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Prevalence of hepatitis B and hepatitis C in patients with chronic schizophrenia living in institutions
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Journal of the Chinese Medical Association 75 (2012) 275e280 www.jcma-online.com
Original Article
Prevalence of hepatitis B and hepatitis C in patients with chronic schizophrenia living in institutions Chia-Chun Hung a, El-Wui Loh b, Tsung-Ming Hu c, Hsien-Jane Chiu d, Hung-Chieh Hsieh c, Chin-Hong Chan a, Tsuo-Hung Lan a,* b
a Department of Psychiatry, Taichung Veterans General Hospital, Taichung, Taiwan, ROC Division of Mental Health and Substance Abuse Research, National Health Research Institute, Taipei, Taiwan, ROC c Department of Psychiatry, Yu-Li Hospital, Hualien, Taiwan, ROC d Jianan Mental Hospital, Executive Yuan Psychiatry, Tainan, Taiwan, ROC
Received September 27, 2011; accepted January 5, 2012
Abstract Background: Preventing and managing hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is an important public health issue worldwide, and Taiwan is one of the countries where viral hepatitis is most endemic. Previous studies have shown that patients with serious mental illnesses have a higher risk for hepatitis infection. We investigated the prevalence of HBV and HCV among institutionalized patients with chronic schizophrenia in Taiwan. Methods: A total of 590 patients were recruited into the study. HBV surface antigen, HCV antibody, and liver function were determined for all participants. Results: The seroprevalence of HBV surface antigen was 10.4% (males 12.6%, females 7.0%), and that of anti-HCV was 1.9% (males 2.6%, females 0.8%). Conclusion: Our study showed that the prevalences of HBV and HCV among institutionalized patients with chronic schizophrenia were no higher than the prevalences in the general population in Taiwan. The commodious environment and medical resources of the hospital where the patients were living might have prevented an elevation of HBV and HCV infection in those with schizophrenia, supplementing the continuing benefits from the HBV vaccination that was introduced in 1984. Copyright Ó 2012 Elsevier Taiwan LLC and the Chinese Medical Association. All rights reserved. Keywords: hepatitis B; hepatitis C; prevalence; schizophrenia
1. Introduction July 28, 2011 was designated by the World Health Organization (WHO) as the first annual World Hepatitis Day, in order to increase global awareness of the problem of hepatitisdnearly one out of every three people in the world has been infected by hepatitis virus. According to the most recent WHO report, approximately 2 billion people worldwide * Corresponding author. Dr. Tsuo-Hung Lan, Department of Psychiatry, Taichung Veterans General Hospital, 160, Section 3, Chung-Kang Road, Taichung 407, Taiwan, ROC. E-mail address: [email protected] (T.-H. Lan).
have been infected with hepatitis B virus (HBV), and an estimated 600,000 people die every year due to the acute or chronic consequences of hepatitis B. At any given time, about 130e170 million people are chronically infected with hepatitis C virus (HCV), and more than 350,000 people die from hepatitis C-related liver diseases each year.1 The statistics suggests that there is a further need to prevent, screen for, and intervene early cases of HBV and HCV infection. The prevalence of chronic HBV infection is about 5% worldwide, but this figure varies substantially between regions. Infection rates are low (0.1e2.0%) in the United States and Western Europe, intermediate (2.0e8.0%) in Mediterranean countries and Japan, and high (8.0e20.0%) in
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South-East Asia and the sub-Saharan regions.2 HCV infection is of epidemic proportions worldwide. Countries with high rates of chronic infection are Egypt (22%), Pakistan (4.8%), and China (3.2%).1 Taiwan is among the countries where the infection is highly prevalent, with 15e20% of the general population suffering from chronic HBV infection3e6 and an estimated 4.4% of the general population with chronic HCV infection.6 Previous studies have reported a higher infection rate with HBV and HCV in specific groups, such as parenteral drug users, male homosexuals, immunosuppressed patients, those with hemophilia, and patients undergoing dialysis. A higher incidence of hepatitis has also been identified in healthcare workers, ambulance personnel, teachers, and staff in institutions such as retirement homes and institutions for the intellectual disability7e9 and those suffering serious mental illness.10e12 Associated with their psychiatric impairment, persons with severe mental illness are at an increased risk for several co-morbid conditions, including substance use disorder.13 They are also likely to be overrepresented in highrisk categories for infections such as HBV and HCV.11 However, few studies have focused on HBV and HCV infection rates among institutionalized patients with severe mental illness, especially in a country with a high prevalence of HBV. In an attempt to further assist in the prevention and control of such an important public health concern, we conducted a study to investigate the prevalence of HBV and HCV infection in subjects with and without impaired liver function among institutionalized schizophrenic patients in Taiwan. 2. Methods 2.1. Subjects In this study, 590 patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text revision (DSM-IV-TR)14 criteria for schizophrenia were recruited from the Yuli Veterans Hospital, a facility that is affiliated to one of the largest mental hospitals in Taiwan. The Yuli Veterans Hospital is operated under the concept of therapeutic communities.15 The details of the research and the procedures were fully explained to all the subjects, and written informed consent was obtained from all patients. The study was approved by the Institutional Research Board of Yuli Veterans Hospital. 2.2. Demographic data As shown in Table 1, a total of 590 schizophrenic patients were recruited for this study, all of whom were inpatients at Yuli Veterans Hospital. Of those patients, 203 (34.4%) were 40e49 years of age. The mean age of the study subjects was 42.5 10.67 years (range 20e83 years). Overall, 348 (59.0%) patients were men and 242 (41.0%) were women. Most patients (34.4%) were senior high school graduates. All study subjects had been hospitalized for more than 1 year at Yuli Veterans Hospital.
