Differing Characteristics of Hepatitis B and C Risk Factors Among Elders in a Rural Area in Taiwan

Transcription

1 Journal of Gerontology: MEDICAL SCIENCES 1998, Vol. 53A, No. 2, MI07-M111 Copyright 1998 by The Gemntological Society of America Differing Characteristics of Hepatitis B and C Risk Factors Among Elders in a Rural Area in Taiwan Chong-Shan Wang, 1 Ting-Tsung Chang, 2 and Pesus Chou 3 'A-Lein Community Health Center, Taiwan, Republic of China. 2 Division of Gastroenterology, Department of Internal Medicine, National Cheng Kung University, Tainan, Taiwan. Community Medicine Research Center and Institute of Public Health, National Yang-Ming University, Taipei, Taiwan. Background. Both hepatitis B and C are major health concerns in Taiwan. The goal of this study was to determine how risk factors for hepatitis B and C differed in this study population. It was also hoped that the data might help determine how age and place of residence affect hepatitis risk factors. Methods. Complete serum and hepatitis marker analysis (HBsAg and AntiHCV) was done for 282 individuals over 65 years old. Of these, 254 were interviewed for risk factor analysis. Results. Of the 282 subjects, 8.2% were HBsAg+, 27.3% were AntiHCV+, and 3.2% were both HBsAg+ and Anti- HCV+. AntiHCV+ subjects were more likely than AntiHCV-subjects to have had frequent medical injections, odds ratio (OR) = 2.94, 95% confidence interval (CI) (1.68, 5.12), and it was the only independent risk factor for determining AntiHCV+, OR = 3.26, 95% CI (1.85, 6.11) (N = 254). The AntiHCV+ group had higher alanine and asparate aminotransferase levels but lower cholesterol and triglyceride levels than AntiHCV- and HBsAg+ groups (p <.0001). Abnormal ALT existed in 40.3% of AntiHCV+ and 10.7% of AntiHCV- cases. ALT was associated with AntiHCV and sex, although abnormal AST was only associated with AntiHCV. Conclusions. AntiHCV was closely related with frequent medical injections and was the primary risk factor for abnormal ALT and AST levels in this study population. It appears that frequent medical injections are an important risk factor because of the previously common habit of reusing syringes. This is of major concern to elders in Taiwan because of their much greater likelihood of repeated exposure. LTHOUGH there are reports that hepatoma may be \ related to ethnicity, sex, age, alcohol consumption, viral hepatitis, aflatoxin, cirrhosis, smoking, and exposure to chemicals, the most prevalent risk factor for hepatoma is hepatitis B and C infection (1,2). About 80% of hepatoma cases in Taiwan have hepatitis B, and the relative risk of getting hepatoma was 98.4 times higher among those with hepatitis B than among those without it (3). The number of AntiHCV+ hepatoma cases has gradually increased in recent decades. In both Japan (4) and some European countries (1), 70% of hepatoma cases are also AntiHCV+. Although hepatitis B and hepatitis C are transmitted by blood or serum, their preferred transmission routes vary according to age, geography, and living habits. Between 85 and 90% of neonates are infected and become hepatitis B carriers if their mothers are hepatitis B carriers (5). Hepatitis C infection is rarely transmitted through the placenta or breast feeding (1). Most hepatitis C carriers were infected as adults, and 50-90% of acute infections become chronic hepatitis C cases (6). According to earlier studies, the main risk factors for HCV infection are blood transfusion, intravenous drug use, alcoholism, hemodialysis, acupuncture, sexual transmission, and sporadic community acquisition (1,7-9). Clinical experiences of the first author suggested that another risk factor might be at play in this community: from medical injection with reused syringes. Therefore, a secondary goal of this study was to determine if frequent injections were a risk factor for either hepatitis B or C infection. It was discovered in a previous study by the author (10) that hepatoma is the leading cause of cancer mortality in A- Lein, Taiwan, with 43.2% of all cancer deaths from due to hepatoma. Furthermore, government statistics show that the male mortality rate from hepatoma in the region is 81.3 in every 100,000 people, which is 2.5 times higher than the average for Taiwan in 1992 (11). Hepatitis B and C are both major risk factors for hepatoma, and it was hoped that this study might shed light on the causes for the unusually large instances of hepatoma in A-Lein. The prevalence of HBsAg+ in adults is 15-20% in Taiwan (12), and the prevalence of AntiHCV+ in adults is approximately 2.5% (13), but the prevalence of HBsAg+ and AntiHCV+ in elderly people is rarely studied. The purpose of this research project is to study the prevalence and risk factors of hepatitis B or C in elders of this community, in the hope that it might increase the understanding of the causes of the high hepatoma mortality rate and help prevent further hepatitis transmission. METHODS A-Lein is located in Kaohsiung County in southern Taiwan and has a population of approximately 30,000. In 1995 there were 2,047 people over 65 years of age (6.8% of the whole community); in that year 330 elderly individuals came to the A-Lein Community Health Center to receive free medical examinations sponsored by the Kaohsiung County Government (150 males and 180 females, 16.0% M107

