechu Linn.), sandwiched with a piece of the betel

leaf, and white slaked lime paste, instead of the reddish inflorescence. Betel quid chewers generally swallow the saliva completely, thus bathing the epithelial lining of the upper digestive tract with the toxins released during chew-ing. Such a practice may increase the possibility of toxic effects of betel quid at target organs other than the oral cavity [15]. In 2004, the International Agency for Research on Cancer (IARC) declared chewing of betel quid, by itself, to be a Group 1 carcinogen and the areca nut to be, correspondingly, a Group 1 carcinogen [16]. Chewing betel quid independently contributes to the risk of oropharyngeal cancer [17-19], oral mucosal lesions [20], oral leukoplakia [21], oral submucous fibrosis (OSF) [21], liver cirrhosis [22,23], hepatocellular carcinoma (HCC) [24], diabetes mellitus [25] and adverse outcomes with use during pregnancy [26]. Endogenous formation of areca-nut-derived nitrosamines was found in vivo or in

vitro studies, suggesting that the damage of liver could

partly result from metabolite of the areca nut [27]. Chronic inflammation of the liver appears to be a risk fac-tor for cirrhosis regardless of the underlying etiology [28-30]. Experimental study has indicated persistent hepato-cellular damage after chronic feeding with betel quid [31,32]. However, the role of betel quid chewing in the development of liver injury and/or cirrhosis, and its inter-action with other known risk factors, have not drawn much attention, although Lin et al and Tsai et al inde-pendently published case-control studies with cirrhosis and/or chronic liver diseases suspected to be associated with this habit [22,23]. In this study we address the inde-pendent and interactive roles of habitual betel quid chew-ing and other known risk factors for biochemical dysfunction and cirrhosis of the liver.

Methods

Design

There are 12 linguistically distinct Aboriginal tribes in Tai-wan, which constitutes about 2 % of the total Taiwanese population. They mainly reside in the eastern plains and central mountainous area where is mainly above a height of 500 m. The ethnic status was classified into two groups, "Aboriginal" and "non-Aboriginal". Aboriginal were defined when at least one of the two parents was Atayal Aboriginal. Also, non-Aboriginal were defined when both parents were not Atayal Aboriginal. The non-Aboriginal in this study were mainly Hokkien and Hakka people living in the same community. In this study, we selected the Fushin district in Taoyuan county, which was in the catch-ment area of our investigations and locates in the north-ern part of Taiwan with a total of 4,665 residents who were above 20 years of age. Every citizen in the district was invited to participate in a comprehensive physical exami-nation including a detailed questionnaire of health his-tory. A total of 3,010 subjects (64.5%) responded, which

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included 2,063 Atayal Aboriginal and 947 non-Aborigi-nal.

This study was first approved by the medical research eth-ics committee of the hospitals of the Department of Health of Taiwan before commencement, of which the certification number is 900808-03. The informed consent was provided both orally and in writing, which was con-ducted under the assistance of local public health nurses who can speak Atayal language.

Data collection and analysis

After obtaining an informed consent from every subject, 10 c.c. of blood was drawn from every respondent's ante-cubital vein. All blood samples were centrifuged and serum was frozen down to – 30°~-70°C until they were tested for hepatitis B & C markers and biochemical func-tion of the liver, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltranspeptidase (GGT).

Test for HBsAg and anti hepatitis C virus (HCV) was con-ducted by radioimmunoassy with reagents supplied by Abbott company (U.S.A.), and read by clinical Gamma Counter (L.K.B of U.S.A.) with both positive and negative controls. If the reading was on the borderline, the test was repeated 2~3 times. If it consistently showed positive, then the result was considered positive. Liver function tests were performed with reagents supplied by Hitachi 7400. All these serological tests were conducted in the central laboratory of the Taoyuan general Hospital, Department of Health. Every subject was also asked to fill out a questionnaire containing basic demographic infor-mation and previous medical history, ethnic group, alco-hol drinking, smoking, betel quid chewing, blood transfusion and intravenous injection. Every case was physically examined by a doctor. The history of blood transfusion and intravenous injection was verified from the medical records of the local public health stations, which were the only resource providing health services to the people residing in mountainous area and the data were with a confirmed rate of 99%. Every subject was also invited to receive abdominal ultrasonography examina-tion (Toshiba SAL-38B, Tokyo, Japan).