Table 1 The demographic data of schizophrenia patients in this study. Demographic data Gender Age level
Education years
History of alcohol use Current alcohol use History of cigarette use Current cigarette use
Female Male 20e29 30e39 40e49 50e59 60e69 70 Elementary school Junior high school Senior high school College Others or illiteracy No Yes No Yes No Yes No Yes
n
%
242 348 34 186 203 126 33 8 110 148 198 70 50 421 168 583 3 305 284 322 265
41.0 59.0 5.8 31.5 34.4 21.4 5.6 1.4 19.1 25.7 34.4 12.2 8.7 71.5 28.5 99.5 0.5 51.8 48.2 54.9 45.1
2.3. Serological analysis Blood samples were collected in April 2000 and examined in the clinical laboratories of Yuli Veterans Hospital. HBV surface antigen (HBsAg) was tested using a microparticle enzyme immunoassay (MEIA) method (AxSYM HBsAg (V2); No.7A40 -22). Antibodies to HCV were assessed in serum using MEIA (Abbott AxSYM HCV version 3.0; No.3B44-20, Abbott Laboratories Limited, Diagnostic Division, Abbott House, Norden Road, Maidenhead, Berkshire, SL6 4XF, England). Initially reactive assays were repeated in duplicate. At least two reactive results constituted a final result of an HCV-positive status. Results suggested an overall confirmation rate of more than 99% of MEIA-positive tests. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also tested, levels below 0.75 mkat/L being considered to be within the normal range. 2.4. Statistical methods Distributions of HBV and HCV carriers and noninfected subjects in terms of age, gender, and liver function test results were examined using c2 tests for categorical variables. All statistical tests were two-sided, conducted at a significance level of 0.05. All analyses were performed using SPSS software version 15 (International Business Machines Corporation (IBM), Armonk, New York, United States). 3. Results 3.1. HBV prevalence The results of HBsAg testing are shown in Table 2. The test reports were available for 570 out of 590 patients. The
C.-C. Hung et al. / Journal of the Chinese Medical Association 75 (2012) 275e280 Table 2 The sero-prevalence of HBsAg in chronic institutionally resided schizophrenia patients.
277
Table 3 The sero-prevalence of anti-HCV in chronic institutionally resided schizophrenia patients.
Hepatitis B surface antigen p value Negative
Gender
Female Male Age 20e29 30e39 40e49 50e59 60e69 70 Education level Elementary school Junior high school Senior high school College Others or illiteracy Aspartate < 0.75 aminotransferase 0.75 level (mkat/L) Alanine < 0.75 aminotransferase 0.75 level (mkat/L) History of No alcohol use Yes Current No alcohol use Yes History of No cigarette use Yes Current No cigarette use Yes
Anti-hepatitis C virus
Positive
Negative
n
%
n
%
212 299 30 154 179 109 32 7 94 119 174 65 46 495 16
41.5 58.5 5.9 30.1 35.0 21.3 6.3 1.4 18.9 23.9 34.9 13.1 9.2 96.9 3.1
16 43 4 24 21 8 1 1 12 21 20 4 2 57 2
27.1 72.9 6.8 40.7 35.6 13.6 1.7 1.7 20.3 35.6 33.9 6.8 3.4 96.6 3.4
415 95
81.4 18.6
40 19
67.8 32.2
0.022
368 142 505 3 264 246 277 231
72.2 27.8 99.4 0.6 51.8 48.2 54.5 45.5
38 21 59 0 28 31 31 28
64.4 35.6 100.0 0.0 47.5 52.5 52.5 47.5
0.274
0.035 0.353
0.149
0.709
1.000 0.625 0.879
seroprevalence rate for HBsAg was 10.4%, including 43 males (12.6%) and 16 females (7.0%). Among the patients positive for HBsAg, there was no significant difference in age, educational level, or history of alcohol or cigarette use, except for gender. Among the patients positive for HBsAg, 72.9% were males and 27.1% were females ( p ¼ 0.035). Two patients (3.4%) with elevated AST and 19 patients (32.2%) with elevated ALT were noted. There was no difference in AST between patients who tested positive or negative for HbsAg ( p ¼ 0.709), but disproportionally high levels of ALT were noted in patients who tested positive for HbsAg ( p ¼ 0.022). 3.2. HCV prevalence The result of anti-HCV testing is shown in Table 3. AntiHCV test reports were available for 588 of the 590 patients. The seroprevalence rate of anti-HCV was 1.9%, including nine males (2.6%) and two females (0.8%). There was no significant difference in the demographic data among patients who were anti-HCV positive. There was a higher proportion of abnormal AST (81.8%, p ¼ 0.042) and ALT (72.7%, p < 0.0001) levels among anti-HCV-positive patients compared to anti-HCV-negative patients. Three of 11 patients with antiHCV-positive readings had impaired liver function with levels above two folds the normal upper range (data not shown).
Gender
Female Male Age 20e29 30e39 40e49 50e59 60e69 70 Education level Elementary school Junior high school Senior high school College Others or illiteracy Aspartate < 0.75 aminotransferase 0.75 level (mkat/L) Alanine < 0.75 aminotransferase 0.75 level (mkat/L) History of No alcohol use Yes Current No alcohol use Yes History of No cigarette use Yes Current No cigarette use Yes