2 M108 WANG ETAL. response rate). Of the 330, 282 completed the complete battery of tests, which included HBsAg, AntiHCV, body mass index (BMI), alanine aminotransferase (ALT), asparate aminotransferase (AST), cholesterol, triglyceride, total protein, albumin, uric acid, hemoglobin, blood urea nitrogen (BUN), and creatinine. Because all sample and data collection was done in the course of routine medical examinations requested by the examinees, informed consent specific to this study was not sought. Of the 282, 254 were also interviewed and asked several questions regarding hepatitis risk factors. Questions were asked about acupuncture, blood transfusion, frequent medical injections, intravenous drug use, and alcoholism. Both alcoholic dependence and frequent heavy use were defined as alcoholism. Alcoholic dependence and abuse were defined according to DSM-3 and DSM- 3R (14,15). Alcohol abuse was defined as regular, abnormal consumption for at least one month and alcoholrelated impairment of social or occupational functioning. Alcohol dependence further requires tolerance or withdrawal symptoms (16). Frequent medical injections was defined as having at least 6 injections per year for at least 2 years in a row in the past by a practitioner who reused syringes. We arbitrarily created this definition because we could find no studies of frequent medical injection in the literature to use as a precedent. Actually, medical injection usage patterns were quite clear in this study population; the substantial majority of those classified as receiving frequent medical injections actually averaged > 1 injection per month for at least 2 years. Abbot EIA 2nd generation (Abbot Diagnostics, Chicago, IL) tests were used to determine AntiHCV, and FUJI- RPHA tests (reverse-passive hemagglutination) (Fujirebio, Tokyo, Japan) were used to determine HBsAg. Both tests were performed according to recommendations of the manufacturers. Stata software release 3.5 (Computing Resources Center, Santa Monica, CA) was used for biostatistic calculations. The Mest was used for comparing the result of physiological and biochemical tests in HBsAg and AntiHCV. The chisquare test was used in analyzing the significant risk factors for HBsAg and AntiHCV. Multiple logistic regression analysis was used for determining the independent factors which affect ALT level, AST level, HBsAg, and AntiHCV. RESULTS The prevalence of AntiHCV+ among the study population was 27.3%, but the prevalence of HBsAg+ was much lower, only 8.2% (p <.0001); 3.2% of the study population were both AntiHCV+ and HBsAg+. The prevalence rates of hepatitis B and C were not significantly associated with age (p =.09) or sex (data not shown). Risk factor analysis demonstrated that 64.5% of Anti- HCV+ cases had frequent medical injections, which was significantly higher than among AntiHCV- cases, odds ratio (OR) = 2.94, 95% confidence interval (CI) (1.68, 5.12), p = There were no significant differences between the AntiHCV+ and AntiHCV- groups in regards to acupuncture, blood transfusion, and alcoholism (p >.05). Also, there were no significant differences in risk factor ratios between HBsAg+ and HBsAg- cases (Table 1). According to multivariate logistic regression analysis, the only risk factor for determining AntiHCV results was frequent medical injections [OR = 3.25, 95% CI (1.83, 5.77)]. Acupuncture, blood transfusion, age, and sex were not significant determinants for AntiHCV or HBsAg+ (Table 2). The AntiHCV+ group had higher ALT and AST levels but lower cholesterol and triglyceride levels than the Anti- HCV- group, p <.001. There were no significant differences in physiological and biochemical results between the HBsAg+ and the group that was both AntiHCV- and HBsAg-. ALT, AST, and triglyceride levels in those with HBsAg+ and AntiHCV+ dual infections were similar to those who were only AntiHCV+, but not to those who were only HBsAg+, p <.05 (Table 3). There were no significant differences between the four groups (HBsAg+/AntiHCV+, HBsAg+/AntiHCV- HBsAg-/AntiHCV+, and HBsAg+ AntiHCV-) in age, BMI, total protein, albumin, uric acid, hemoglobin, BUN, and creatinine. Of the AntiHCV+ cases, 40.3% had abnormal