Dependent variables

Separate analyses were conducted for biochemical liver function (ALT, AST, GGT) and liver cirrhosis. The dichot-omous variables, biochemical liver function, were coded as ALT (>=37; < 37)/AST (>=37; < 37)/GGT (>=61/<61). Data was separately analyzed for risk factors associated with biochemical liver function/liver cirrhosis. The only one hepatologist conducted all the real time ultrasonogra-phy and scored on 10 parameters [33], which ranged from 0, 0.5, 1(mild), 2(moderate), and 3(marked) for each

parameter. The more specific parameters for cirrhosis included nodular liver surface, coarse echotexture, irregu-lar narrowing of hepatic veins and a summed score of more than 4.0 indicated cirrhosis of liver with an accuracy of 95.6% [33].

Independent variables

Potential risk factors included ethnic group, gender, age, body mass index (BMI), cigarette smoking, alcohol con-sumption, betel quid use, HBsAg(+), and anti-HCV(+). Body mass index (BMI) was calculated (BMI = weight/

height2, kg/m2). The smoking and drinking behaviors

were coded as current smokers/drinkers (continual smok-ing/drinking least once a week, irrespective of quantity), never smokers/drinkers/(those who never smoked/ drank), or former smokers/drinkers (those who quit smoking/drinking at least one year prior the survey). Betel quid chewing behavior, was coded as betel quid chewers (chewed at least once a week, irrespective of quantity) or never chewers (those who never chewed).

Statistical analyses

All the information of medical history and laboratory results was collected and put into computer file and proc-essed and analyzed by SAS version no. 6.02. A chi-square test was performed for each univariate analysis first to screen in potentially significant variables. Then, we calcu-lated odds ratio (OR) with 95% CI of abnormal biochem-ical function of the liver through multivariate modeling after controlling major risk factors, including age, gender, BMI, ethnic group, alcohol drinking, cigarette smoking, betel quid chewing and hepatitis B & C status. A backward stepwise procedure was undertaken with a selection of p-value less than 0.001 to be kept in the final model.

Results

Originally we invited 4,665 residents who were above 20 years of age to take part in the study. Some residents did not participate in the study, because they have already taken jobs in urban area and moved out of the village. In total, we successfully collected blood samples and per-sonal information from 3,010 subjects in this Atayal Abo-riginal community of Taiwan. Because our local public health nurses went on door-to-door visits to every house-hold in the community, almost all people who still resided in the community were screened. 48 % of them were males. Table 1 depicted the distribution of risk fac-tors associated with abnormal liver function by using a chi square test in the univariate analysis. The average age was 49.8 ± 10.2 years old, with about more than one third of them in the age range of 41~60 years old (36.9%), as sum-marized on Table 1. Among these participants, there were 2,063 (68.5%) Aboriginal, in which about one fifth showed an abnormal ALT, 18.2% showed an abnormal AST and 28.6% an abnormal GGT. Aboriginal

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consist-ently showed higher proportions of smoking, alcohol drinking, betel quid chewing, overweight, and abnormal transminases than did non-Aboriginal. In addition, ciga-rette smokers, alcohol drinkers, HBsAg carriers, people with habitual betel quid chewing, and people who were infected by HCV were found to have significantly higher proportions of abnormal liver transaminases (all p value < .001). The overall prevalence rates of HBsAg and anti-HCV were 21.2 % and 2.9%, respectively.