p value
Positive
n
%
n
%
240 337 33 180 200 125 32 7 110 142 194 68 49 554 16
41.6 58.4 5.7 31.2 34.7 21.7 5.5 1.2 19.5 25.2 34.5 12.1 8.7 97.2 2.8
2 9 1 4 3 1 1 1 0 5 3 2 1 9 2
18.2 81.8 9.1 36.4 27.3 9.1 9.1 9.1 0.0 45.5 27.3 18.2 9.1 81.8 18.2
464 105
81.5 18.5
3 8
27.3 72.7
<0.0001
411 165 570 3 303 273 318 256
71.4 28.6 99.5 0.5 52.6 47.4 55.4 44.6
9 2 11 0 2 9 4 7
81.8 18.2 100.0 0.0 18.2 81.8 36.4 63.6
0.737
0.136 0.249
0.341
0.042
1.000 0.050 0.235
3.3. HBV and HCV co-infection There was only one patient with concurrent HBV and HCV infection (0.2%).
4. Discussion Previous epidemiological data indicate that patients with serious mental illnesses are at increased risk for HBV and HCV infection.10e12 According to current guidelines,9,16 all patients with chronic HBV and HCV infection, especially those with impaired liver function, should be assessed to determine whether they might benefit from therapy. In our study, no patient with chronic HBV or HCV infection ever underwent this treatment evaluation. The burden of HBV and HCV infections and the consequences may thus be underestimated. The prevalence of HBV in Taiwan ranges from 10% to 17.3%, according to different surveys (Table 4).6,17e24 In our study, the prevalence of HBV among patients with schizophrenia appeared to be lower than that in the general population. The likelihood that an HBV infection will become chronic depends upon the age at which a person becomes infected, with young children infected with HBV being most likely to develop chronic hepatitis.1,25 Most patients with
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Table 4 Comparison of the prevalence in the general population in Taiwan. Trial (year)
HBV
HCV
Current study (2000) Chen and Sung (1978)20 Wu et al (1991)24 Sun et al (1999)41 Merican et al (2000)17 Lin et al (2000)23 Sun et al (2001)47 Wang et al (2002)18 Yang et al (2003)16 Chen et al (2007)6 Chen et al (2007)19 Huang et al ((2008)21 Lai et al (2009)22
10.4% 15.0% d d > 10.0% 14.8% d 13.8% d 17.3% 12.8% d 6.6e15.1%
1.8% d 0.1e34.1% Mean 2.28% (1.60e19.60%) 1.0% 16.7% 5.4% 17.0% 3.9% 4.4% d 2.8% d
Notes Only HBV prevalence High variation between groups Only HCV prevalence; high variation between towns Difference between ethnicities Only HCV prevalence Data for the southern Taiwanese town where infection is most prevalent 1996e2005; large scale survey Only HBV prevalence Only HCV prevalence Only HBV prevalence
HBV ¼ hepatitis B virus; HCV ¼ hepatitis C virus.
chronic hepatitis B in Taiwan have been infected via perinatal transmission that occurred before the implementation of the national hepatitis B vaccination program in 1984.25 Acute HBV infection may cause acute hepatic failure and mortality. Several studies have reported that HBV contributes to 7e32% of the etiology of acute hepatic failure.26e29 It is reasonable to imply that a proportion of schizophrenic patients may have died from acute hepatic failure during acute infection or reactivation, and thus have not been included in our statistics. In addition, long-term hospitalization may prevent patients with chronic schizophrenia from exposure to risky behaviors, such as tattooing, intravenous drug abuse, inappropriate sexual contact, ear piercing, etc., thus reducing the risk for HBV infection. Furthermore, the prevalence of hepatitis in schizophrenic patients might have been reduced by the vaccination program that has been promoted by the Department of Health in Taiwan since 1984. The program began with free-of-charge vaccination of newborn babies, and then gradually included older people. Eventually, all citizens with HBsAg-negative serum, including institutionalized patients with mental illness, were offered the vaccination.30,31 Consequently, the prevalence rate of hepatitis B has declined in Taiwan in recent years.9,13,16,32e39 This decline in prevalence rate may also be seen in institutionalized patients with serious mental illness. The prevalence of HCV varies among studies in normal populations. Merican et al reported the lowest HCV prevalence of 1.00%;17 Sun et al reported an HCV prevalence of 1.60e19.60%, with a mean prevalence of 2.28%.40 The prevalence of HCV in patients in our study is similar to that seen in other surveys in Taiwan during the first decade of the 21st century (Table 4). Wang et al reported the highest prevalence of approximately 17% in a town in southern Taiwan with the most elevated HCV prevalence, whereas Lin et al reported a 16.7% prevalence rate of HCV in Eastern Taiwan, with a range of 3.6e27.5% among different aboriginal villages.23 HCV is less efficiently transmitted by single small-dose percutaneous exposures (e.g., accidental needlestick injuries)41,42 or by mucosal exposures to blood or serum-derived fluids (e.g., birth to an infected mother, sexual contact with an
infected partner).11,41,43 Transmission of HCV is mainly caused by cross-contamination from reused needles and syringes, multiple-use medication vials, infusion bags, and injection drug use devices.44e46 As to how this affects chronically institutionalized patients with schizophrenia, HCV transmission may be lower in this population due to heightened levels of medical attention given to the patients and their less risky behaviors, as mentioned above. The prevalences of HBV and HCV in our study were no higher than the prevalences in other studies investigating psychiatric patients (Table 5). Said et al reported an HBV prevalence of 7.29% in patients with serious mental illness.12 Chaudhury et al reported a prevalence rate of 12% of HBV in mentally ill patients, which was 5.5 times higher than the equivalent prevalence in the matched controls.8 Rosenberg et al reported a prevalences of 23.4% for HBV and 19.6% for HCV in serious mentally ill patients, values that were five and 11 times higher than those in the overall general population, respectively.11 Sixty-five per cent of patients mentioned in Rosenbery et al’s study were recruited from the outpatient clinic, and 75% of patients with HCV infection were selfreported injection drug users. These authors concluded that elevated rates within several risk categories may reflect the poverty, risky environments, and overall poor health and medical care that are common in many people with severe mental illness. On the other hand,
Table 5 Comparison of prevalence in serious mental illness. HBV
HCV
Current study (2000) Said et al (2001)12
10.35% 7.29%
1.87% NA
Chaudhury et al (1994)8
12.00%
NA
Rosenberg et al (2001)11
23.40%
19.60%
HBV ¼ hepatitis B virus; HCV ¼ hepatitis C virus.