ALT levels and 48.1% had abnormal AST levels 40), but the corresponding figures for the Anti-HCV- group were only 10.7% and 13.2%; 58.5% of those with abnormal ALT levels and 68.5% of those with abnormal AST levels were AntiHCV+. Correspondingly, only 20.1% of those with normal ALT levels and 17.5% of those with normal AST were AntiHCV+. Of those with ALT levels greater than 40, 54% were HBsAg-/AntiHCV+, 34% were HBsAg-/Anti- HCV-, and 4% were HBsAg+/AntiHCV-. Multivariate logistic regression analysis showed that AntiHCV+ and sex Table 1. Four Hepatitis Results Groupings With Number and Percentage According to Four Potential Risk Factors Hepatitis Status HBsAg-/AntiHCV-(W = 168) HBsAg+/AntiHCV- (N = 10) HBsAg-/AntiHCV+ (JV = 67) HBsAg+/AntiHCV+(/V = 9) Acupuncture 29 (17.3) 4 (40.0) 10 (14.9) Frequent Medical Injections 64 (38.1) 4 (40.0) 42 (62.7)* 7 (77.8)* Blood Transfusions 20 (11.9) 1 (10.0) 7 (10.4) 2 (22.2) Alcoholism 5 (3.0) 3 (4.5) *The only significant risk factor was frequent medical injections. Note the difference between the AntiHCV- and AntiHCV+ (*) groups, OR = 2.94, 95%CI(1.68,5.12),p =.001.

3 HEPATITIS B AND C IN TAIWAN M109 (female) are the only independent factors that determine abnormal ALT. BMI and age were the factors for HBsAg. Abnormal AST is not affected by sex. Therefore, multiple logistic regression shows that the only significant determinant for ALT and AST is AntiHCV status (Table 4). DISCUSSION The average age and sex ratio of the study population was similar to that of the corresponding segment of the larger population. There were no cases of hemodialysis, intravenous drug use, or severe illness among the examinees, and little alcoholism; therefore, the health status of the study population was not worse than the average of their peers. Those with a history of liver problems would Table 2. Multiple Logistic Regression Analysis of HBsAg and AntiHCV Risk Factors Risk Factor Acupuncture Medical injection Blood transfusion Age Sex (male vs female) AntiHCV (N = 253) OR 95% CI * Note: OR = odds ratio; CI = confidence interval. ALT AST Cholesterol Triglyceride HBsAg (N = 251) OR 95% CI have undergone testing at a hospital and were therefore much less likely to come to the A-Lein Community Health Center for screening. Therefore, high-risk aggregates of liver diseases were missed, and it is very possible that the prevalence of AntiHCV and HBsAg in the community have been underestimated. Abnormal ALT and AST levels were mainly affected by AntiHCV and not by HBsAg, age, sex, or BMI. Other studies also found that abnormal liver transaminases were mainly affected by AntiHCV (17) and that 40-50% of Anti- HCV+ cases had abnormal ALT levels (7). The AntiHCV+ group in this study had significantly lower cholesterol and triglyceride serum levels than the HBsAg+ group or the HBsAg-/AntiHCV- group. This may be because AntiHCV+ cases among elders are often combined with more severe chronic hepatitis, cirrhosis, or hepatoma (18), which results in decreased liver cell synthesis of these two materials (19). Regretfully, the number of male study participants was not large enough to make a firm conclusion in this matter. AntiHCV+ prevalence in this study is 27.2% (77/283), which is much higher than other studies in Taiwan (20). This is probably because the people in our study population were all age 65 and above and therefore had a much greater likelihood of exposure (possibly from frequent medical injections, as discussed below) than the rest of the population. This study found an HBsAg+ prevalence rate of only 8%, although approximately 15-20% of adults in Taiwan are HBsAg+ (12) with an annual clearance rate of 1% (21). An important, probable reason why the level of HBsAg+ individuals is relatively low in this group is that many HBsAg+ Table 3. Physiological and Biochemical Results From the Examinations of 282 Elders From A-Lein, Taiwan. HBsAg-ZAntiHCV- HBsAg+/AntiHCV- HBsAg-/AntiHCV+ HBsAg+/AntiHCV+ («= 191) (n = 14) (n = 68) («= 9) 22.7 ± ± ± ± ± ± ± ± ±73.0*** 55. 7± 53.9*** ±41.6*** ±65.6* 44.7 ± 26.7*** 45.8 ±22.7*** ± ± 28.9* Note: ALT = alanine aminotransferase; AST = asparate aminotransferase. *.01 < p <.05; ***p <.001 (These refer to the Mest results of the HBsAg-/anti-HCV+ group or HBsAg+/anti-HCV+ group compared to the HBsAg-/anti-HCV- group. The following were found not significant: age, albumin, BMI, BUN, creatinine, hemoglobin, total protein, uric acid.) Table 4. Logistic Regression Analysis of ALT (^ 40 vs < 40) and AST Values fe 40 vs < 40) (N = 282). ALT AST OR 95% CI OR 95% CI AntiHCV * * HBsAg Sex (male vs female) Age ^.05* BMI Note: ALT = alanine aminotransferase; AST = asparate aminotransferase; OR = odds ratio; CI = confidence interval. Statistically significant (p <.05).