Table 2 summarizes the results of multiple logistic regres-sion modeling by using a backward stepwise procedure to choose the major risk factors (p value < 0.001) of abnor-mal biochemical liver function. After adjustment for gen-der, BMI, viral hepatitis B and C infections, smoking, alcohol drinking and betel quid chewing, we found that Aboriginal were more likely to develop abnormal eleva-tion of liver transaminases than non-Aboriginal, with an OR of ALT 1.4 (95 % C.I., 1.2–1.7), AST 1.3 (95 % C.I., 1.1–2.2), and GGT 1.5 (95 % C.I., 1.2–2.9). We also found that betel quid chewing was independently associ-ated with abnormal elevation of liver transaminases, with an OR of ALT 1.5 (95 % C.I., 1.1–1.8) and AST 1.3 (95 % C.I., 1.1–1.7). Current alcohol drinking increased likeli-hood of developing abnormal elevation of liver transam-inases after controlling other risk factors, with 4.7 times of risk for GGT. Similarly, current smoking, male gender, and viral hepatitis B or C infection also showed a signifi-cantly increased likelihood of abnormal elevation of ALT, AST, GGT after controlling other risk factors as summa-rized on Table 2. Increased BMI (> 25) was also associated

with increased risks for abnormality in ALT and GGT. There are linear trends for increased severity levels of ALT elevation for both hepatitis virus infection and betel quid chewing, and there was about 4.7 % (140/3010) of the study population with more than 5 times of elevation of ALT. After stratification by different levels of elevated ALT, the multiple logistic regression analysis also showed a synergistic effect between viral infection and betel quid chewing, as summarized in Table 3.

Only 1382 subjects came for abdominal ultrasound examination, which detected 41 cases (3.0 %) with cirrho-sis of liver. Among them, 4 cases of liver cancer were sub-sequently diagnosed and verified with pathology. All 4 cases were male Aboriginal with positive HBsAg and a habit of alcohol drinking, except one quitted about 10 years ago. The average age of subjects with cirrhosis of liver was 46 ± 14 years. Approximately 96 % of liver cir-rhosis subjects had a history of alcohol drinking (12.5 % of them have already quitted) and 45 % of them showed positive HBsAg. After controlling for other risk factors, we found that Aboriginal were associated with liver cirrhosis, with an adjusted OR of 1.8 (95 % C.I., 1.4–3.2), as shown in Table 4. Similarly, former and current alcohol drinking increased risks of developing cirrhosis of liver with 1.6 and 2.1 times, respectively. Betel quid chewing was inde-pendently associated with cirrhosis of liver, with an adjusted OR of 1.7 (95 % C.I., 1.2–2.3).

Table 1: Frequency of demographic factors and risk factors stratified by ethnicity, and abnormal elevations of biochemical functions (ALT, AST, and GGT) in an Atayal aboriginal community of Taiwan

Ethnic groups

Aboriginal Nonaboriginal ALT>=37(%) AST>=37(%) GGT>=61(%) No. of subjects 2063 947 496(16.5) * 454(15.1) * 675(22.4) * Aboriginal 429(20.8) * 377(18.2) * 591(28.6) * Age(year) ≤ 20 3 1 1(25.0) 0(0) 1(25.0) 21–40 732* 262 191*(19.2) 194*(19.5) 240(24.1) 41–60 743 370 211(18.9) 190(17.0) 317*(28.5) ≥ 61 585 314 93(10.3) 70(7.8) 116(12.9) Gender Male 992 460 357(24.5) * 321(22.1) * 508(34.9) * Female 1071 487 139(8.9) 133(8.5) 167(10.7) Cigarette smoking 930* 252 248(21.0) * 339(28.7) * 460(38.9) * Alcohol drinking 1226* 267 295(19.8) * 410(27.5) * 577(38.6) * Betel quid chewing 995* 122 399(35.7)* 375(33.6)* 290(26.0) HBsAg(+) 441 197 153(24.0) * 147(23.1) * 154(24.1) * Anti-HCV(+) 61 25 31(36.1) * 33(38.3) * 31(36.1) * BMI>25 840* 277 384(34.4) * 341(30.5) 392(35.1)* *p < 0.001 for crude chi-square test of association between individual risk factors and aboriginal ethnicity

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Table 2: Frequency, odds ratio(OR) and 95%CI (confidence interval) for different risk factors of abnormal biochemical liver function estimated from multiple regression logistic model after adjustment for age, gender, and education level