Jordan; only HBV prevalence India; only HBV prevalence; 5.5 times the matched control USA; five and 11 times the overall general population, respectively
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patients with schizophrenia in the Yuli Veterans Hospital were housed in open dormitories with medical professionals on duty, with extensive space provided for leisure and physical activities.15 The protective, medically supervised environment may keep these patients from risky behaviors and thus reduce the rates of infectious disease (Tables 4 and 5).6,8,11,12,16e24,41,47 In conclusion, our study showed that the prevalences of HBV and HCV among institutionalized patients with chronic schizophrenia were no higher than those in the general population. The patients recruited in this study were all permanent residents of the Yuli Veterans Hospital and were considered to be chronically ill.15 These patients came from not only neighboring cities, but also the entire country, and could be representative of the patient population with chronic schizophrenia throughout Taiwan. The commodious environment and available medical resources of the hospital where the patients resided might have prevented an elevation of HBV and HCV infection rates, which is worth further exploration. References 1. Hepatits factsheets. Geneva: World Health Organization; 2011. 2. Liaw YF, Chu CM. Hepatitis B virus infection. Lancet 2009;373:582e92. 3. Shepard CW, Simard EP, Finelli L, Fiore AE, Bell BP. Hepatitis B virus infection: epidemiology and vaccination. Epidemiol Rev 2006;28: 112e25. 4. Sung JL, Chen DS, Lai MY, Wang TH, Wang CY, Yu JY, et al. Hepatitis B e antigen and antibody in asymptomatic Chinese with hepatitis B surface antigenemia in Taiwan. Gastroenterol Jpn 1982;17:341e6. 5. Lin DB, Wang HM, Lee YL, Ling UP, Changlai SP, Chen CJ. Immune status in preschool children born after mass hepatitis B vaccination program in Taiwan. Vaccine 1998;16:1683e7. 6. Chen CH, Yang PM, Huang GT, Lee HS, Sung JL, Sheu JC. Estimation of seroprevalence of hepatitis B virus and hepatitis C virus in Taiwan from a large-scale survey of free hepatitis screening participants. J Formos Med Assoc 2007;106:148e55. 7. Wright R, McCollum RW, Klatskin G. Australia antigen in acute and chronic liver disease. Lancet 1969;2:117e21. 8. Chaudhury S, Chandra S, Augustine M. Prevalence of Australia antigen (HBsAg) in institutionalised patients with psychosis. Br J Psychiatry 1994;164:542e3. 9. Sherman M, Shafran S, Burak K, Doucette K, Wong W, Girgrah N, et al. Management of chronic hepatitis B: consensus guidelines. Can J Gastroenterol 2007;21(Suppl):5Ce24C. 10. Goldberg RW. Hepatitis and HIV screening, education, and treatment for adults with serious mental illness. Gen Hosp Psychiatry 2004;26:167e8. 11. Rosenberg SD, Goodman LA, Osher FC, Swartz MS, Essock SM, Butterfield MI, et al. Prevalence of HIV, hepatitis B, and hepatitis C in people with severe mental illness. Am J Public Health 2001;91:31e7. 12. Said WM, Saleh R, Jumaian N. Prevalence of hepatitis B virus among chronic schizophrenia patients. East Mediterr Health J 2001;7:526e30. 13. Wassermann EM. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5e7, 1996. Electroencephalogr Clin Neurophysiol 1998;108:1e16. 14. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed, text revision (DSM-IV-TR). Arlington, VA: American Psychiatric Association; 2000. 15. Lin CY, Huang AL, Minas H, Cohen A. Mental hospital reform in Asia: the case of Yuli Veterans Hospital, Taiwan. Int J Ment Health Syst 2009;3:1.
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16. Sherman M, Shafran S, Burak K, Doucette K, Wong W, Girgrah N, et al. Management of chronic hepatitis C: consensus guidelines. Can J Gastroenterol 2007;21(Suppl):25Ce34C. 17. Merican I, Guan R, Amarapuka D, Alexander MJ, Chutaputti A, Chien RN, et al. Chronic hepatitis B virus infection in Asian countries. J Gastroenterol Hepatol 2000;15:1356e61. 18. Wang CS, Chang TT, Yao WJ, Chou P. Comparison of hepatitis B virus and hepatitis C virus prevalence and risk factors in a community-based study. Am J Trop Med Hyg 2002;66:389e93. 19. Chen CC, Yen CH, Wu WY, Hu SW, Chen SC, Bell WR, et al. Epidemiology of hepatitis B virus infection among young adults in Taiwan, China after public vaccination program. Chin Med J (Engl) 2007;120: 1155e8. 20. Chen DS, Sung JL. Hepatitis B virus infection and chronic liver disease in Taiwan. Acta Hepatogastroenterol (Stuttg) 1978;25:423e30. 21. Huang CF, Huang JF, Dai CY, Yu ML, Lu SN, Hsieh MY, et al. Changing prevalence of hepatitis C virus infection among teenagers in an endemic area in Taiwan. Trans R Soc Trop Med Hyg 2008;102:929e34. 22. Lai HW, Hsiung HY, Tai JJ, Chen SI, Chang HC, Chen TH. Ethnicspecific prevalence of hepatitis B/C virus infection in Pin-Jen, Taiwan. Ethn Dis 2009;19:384e9. 23. Lin HH, Li YH, Yu JH, Wang YW, Lua AC, Huang LC, et al. Ethnic and geographic variations in the prevalence of hepatitis A, B and C among aboriginal villages in Hualien, Taiwan. Infection 2000;28: 205e8. 24. Wu JS, Lu CF, Liu WT, Lin SY. Prevalence of antibodies to hepatitis C virus (anti-HCV) in different populations in Taiwan. Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi 1991;24:55e60. 25. Acute hepatitis B. Taiwan: Centers for Disease Control; 2009. 26. Brandsaeter B, Hockerstedt K, Friman S, Ericzon BG, Kirkegaard P, Isoniemi H, et al. Fulminant hepatic failure: outcome after listing for highly urgent liver transplantation e 12 years experience in the nordic countries. Liver Transpl 2002;8:1055e62. 27. Escorsell A, Mas A, de la Mata M. Acute liver failure in Spain: analysis of 267 cases. Liver Transpl 2007;13:1389e95. 28. Ichai P, Samuel D. Epidemiology of liver failure. Clin Res Hepatol Gastroenterol 2011;35:610e7. 