4 MHO WANG ETAL. individuals may have already developed hepatoma and died prior to reaching age 65. Some studies have shown that the average age of mortality in HBsAg+ hepatoma cases was about 55 years, but for AntiHCV+ hepatoma cases it is about 65 years (22,23). The prevalence of AntiHCV+ is 3.5 times higher than HBsAg+ in this study population, which might also explain why male hepatoma in this area is 2.5 times higher than the Taiwan average (83 vs 33 per 100,000) (22,23). In Taiwan, about % of hepatoma patients were HBsAg+ and % of those were AntiHCV+. This is of greater concern considering that Taiwan as a whole has very high average hepatoma mortality rates (24). It is extremely doubtful that any subjects had received hepatitis B by way of a hepatitis B vaccine, because use of this vaccine in Taiwan was commonly used starting only 10 years ago, and then only in children. ALT and AST levels and the risk factors for HBsAg+ and AntiHCV+ dual infections in the same individual were similar to those of AntiHCV+ but not to those of HBsAg+. This may be due to super infection of asymptomatic HBsAg+ with AntiHCV+, which then progresses to the characteristics of AntiHCV+ (9). In this study only 11.8% of AntiHCV+ cases had undergone blood transfusions. This was not significantly different from the AntiHCV- group and much lower than other studies in which up to 60% of AntiHCV+ cases had undergone blood transfusions (9). This suggests that other important risk factors are present for this community. The most unusual finding in this study was that 64.5% of the AntiHCV+ group had frequent medical injections. This was much more than the AntiHCV- group, OR = 2.94, 95% CI (1.68, 5.12). Frequent medical injections was the only significant risk factor for AntiHCV as determined by multivariate logistic regression,/? < This suggests that this study population received hepatitis C infection mainly through medical injections, in which case hepatitis C may have been spread by health care workers (25) and might therefore be considered an iatrogenic disease. There is a possibility that for some of these cases the cause and effect are reversed, i.e., that because they were AntiHCV+ they were not healthy in general and required additional medical treatment. We did not consider this an important factor for this study because the vast majority of cases in which frequent medical injections took place were for very common maladies, mostly cold, flu, and myofacial pain, which in no way correspond to being AntiHCV+. The reuse of needles with sterilization only by boiling water was common practice well into the 1980s, particularly in rural areas of Taiwan and among unlicensed medical practitioners. It most likely was at this time or earlier that a large number of people in this community were infected. This mechanism of HCV infection is similar to intravenous injection among drug users, for whom Anti- HCV+ prevalence corresponds positively with the duration and frequency of injection (8). With age, the frequency of medical conditions treated with injections increases, which might further explain the disproportionally high prevalence of AntiHCV+ in this study population. Regretfully, it is still a common belief among people in this rural community that receiving an injection to quickly recover from any sort of minor ailment is "good medicine," and doctors here are generally willing to oblige them. Furthermore, in order to save money, some people still receive this sort of treatment from nonlicensed practitioners, such as pharmacists or quack practitioners, who are more likely to boil and reuse syringes. Therefore, some risk of further iatrogenic infection remains. It is hoped that this study will further discourage abuse of medical injections and the practice of receiving injections from nonlicensed practitioners. In conclusion, this study demonstrates that frequent medical injections can be a primary cause of AntiHCV+. This information should prove useful for health education, prevention, and strategic intervention. This study also compares the characteristics of HBsAg+ and AntiHCV+, which is also useful for further follow-up and study of mortality related to viral hepatitis among the elderly population. The prevalence of HBsAg+ appears to decrease and AntiHCV+ increase with age in a community in a high hepatitis B endemic area such as Taiwan. 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