Variables ALT AST GGT

No. of Cases No. of Cases No. of Cases

>=37/<37 OR (95% CI) >=37/<37 OR(95% CI) >=61/<61 OR(95% CI) Ethnic group Non-Aboriginal 68/868 1.0 66/870 1.0 84/852 1.0 Aboriginal 340/1724 1.4(1.2–1.7) 429/1635 1.3(1.1–2.2) 590/1472 1.5(1.2–2.9) Alcohol drinking Never 113/1402 1.0 85/1430 1.0 97/1417 1.0 Former 16/127 1.1(0.6–2.0) 14/129 1.0(0.5–1.9) 16/129 1.0(0.5–1.9) Current 279/1068 1.7(1.2–2.2) 396/951 3.1(2.4–4.3) 561/951 4.7(3.3–6.0) Cigarette smoking Never 160/1666 1.0 156/1670 1.0 214/1612 1.0 Former 19/76 1.4(0.8–2.2) 22/73 1.7(1.2–3.1) 27/68 1.1(0.6–16) Current 229/1068 1.4(1.1–1.8) 317/766 1.8(1.3–2.2) 433/649 1.6(1.2–2.1) Betel quid chewing

No 117/1584 1.0 129/1613 1.0 154/1857 1.0 Yes 282/1117 1.5(1.1–1.8) 246/983 1.3(1.1–1.7) 136/527 0.7(0.5–1.1) Gender Female 117/1439 1.0 139/1417 1.0 167/1387 1.0 Male 291/1158 1.7(1.5–2.3) 356/1093 1.6(1.2–2.0) 507/942 2.0(1.9–2.9) BMI <=25 214/1659 1.0 326/1547 1.0 374/1499 1.0 >25 193/929 1.9(1.5–2.4) 167/955 1.0(0.7–1.1) 295/825 1.9(1.5–2.3) HBV/HCV -/- 232/971 1.0 299/1904 1.0 470/1731 1.0 +/- 132/496 1.8(1.4–2.3) 148/480 1.7(1.3–2.2) 148/480 0.8(0.6–1.0) -/+ 27/49 3.7(3.2–9.2) 26/50 3.1(2.1–6.2) 25/51 2.0(1.3–4.4) +/+ 5/5 4.2(1.2–17.4) 5/5 3.8(1.0–14.1) 6/4 2.3(0.7–11.0) ALT:Alanine aminotrnsferase; AST:Alanine aminotrnsferase; GGT:γ-glutamyl transpeptidase; +:positive; -:negative; OR: odds ratio

Table 3: Frequencies and OR (odds ratio) and 95%CI (confidence interval) for betel quid chewing and infection with HBV/or HCV stratified by different severity levels of abnormal alanine transaminase (ALT) estimated from multiple logistic regression model after adjustments for alcohol and cigarette consumptions, age, ethnicity, BMI (body mass index) and gender

Levels of ALT elevation ≤ 37 [1 ×] OR (95%CI) >37–≤111 [1–3 ×] OR (95%CI) >111–≤185 [3–5 ×] OR (95%CI) >185 [>5 ×] OR (95%CI) Betel Quid Chewing HBV/or HCV No. of subjects No. of subjects No. of subjects No. of subjects No - 1005 1.0 135 0.9 (0.6–1.2) 40 0.5 (0.3–0.8) 23 0.3 (0.1–0.8) + 318 1.3 (1.2–1.5) 18 1.6 (1.2–1.9) 21 1.8 (1.3–2.3) 24 2.3 (2.1–2.7) Yes - 935 1.1 (0.8–1.5) 31 1.3 (1.1–1.3) 23 1.5 (1.2–1.9) 28 1.7 (1.4–2.1) + 256 1.5 (1.2–1.8) 36 2.3 (1.9–2.6) 52 3.1 (2.5–3.6) 65 4.2 (3.5–4.7) HBV: HBsAg(+)

HCV: hepatitis C virus infection +: positive

-: negative

OR(95%): odds ratio(95%CI) 1 ×: upper normal limit

1–3 ×: one to three times of upper normal limit 5 ×: five times of upper normal limit