29. Williams R, Wendon J. Indications for orthotopic liver transplantation in fulminant liver failure. Hepatology 1994;20:S5e10. 30. Chien YC, Jan CF, Kuo HS, Chen CJ. Nationwide hepatitis B vaccination program in Taiwan: effectiveness in the 20 years after it was launched. Epidemiol Rev 2006;28:126e35. 31. Chen DS, Hsu NH, Sung JL, Hsu TC, Hsu ST, Kuo YT, et al. A mass vaccination program in Taiwan against hepatitis B virus infection in infants of hepatitis B surface antigen-carrier mothers. JAMA 1987;257:2597e603. 32. Kao JH, Chen DS. Global control of hepatitis B virus infection. Lancet Infect Dis 2002;2:395e403. 33. Hsu HM, Lu CF, Lee SC, Lin SR, Chen DS. Seroepidemiologic survey for hepatitis B virus infection in Taiwan: the effect of hepatitis B mass immunization. J Infect Dis 1999;179:367e70. 34. Ni YH, Chang MH, Huang LM, Chen HL, Hsu HY, Chiu TY, et al. Hepatitis B virus infection in children and adolescents in a hyperendemic area: 15 years after mass hepatitis B vaccination. Ann Intern Med 2001; 135:796e800. 35. Chen CJ, Wang LY, Yu MW. Epidemiology of hepatitis B virus infection in the Asia-Pacific region. J Gastroenterol Hepatol 2000;15(Suppl):E3e6. 36. Chen DS. Public health measures to control hepatitis B virus infection in the developing countries of the Asia-Pacific region. J Gastroenterol Hepatol 2000;15(Suppl):E7e10. 37. Huang K, Lin S. Nationwide vaccination: a success story in Taiwan. Vaccine 2000;18(Suppl):S35e8. 38. Chen HL, Chang MH, Ni YH, Hsu HY, Lee PI, Lee CY, et al. Seroepidemiology of hepatitis B virus infection in children: ten years of mass vaccination in Taiwan. JAMA 1996;276:906e8. 39. Hsu HM, Chen DS, Chuang CH, Lu JC, Jwo DM, Lee CC, et al. Efficacy of a mass hepatitis B vaccination program in Taiwan. Studies on 3464
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infants of hepatitis B surface antigen-carrier mothers. JAMA 1988;260: 2231e5. 40. Sun CA, Chen HC, Lu CF, You SL, Mau YC, Ho MS, et al. Transmission of hepatitis C virus in Taiwan: prevalence and risk factors based on a nationwide survey. J Med Virol 1999;59:290e6. 41. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. Centers for Disease Control and Prevention. MMWR Recomm Rep 1998;47:1e39. 42. Puro V, Petrosillo N, Ippolito G. Risk of hepatitis C seroconversion after occupational exposures in health care workers. Italian Study Group on Occupational Risk of HIV and Other Bloodborne Infections. Am J Infect Control 1995;23:273e7.
43. Terrault NA. Sexual activity as a risk factor for hepatitis C. Hepatology 2002;36(Suppl):S99e105. 44. Hagan H, Thiede H, Weiss NS, Hopkins SG, Duchin JS, Alexander ER. Sharing of drug preparation equipment as a risk factor for hepatitis C. Am J Public Health 2001;91:42e6. 45. Williams IT, Perz JF, Bell BP. Viral hepatitis transmission in ambulatory health care settings. Clin Infect Dis 2004;38:1592e8. 46. Alter MJ. Epidemiology of hepatitis C virus infection. World J Gastroenterol 2007;13:2436e41. 47. Sun CA, Chen HC, Lu SN, Chen CJ, Lu CF, You SL, et al. Persistent hyperendemicity of hepatitis C virus infection in Taiwan: the important role of iatrogenic risk factors. J Med Virol 2001;65:30e4.
Journal of the Chinese Medical Association 75 (2012) 275e280 www.jcma-online.com
Original Article
Prevalence of hepatitis B and hepatitis C in patients with chronic schizophrenia living in institutions Chia-Chun Hung a, El-Wui Loh b, Tsung-Ming Hu c, Hsien-Jane Chiu d, Hung-Chieh Hsieh c, Chin-Hong Chan a, Tsuo-Hung Lan a,* b
a Department of Psychiatry, Taichung Veterans General Hospital, Taichung, Taiwan, ROC Division of Mental Health and Substance Abuse Research, National Health Research Institute, Taipei, Taiwan, ROC c Department of Psychiatry, Yu-Li Hospital, Hualien, Taiwan, ROC d Jianan Mental Hospital, Executive Yuan Psychiatry, Tainan, Taiwan, ROC
Received September 27, 2011; accepted January 5, 2012
Abstract Background: Preventing and managing hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is an important public health issue worldwide, and Taiwan is one of the countries where viral hepatitis is most endemic. Previous studies have shown that patients with serious mental illnesses have a higher risk for hepatitis infection. We investigated the prevalence of HBV and HCV among institutionalized patients with chronic schizophrenia in Taiwan. Methods: A total of 590 patients were recruited into the study. HBV surface antigen, HCV antibody, and liver function were determined for all participants. Results: The seroprevalence of HBV surface antigen was 10.4% (males 12.6%, females 7.0%), and that of anti-HCV was 1.9% (males 2.6%, females 0.8%). Conclusion: Our study showed that the prevalences of HBV and HCV among institutionalized patients with chronic schizophrenia were no higher than the prevalences in the general population in Taiwan. The commodious environment and medical resources of the hospital where the patients were living might have prevented an elevation of HBV and HCV infection in those with schizophrenia, supplementing the continuing benefits from the HBV vaccination that was introduced in 1984. Copyright Ó 2012 Elsevier Taiwan LLC and the Chinese Medical Association. All rights reserved. Keywords: hepatitis B; hepatitis C; prevalence; schizophrenia
1. Introduction July 28, 2011 was designated by the World Health Organization (WHO) as the first annual World Hepatitis Day, in order to increase global awareness of the problem of hepatitisdnearly one out of every three people in the world has been infected by hepatitis virus. According to the most recent WHO report, approximately 2 billion people worldwide * Corresponding author. Dr. Tsuo-Hung Lan, Department of Psychiatry, Taichung Veterans General Hospital, 160, Section 3, Chung-Kang Road, Taichung 407, Taiwan, ROC. E-mail address: [email protected] (T.-H. Lan).