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Discussion

Although the frequencies of abnormal ALT, AST, and GGT among Aboriginal were found to be all above 18% and significantly higher than in non-Aboriginal (all p's < 0.001), such associations might not be necessarily causal, especially using a cross-sectional design, requires careful evaluation. In this study, most people in this Aboriginal community were employed by industry related to tourism and sightseeing. It also attracted a lot of non-Aboriginal people to work and reside in the community and pro-vided us an excellent opportunity to compare the findings in these ethnic groups. In fact, the proportions of betel quid chewers among Aboriginals (48.2%) and non-Abo-riginals (12.8%) estimated from this study were similar to those reported before [12,16], indicating a relatively rep-resentative sample from both ethnic groups. Since the coverage proportions of National Health Insurance for non-Aboriginal and Aboriginal people of this community were about 97% and 93 %, respectively, and both of them were waived from partial co-payment, the likelihood of selection bias seems very low.

After controlling all known risk factors for liver diseases (including viral infections, smoking, alcohol drinking, overweight, gender and ethnicity), there was still 1.3 – 1.5

times of increased odds ratio in Aboriginal. Thus, the asso-ciation deserves our further consideration. There were fol-lowing possible random errors on measurements of determinants: The history of ethnic group was generally very accurate because only Aboriginals were entitled to a complete waiver for partial co-payment if treated by a doc-tor. The BMI of every subject was calculated by a nurse immediately after physical measurements of body weight and height. Thus, only the history of alcohol drinking, smoking and betel quid chewing might have a chance to be randomly misclassified, which usually lead toward the null or underestimation.

Except for the unknown factors that might cause non-ran-dom errors, our multivariate models controlled for all the known major risk factors, including viral hepatitis B and C, current alcohol drinking and/or cigarette smoking, and increased BMI were found to be independently associated with abnormal elevation of liver transaminase as shown in Tables 2 and 4. Moreover, all these factors except increased BMI were also found to be associated with liver cirrhosis diagnosed through ultrasonography, which fur-ther increased the credibility of this study. Therefore, we concluded that biochemical dysfunction of liver may be independently affected by the above risk factors, includ-ing betel chewinclud-ing. Tables 3 and 4 seemed to indicate that persistent elevation of liver transaminases could be an early sign of chronic inflammation that might result in the liver cirrhosis. But we should not make too strong infer-ence because of the limited number of cases and lack of biopsy proof.

Therefore, we concluded that biochemical dysfunction of liver may be independently affected by the above risk fac-tors, including betel chewing. Efforts to reduce the preva-lence of liver disease in Aboriginal should, therefore, include efforts to increase quitting of the betel habit. The above findings deserve to examine possible causal mechanism between betel quid chewing and liver injury. Areca nut was reported to immunologically suppress body defense to HBV/HCV infection [34] and increase the risk of toxic hepatitis[31,32], which might be related to other reactive oxygen adducts formed as a result of habitual betel chewing [35,36]. An alternative explanation might be the high proportion (up to 37.5%) of betel quids con-taminated by aflatoxin [37], which is a well-documented hepatotoxin [38,39]. Further studies are needed to deter-mine which components of betel quids may be responsi-ble for liver damage are now required.

Although Safrole, listed as a carcinogen by the Environ-mental Protection Administration, USA, have been iso-lated from areca nut [34], the phenolic compounds in betel leaf might be antimutagenic [40,41] or possibly pro-Table 4: Adjusted odds ratio(OR) and 95%CI (confidence

interval) from multiple logistic regression for risk factors of cirrhosis of liver diagnosed by ultrasonography

Variables No. of liver cirrhosis/total OR (95%CI) No. of Cases 41/1382 (3.0%) Ethnic group Non-Aboriginal 7/398 (1.8%) 1.0 Aboriginal 34/984 (3.5%) 1.8(1.4–3.6) Alcohol drinking Never 2/681(0.3%) 1.0 Former 6/101(5.9%) 1.6(1.3–4.6) Current 33/600(5.5%) 2.1(1.5–3.5) Cigarette smoking Never 9/892(1.0%) 1.0 Former 2/49(4.1%) 1.3(0.6–10.7) Current 30/441(6.8%) 1.8(1.1–2.7) Betel quid chewing

No 19/679(3.5%) 1.0 Yes 22/703(2.2%) 1.7(1.2–2.3) Gender Female 5/732(0.7%) 1.0 Male 36/650(5.5%) 1.5(1.2–3.9) BMI <=25 26/852(3.1%) 1.0 >25 15/530(2.8%) 0.9(0.6–1.7) HBV/HCV -/- 21/1020(2.1%) 1.0 +/- 18/300(6.0%) 1.9(0.4–12.8) -/+ 1/32(3.1%) 2.2(1.4–4.7) +/+ 1/3(33.3%) 5.4(0.2–7.6) +:positive; -:negative OR: odds ratio

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tective against carcinogens [42]. Thus, it is difficult to hypothesize. As there were 86% smokers and 75% drink-ers in Chinese betel chewdrink-ers [14], the possible mecha-nisms and interactions among smoking, drinking, and betel chewing deserved further studies on the develop-ment of liver cirrhosis.

Conclusion

The shortened life expectancy in Aboriginal people of Tai-wan has long been noticed since the early 1980's [1]. The issue has attracted public concern after democratization of Taiwan. Recently, the government of Taiwan has put a lot of efforts to improve Aboriginal health for the reason of equity and justice. The funding of this study was part of such efforts to determine the major risk factors and prev-alence rates of various diseases. The next moves will not only further increase coverage rates of National Health Insurance, improve health manpower and accessibility for healthcare of Aboriginal community in remote area, but also provide programs for reduction in betel chewing rates in Aboriginals to effectively prevent liver diseases

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

YC and PH joined in the design of the study. CF and TJ car-ried out the studies, participated in the sequence align-ment and data collection. CF and PH conducted data analysis, and CF drafted the manuscript. JD supervised to complete the data analysis and helped to finalize the man-uscript. All of the authors read and approve the manu-script.

Acknowledgements

This study was supported in part by grants from the National Health Research Institutes (Grant No. NHRI-EX96-9204pp; NHRI-CN-PD9611P) and from the Department of Health, Executive Yuan, Taiwan.

References

1. Ko YC, Liu BH, Hsieh SF: Issues on aboriginal health in Taiwan. Kaohsiung J Med Sci 1994, 10:337-351.

2. Zola IK: Pathways to the doctor-from person to patient. Soc Sci Med 1973, 7(9):677-689.

3. Cooper-Patrick L, Crum RM, Ford DE: Characteristics of patients

with major depression who received care in general medical and specialty mental health settings. Med Care 1994, 32(1):15-24.

4. Gilbert GH: Access to and patterns of use of oral health care

among elderly veterans. Med Care 1995, 33(11 Suppl):NS78-89.

5. Consensus 1990: Census report of the Republic of China in Taiwan. Department of population. Taipei, Taiwan.

6. Bellwood P: The Austronesian dispersal and the origin of

lan-guages. Sci Am 1991, 265:70-75.

7. Strogatz DS: Use of medical care for chest pain: differences

between blacks and whites. Am J Public Health 1990, 80(3):290-294.

8. Chung DC, Ko YC, Chen CJ, Wu CC, Chen ER, Liaw YF, Hwang SJ:

Seroepidemiological studies on hepatitis B and D viruses infection among five ethnic groups in southern Taiwan. J Med

Virol 1988, 26(4):411-418.

9. Beasley RP, Hwang LY, Lin CC, Leu ML, Stevens CE, Szmuness W, Chen KP: Incidence of hepatitis B virus infections in preschool

children in Taiwan. J Infect Dis 1982, 146(2):198-204.

10. Wu JS, Lu CF, Chou WH, Chen HY, Lee HF, Wu YC, Lin SY: High

prevalence of hepatitis C virus infection in aborigines in Tai-wan. Jpn J Med Sci Biol 1992, 45(4):165-174.

11. Hwu HG, Yeh YL, Wang JD, Yeh EK: Alcoholism among Taiwan

aborigines defined by the Chinese Diagnostic Interview Schedule: a comparison with alcoholism among Chinese.