have been infected with hepatitis B virus (HBV), and an estimated 600,000 people die every year due to the acute or chronic consequences of hepatitis B. At any given time, about 130e170 million people are chronically infected with hepatitis C virus (HCV), and more than 350,000 people die from hepatitis C-related liver diseases each year.1 The statistics suggests that there is a further need to prevent, screen for, and intervene early cases of HBV and HCV infection. The prevalence of chronic HBV infection is about 5% worldwide, but this figure varies substantially between regions. Infection rates are low (0.1e2.0%) in the United States and Western Europe, intermediate (2.0e8.0%) in Mediterranean countries and Japan, and high (8.0e20.0%) in
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South-East Asia and the sub-Saharan regions.2 HCV infection is of epidemic proportions worldwide. Countries with high rates of chronic infection are Egypt (22%), Pakistan (4.8%), and China (3.2%).1 Taiwan is among the countries where the infection is highly prevalent, with 15e20% of the general population suffering from chronic HBV infection3e6 and an estimated 4.4% of the general population with chronic HCV infection.6 Previous studies have reported a higher infection rate with HBV and HCV in specific groups, such as parenteral drug users, male homosexuals, immunosuppressed patients, those with hemophilia, and patients undergoing dialysis. A higher incidence of hepatitis has also been identified in healthcare workers, ambulance personnel, teachers, and staff in institutions such as retirement homes and institutions for the intellectual disability7e9 and those suffering serious mental illness.10e12 Associated with their psychiatric impairment, persons with severe mental illness are at an increased risk for several co-morbid conditions, including substance use disorder.13 They are also likely to be overrepresented in highrisk categories for infections such as HBV and HCV.11 However, few studies have focused on HBV and HCV infection rates among institutionalized patients with severe mental illness, especially in a country with a high prevalence of HBV. In an attempt to further assist in the prevention and control of such an important public health concern, we conducted a study to investigate the prevalence of HBV and HCV infection in subjects with and without impaired liver function among institutionalized schizophrenic patients in Taiwan. 2. Methods 2.1. Subjects In this study, 590 patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text revision (DSM-IV-TR)14 criteria for schizophrenia were recruited from the Yuli Veterans Hospital, a facility that is affiliated to one of the largest mental hospitals in Taiwan. The Yuli Veterans Hospital is operated under the concept of therapeutic communities.15 The details of the research and the procedures were fully explained to all the subjects, and written informed consent was obtained from all patients. The study was approved by the Institutional Research Board of Yuli Veterans Hospital. 2.2. Demographic data As shown in Table 1, a total of 590 schizophrenic patients were recruited for this study, all of whom were inpatients at Yuli Veterans Hospital. Of those patients, 203 (34.4%) were 40e49 years of age. The mean age of the study subjects was 42.5 10.67 years (range 20e83 years). Overall, 348 (59.0%) patients were men and 242 (41.0%) were women. Most patients (34.4%) were senior high school graduates. All study subjects had been hospitalized for more than 1 year at Yuli Veterans Hospital.
Table 1 The demographic data of schizophrenia patients in this study. Demographic data Gender Age level
Education years
History of alcohol use Current alcohol use History of cigarette use Current cigarette use
Female Male 20e29 30e39 40e49 50e59 60e69 70 Elementary school Junior high school Senior high school College Others or illiteracy No Yes No Yes No Yes No Yes
n
%
242 348 34 186 203 126 33 8 110 148 198 70 50 421 168 583 3 305 284 322 265
41.0 59.0 5.8 31.5 34.4 21.4 5.6 1.4 19.1 25.7 34.4 12.2 8.7 71.5 28.5 99.5 0.5 51.8 48.2 54.9 45.1
2.3. Serological analysis Blood samples were collected in April 2000 and examined in the clinical laboratories of Yuli Veterans Hospital. HBV surface antigen (HBsAg) was tested using a microparticle enzyme immunoassay (MEIA) method (AxSYM HBsAg (V2); No.7A40 -22). Antibodies to HCV were assessed in serum using MEIA (Abbott AxSYM HCV version 3.0; No.3B44-20, Abbott Laboratories Limited, Diagnostic Division, Abbott House, Norden Road, Maidenhead, Berkshire, SL6 4XF, England). Initially reactive assays were repeated in duplicate. At least two reactive results constituted a final result of an HCV-positive status. Results suggested an overall confirmation rate of more than 99% of MEIA-positive tests. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also tested, levels below 0.75 mkat/L being considered to be within the normal range. 2.4. Statistical methods Distributions of HBV and HCV carriers and noninfected subjects in terms of age, gender, and liver function test results were examined using c2 tests for categorical variables. All statistical tests were two-sided, conducted at a significance level of 0.05. All analyses were performed using SPSS software version 15 (International Business Machines Corporation (IBM), Armonk, New York, United States). 3. Results 3.1. HBV prevalence The results of HBsAg testing are shown in Table 2. The test reports were available for 570 out of 590 patients. The
C.-C. Hung et al. / Journal of the Chinese Medical Association 75 (2012) 275e280 Table 2 The sero-prevalence of HBsAg in chronic institutionally resided schizophrenia patients.
277
Table 3 The sero-prevalence of anti-HCV in chronic institutionally resided schizophrenia patients.