Acta Psychiatr Scand 1990, 82(5):374-380.

12. Chen WJ, Loh EW, Hsu YP, Cheng AT: Alcohol dehydrogenase

and aldehyde dehydrogenase genotypes and alcoholism among Taiwanese aborigines. Biol Psychiatry 1997,

41(6):703-709.

13. Norton SA: Betel: consumption and consequences. J Am Acad Dermatol 1998, 38(1):81-88.

14. Ko YC, Chiang TA, Chang SJ, Hsieh SF: Prevalence of betel quid

chewing habit in Taiwan and related sociodemographic fac-tors. J Oral Pathol Med 1992, 21(6):261-264.

15. Nelson BS, Heischober B: Betel nut: a common drug used by

naturalized citizens from India, Far East Asia, and the South Pacific Islands. Ann Emerg Med 1999, 34(2):238-243.

16. IARC: Betel-quid and areca-nut chewing and some

areca-nut-derived nitrosamines. Volume 85. IARC Monogr Eval Carcinog

Risks Hum; 2004.

17. Ko YC, Huang YL, Lee CH, Chen MJ, Lin LM, Tsai CC: Betel quid

chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan. Journal of Oral Pathological

Med-icine 1995, 24(10):450-453.

18. Lu CT, Yen YY, Ho CS, Ko YC, Tsai CC, Hsieh CC, Lan SJ: A

case-control study of oral cancer in Changhua County, Taiwan.

Journal of Oral Pathological Medicine 1996, 25(5):245-248.

19. Lee KW, Kuo WR, Tsai SM, Wu DC, Wang WM, Fang FM, Chiang FY, Ho KY, Wang LF, Tai CF, et al.: Different impact from betel quid,

alcohol and cigarette: risk factors for pharyngeal and laryn-geal cancer. International Journal of Cancer 2005, 117(5):831-836.

20. Yang YH, Lee HY, Tung S, Shieh TY: Epidemiological survey of

oral submucous fibrosis and leukoplakia in aborigines of Tai-wan. Journal of Oral Pathological Medicine 2001, 30(4):213-219.

21. Lee CH, Ko YC, Huang HL, Chao YY, Tsai CC, Shieh TY, Lin LM: The

precancer risk of betel quid chewing, tobacco use and alco-hol consumption in oral leukoplakia and oral submucous fibrosis in southern Taiwan. British Journal of Cancer 2003, 88(3):366-372.

22. Lin HH, Wang LY, Shaw CK, Cheng ML, Chung WK, Chiang HJ, Lin TY, Chen CJ: Combined effects of chronic hepatitis virus

infec-tions and substance-use habits on chronic liver diseases in Taiwanese aborigines. J Formos Med Assoc 2002,

101(12):826-834.

23. Tsai JF, Jeng JE, Chuang LY, Ho MS, Ko YC, Lin ZY, Hsieh MY, Chen SC, Chuang WL, Wang LY, et al.: Habitual betel quid chewing as

a risk factor for cirrhosis: a case-control study. Medicine

(Balti-more) 2003, 82(5):365-372.

24. Tsai JF, Jeng JE, Chuang LY, Ho MS, Ko YC, Lin ZY, Hsieh MY, Chen SC, Chuang WL, Wang LY, et al.: Habitual betel quid chewing

and risk for hepatocellular carcinoma complicating cirrhosis.

Medicine (Baltimore) 2004, 83(3):176-187.

25. Tung TH, Chiu YH, Chen LS, Wu HM, Boucher BJ, Chen TH: A

pop-ulation-based study of the association between areca nut chewing and type 2 diabetes mellitus in men (Keelung Com-munity-based Integrated Screening programme No. 2).

Dia-betologia 2004, 47(10):1776-1781.

26. Yang MJ, Chung TC, Hsu TY, Ko YC: Betel quid chewing and risk

of adverse birth outcomes among aborigines in eastern Tai-wan. J Toxicol Environ Health A 2001, 64(6):465-472.

27. Nair J, Ohshima H, Friesen M, Croisy A, Bhide SV, Bartsch H:

Tobacco-specific and betel nut-specific N-nitroso com-pounds: occurrence in saliva and urine of betel quid chewers and formation in vitro by nitrosation of betel quid.