Hepatitis B surface antigen p value Negative
Gender
Female Male Age 20e29 30e39 40e49 50e59 60e69 70 Education level Elementary school Junior high school Senior high school College Others or illiteracy Aspartate < 0.75 aminotransferase 0.75 level (mkat/L) Alanine < 0.75 aminotransferase 0.75 level (mkat/L) History of No alcohol use Yes Current No alcohol use Yes History of No cigarette use Yes Current No cigarette use Yes
Anti-hepatitis C virus
Positive
Negative
n
%
n
%
212 299 30 154 179 109 32 7 94 119 174 65 46 495 16
41.5 58.5 5.9 30.1 35.0 21.3 6.3 1.4 18.9 23.9 34.9 13.1 9.2 96.9 3.1
16 43 4 24 21 8 1 1 12 21 20 4 2 57 2
27.1 72.9 6.8 40.7 35.6 13.6 1.7 1.7 20.3 35.6 33.9 6.8 3.4 96.6 3.4
415 95
81.4 18.6
40 19
67.8 32.2
0.022
368 142 505 3 264 246 277 231
72.2 27.8 99.4 0.6 51.8 48.2 54.5 45.5
38 21 59 0 28 31 31 28
64.4 35.6 100.0 0.0 47.5 52.5 52.5 47.5
0.274
0.035 0.353
0.149
0.709
1.000 0.625 0.879
seroprevalence rate for HBsAg was 10.4%, including 43 males (12.6%) and 16 females (7.0%). Among the patients positive for HBsAg, there was no significant difference in age, educational level, or history of alcohol or cigarette use, except for gender. Among the patients positive for HBsAg, 72.9% were males and 27.1% were females ( p ¼ 0.035). Two patients (3.4%) with elevated AST and 19 patients (32.2%) with elevated ALT were noted. There was no difference in AST between patients who tested positive or negative for HbsAg ( p ¼ 0.709), but disproportionally high levels of ALT were noted in patients who tested positive for HbsAg ( p ¼ 0.022). 3.2. HCV prevalence The result of anti-HCV testing is shown in Table 3. AntiHCV test reports were available for 588 of the 590 patients. The seroprevalence rate of anti-HCV was 1.9%, including nine males (2.6%) and two females (0.8%). There was no significant difference in the demographic data among patients who were anti-HCV positive. There was a higher proportion of abnormal AST (81.8%, p ¼ 0.042) and ALT (72.7%, p < 0.0001) levels among anti-HCV-positive patients compared to anti-HCV-negative patients. Three of 11 patients with antiHCV-positive readings had impaired liver function with levels above two folds the normal upper range (data not shown).
Gender
Female Male Age 20e29 30e39 40e49 50e59 60e69 70 Education level Elementary school Junior high school Senior high school College Others or illiteracy Aspartate < 0.75 aminotransferase 0.75 level (mkat/L) Alanine < 0.75 aminotransferase 0.75 level (mkat/L) History of No alcohol use Yes Current No alcohol use Yes History of No cigarette use Yes Current No cigarette use Yes
p value
Positive
n
%
n
%
240 337 33 180 200 125 32 7 110 142 194 68 49 554 16
41.6 58.4 5.7 31.2 34.7 21.7 5.5 1.2 19.5 25.2 34.5 12.1 8.7 97.2 2.8
2 9 1 4 3 1 1 1 0 5 3 2 1 9 2
18.2 81.8 9.1 36.4 27.3 9.1 9.1 9.1 0.0 45.5 27.3 18.2 9.1 81.8 18.2
464 105
81.5 18.5
3 8
27.3 72.7
<0.0001
411 165 570 3 303 273 318 256
71.4 28.6 99.5 0.5 52.6 47.4 55.4 44.6
9 2 11 0 2 9 4 7
81.8 18.2 100.0 0.0 18.2 81.8 36.4 63.6
0.737
0.136 0.249
0.341
0.042
1.000 0.050 0.235
3.3. HBV and HCV co-infection There was only one patient with concurrent HBV and HCV infection (0.2%).
4. Discussion Previous epidemiological data indicate that patients with serious mental illnesses are at increased risk for HBV and HCV infection.10e12 According to current guidelines,9,16 all patients with chronic HBV and HCV infection, especially those with impaired liver function, should be assessed to determine whether they might benefit from therapy. In our study, no patient with chronic HBV or HCV infection ever underwent this treatment evaluation. The burden of HBV and HCV infections and the consequences may thus be underestimated. The prevalence of HBV in Taiwan ranges from 10% to 17.3%, according to different surveys (Table 4).6,17e24 In our study, the prevalence of HBV among patients with schizophrenia appeared to be lower than that in the general population. The likelihood that an HBV infection will become chronic depends upon the age at which a person becomes infected, with young children infected with HBV being most likely to develop chronic hepatitis.1,25 Most patients with
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Table 4 Comparison of the prevalence in the general population in Taiwan. Trial (year)
HBV
HCV
Current study (2000) Chen and Sung (1978)20 Wu et al (1991)24 Sun et al (1999)41 Merican et al (2000)17 Lin et al (2000)23 Sun et al (2001)47 Wang et al (2002)18 Yang et al (2003)16 Chen et al (2007)6 Chen et al (2007)19 Huang et al ((2008)21 Lai et al (2009)22
10.4% 15.0% d d > 10.0% 14.8% d 13.8% d 17.3% 12.8% d 6.6e15.1%
1.8% d 0.1e34.1% Mean 2.28% (1.60e19.60%) 1.0% 16.7% 5.4% 17.0% 3.9% 4.4% d 2.8% d
Notes Only HBV prevalence High variation between groups Only HCV prevalence; high variation between towns Difference between ethnicities Only HCV prevalence Data for the southern Taiwanese town where infection is most prevalent 1996e2005; large scale survey Only HBV prevalence Only HCV prevalence Only HBV prevalence
HBV ¼ hepatitis B virus; HCV ¼ hepatitis C virus.