Carcinogen-esis 1985, 6(2):295-303.

28. Caldwell SH, Oelsner DH, Iezzoni JC, Hespenheide EE, Battle EH, Driscoll CJ: Cryptogenic cirrhosis: clinical characterization

and risk factors for underlying disease. Hepatology 1999, 29(3):664-669.

29. Corrao G, Torchio P, Zambon A, D'Amicis A, Lepore AR, di Orio F:

(8)

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tors for liver cirrhosis: a case-control study. The Provincial Group for the study of Chronic Liver Disease. Ann Epidemiol

1998, 8(3):154-159.

30. Du CL, Wang JD: Increased morbidity odds ratio of primary

liver cancer and cirrhosis of the liver among vinyl chloride monomer workers. Occup Environ Med 1998, 55(8):528-532.

31. Sarma AB, Chakrabarti J, Chakrabarti A, Banerjee TS, Roy D, Mukher-jee D, MukherMukher-jee A: Evaluation of pan masala for toxic effects

on liver and other organs. Food Chem Toxicol 1992, 30(2):161-163.

32. Singh A, Rao AR: Evaluation of the modifying influence of

are-canut on the garlic-modulated hepatic detoxication system enzymes, sulfhydryl content, and lipid peroxidation in mice.

Teratog Carcinog Mutagen 1995, 15(3):127-134.

33. Yang PM, Huang GT, Lin JT, Sheu JC, Lai MY, Su IJ, Hsu HC, Chen DS, Wang TH, Sung JL: Ultrasonography in the diagnosis of benign

diffuse parenchymal liver diseases: a prospective study. J

For-mos Med Assor 1988, 87(10):966-977.

34. Shahabuddin S, Rao AR, Mustafa AS: Effect of arecoline on the

humoral & cell mediated immune responses in mice. Indian J

Exp Biol 1980, 18(12):1493-1494.

35. Houglum K, Filip M, Witztum JL, Chojkier M: Malondialdehyde and

4-hydroxynonenal protein adducts in plasma and liver of rats with iron overload. J Clin Invest 1990, 86(6):1991-1998.

36. Tsukamoto H: Oxidative stress, antioxidants, and alcoholic

liver fibrogenesis. Alcohol 1993, 10(6):465-467.

37. Raisuddin S, Misra JK: Aflatoxin in betel nut and its control by

use of food preservatives. Food Addit Contam 1991, 8(6):707-712.

38. Bhat RV: Aflatoxin and liver injury. Trop Gastroenterol 1996,

17(3):153-160.

39. Krishnamachari KA, Bhat RV, Nagarajan V, Tilak TB: Hepatitis due

to aflatoxicosis. An outbreak in Western India. Lancet 1975, 1(7915):1061-1063.

40. Amonkar AJ, Nagabhushan M, D'Souza AV, Bhide SV:

Hydroxy-chavicol: a new phenolic antimutagen from betel leaf. Food

Chem Toxicol 1986, 24(12):1321-1324.

41. Padma PR, Amonkar AJ, Bhide SV: Antimutagenic effects of betel

leaf extract against the mutagenicity of two tobacco-specific N-nitrosamines. Mutagenesis 1989, 4(2):154-156.

42. Padma PR, Lalitha VS, Amonkar AJ, Bhide SV: Anticarcinogenic

effect of betel leaf extract against tobacco carcinogens.

Can-cer Lett 1989, 45(3):195-202.

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數據

Table 2 summarizes the results of multiple logistic regres- regres-sion modeling by using a backward stepwise procedure to choose the major risk factors (p value &lt; 0.001) of  abnor-mal biochemical liver function
Table 2: Frequency, odds ratio(OR) and 95%CI (confidence interval) for different risk factors of abnormal biochemical liver function  estimated from multiple regression logistic model after adjustment for age, gender, and education level
Table 4: Adjusted odds ratio(OR) and 95%CI (confidence  interval) from multiple logistic regression for risk factors of  cirrhosis of liver diagnosed by ultrasonography

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