chronic hepatitis B in Taiwan have been infected via perinatal transmission that occurred before the implementation of the national hepatitis B vaccination program in 1984.25 Acute HBV infection may cause acute hepatic failure and mortality. Several studies have reported that HBV contributes to 7e32% of the etiology of acute hepatic failure.26e29 It is reasonable to imply that a proportion of schizophrenic patients may have died from acute hepatic failure during acute infection or reactivation, and thus have not been included in our statistics. In addition, long-term hospitalization may prevent patients with chronic schizophrenia from exposure to risky behaviors, such as tattooing, intravenous drug abuse, inappropriate sexual contact, ear piercing, etc., thus reducing the risk for HBV infection. Furthermore, the prevalence of hepatitis in schizophrenic patients might have been reduced by the vaccination program that has been promoted by the Department of Health in Taiwan since 1984. The program began with free-of-charge vaccination of newborn babies, and then gradually included older people. Eventually, all citizens with HBsAg-negative serum, including institutionalized patients with mental illness, were offered the vaccination.30,31 Consequently, the prevalence rate of hepatitis B has declined in Taiwan in recent years.9,13,16,32e39 This decline in prevalence rate may also be seen in institutionalized patients with serious mental illness. The prevalence of HCV varies among studies in normal populations. Merican et al reported the lowest HCV prevalence of 1.00%;17 Sun et al reported an HCV prevalence of 1.60e19.60%, with a mean prevalence of 2.28%.40 The prevalence of HCV in patients in our study is similar to that seen in other surveys in Taiwan during the first decade of the 21st century (Table 4). Wang et al reported the highest prevalence of approximately 17% in a town in southern Taiwan with the most elevated HCV prevalence, whereas Lin et al reported a 16.7% prevalence rate of HCV in Eastern Taiwan, with a range of 3.6e27.5% among different aboriginal villages.23 HCV is less efficiently transmitted by single small-dose percutaneous exposures (e.g., accidental needlestick injuries)41,42 or by mucosal exposures to blood or serum-derived fluids (e.g., birth to an infected mother, sexual contact with an
infected partner).11,41,43 Transmission of HCV is mainly caused by cross-contamination from reused needles and syringes, multiple-use medication vials, infusion bags, and injection drug use devices.44e46 As to how this affects chronically institutionalized patients with schizophrenia, HCV transmission may be lower in this population due to heightened levels of medical attention given to the patients and their less risky behaviors, as mentioned above. The prevalences of HBV and HCV in our study were no higher than the prevalences in other studies investigating psychiatric patients (Table 5). Said et al reported an HBV prevalence of 7.29% in patients with serious mental illness.12 Chaudhury et al reported a prevalence rate of 12% of HBV in mentally ill patients, which was 5.5 times higher than the equivalent prevalence in the matched controls.8 Rosenberg et al reported a prevalences of 23.4% for HBV and 19.6% for HCV in serious mentally ill patients, values that were five and 11 times higher than those in the overall general population, respectively.11 Sixty-five per cent of patients mentioned in Rosenbery et al’s study were recruited from the outpatient clinic, and 75% of patients with HCV infection were selfreported injection drug users. These authors concluded that elevated rates within several risk categories may reflect the poverty, risky environments, and overall poor health and medical care that are common in many people with severe mental illness. On the other hand,
Table 5 Comparison of prevalence in serious mental illness. HBV
HCV
Current study (2000) Said et al (2001)12
10.35% 7.29%
1.87% NA
Chaudhury et al (1994)8
12.00%
NA
Rosenberg et al (2001)11
23.40%
19.60%
HBV ¼ hepatitis B virus; HCV ¼ hepatitis C virus.
Jordan; only HBV prevalence India; only HBV prevalence; 5.5 times the matched control USA; five and 11 times the overall general population, respectively
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patients with schizophrenia in the Yuli Veterans Hospital were housed in open dormitories with medical professionals on duty, with extensive space provided for leisure and physical activities.15 The protective, medically supervised environment may keep these patients from risky behaviors and thus reduce the rates of infectious disease (Tables 4 and 5).6,8,11,12,16e24,41,47 In conclusion, our study showed that the prevalences of HBV and HCV among institutionalized patients with chronic schizophrenia were no higher than those in the general population. The patients recruited in this study were all permanent residents of the Yuli Veterans Hospital and were considered to be chronically ill.15 These patients came from not only neighboring cities, but also the entire country, and could be representative of the patient population with chronic schizophrenia throughout Taiwan. The commodious environment and available medical resources of the hospital where the patients resided might have prevented an elevation of HBV and HCV infection rates, which is worth further exploration. References 1. Hepatits factsheets. Geneva: World Health Organization; 2011. 2. Liaw YF, Chu CM. Hepatitis B virus infection. Lancet 2009;373:582e92. 3. Shepard CW, Simard EP, Finelli L, Fiore AE, Bell BP. Hepatitis B virus infection: epidemiology and vaccination. Epidemiol Rev 2006;28: 112e25. 4. Sung JL, Chen DS, Lai MY, Wang TH, Wang CY, Yu JY, et al. Hepatitis B e antigen and antibody in asymptomatic Chinese with hepatitis B surface antigenemia in Taiwan. Gastroenterol Jpn 1982;17:341e6. 5. Lin DB, Wang HM, Lee YL, Ling UP, Changlai SP, Chen CJ. Immune status in preschool children born after mass hepatitis B vaccination program in Taiwan. Vaccine 1998;16:1683e7. 6. Chen CH, Yang PM, Huang GT, Lee HS, Sung JL, Sheu JC. Estimation of seroprevalence of hepatitis B virus and hepatitis C virus in Taiwan from a large-scale survey of free hepatitis screening participants. J Formos Med Assoc 2007;106:148e55. 7. Wright R, McCollum RW, Klatskin G. Australia antigen in acute and chronic liver disease. Lancet 1969;2:117e21. 8. Chaudhury S, Chandra S, Augustine M. Prevalence of Australia antigen (HBsAg) in institutionalised patients with psychosis. Br J Psychiatry 1994;164:542e3. 9. Sherman M, Shafran S, Burak K, Doucette K, Wong W, Girgrah N, et al. Management of chronic hepatitis B: consensus guidelines. Can J Gastroenterol 2007;21(Suppl):5Ce24C. 10. Goldberg RW. Hepatitis and HIV screening, education, and treatment for adults with serious mental illness. Gen Hosp Psychiatry 2004;26:167e8. 11. Rosenberg SD, Goodman LA, Osher FC, Swartz MS, Essock SM, Butterfield MI, et al. Prevalence of HIV, hepatitis B, and hepatitis C in people with severe mental illness. Am J Public Health 2001;91:31e7. 12. Said WM, Saleh R, Jumaian N. Prevalence of hepatitis B virus among chronic schizophrenia patients. East Mediterr Health J 2001;7:526e30. 13. Wassermann EM. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5e7, 1996. Electroencephalogr Clin Neurophysiol 1998;108:1e16. 14. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed, text revision (DSM-IV-TR). Arlington, VA: American Psychiatric Association; 2000. 15. Lin CY, Huang AL, Minas H, Cohen A. Mental hospital reform in Asia: the case of Yuli Veterans Hospital, Taiwan. Int J Ment Health Syst 2009;3:1.
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