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ARTICLE IN PRESS Digestive and Liver Disease xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld
Liver, Pancreas and Biliary Tract
Seroprevalence and risk factors for hepatitis C virus infection among blood donors in Serbia: A multicentre study Nikola Mitrovic a,∗ , Dragan Delic a,b , Ljiljana Markovic-Denic b,c , Milica Jovicic d , Natasa Popovic a , Ksenija Bojovic a,b , Jasmina Simonovic Babic a,b , Neda Svirtlih a,b a
Clinic for Infectious and Tropical Disease, Belgrade, Serbia University of Belgrade, Faculty of Medicine, Belgrade, Serbia c Institute of Epidemiology, Belgrade, Serbia d Blood Transfusion Institute of Serbia, Belgrade, Serbia b
a r t i c l e
i n f o
Article history: Received 27 September 2014 Accepted 19 March 2015 Available online xxx Keywords: Blood donors Hepatitis C Prevalence Risk factors
a b s t r a c t Background: The epidemiological characteristics of hepatitis C virus (HCV) infection has not yet been described in Serbia. Aims: To determine the prevalence of anti-HCV-positive individuals among first-time blood donors and the risk factors for hepatitis C transmission. Methods: A multicentre case–control study nested within a prospective cohort study was conducted at 10 main transfusion centres in Serbia in 2013 and 27,160 blood donors who gave blood for the first time were included. Blood donors with confirmed anti-HCV positivity and seronegative controls were enrolled to determine the risk factors. Results: Of 27,160 blood donors 52 were anti-HCV-positive; seroprevalence was 0.19%. By univariate analysis, marital status, educational level, drug use, previous transfusion, tattooing, non-use of condoms and number of sexual partners, were risk factors for hepatitis C. In the final multivariate analysis, three factors remained independently predictive: drug use, tattooing and previous blood transfusion. In total, 87.5% of cases had at least one of the risk factors for HCV transmission; 20.9% presumed that they knew when the infection occurred. Conclusion: HCV seroprevalence in Serbia is higher than in developed European countries. Preventive measures need to be directed towards drug use and tattooing facilities. The admission questionnaire for blood donors should be improved. © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
1. Introduction Hepatitis C virus (HCV) infection is a serious global health problem. It is estimated that 3% of the world population is infected with this virus, or there are approximately 150 million infected people worldwide [1]. It is also estimated that HCV is the cause of 25% to over 50% of all chronic hepatitis cases; it is one of the main causes of hepatocellular carcinoma, and the most common cause of liver transplant [2,3]. Because of its importance several monitoring systems of epidemiological data on HCV infection have been organised in Europe – such as that organised by the European Centre for Disease Prevention and Control (ECDC). Unfortunately, Serbia is not
∗ Corresponding author at: Clinic for Infectious and Tropical Disease, Bulevar Oslobodjenja 16, 11000 Belgrade, Serbia. Tel.: +381 64 164 53 32; fax: +381 11 2684 272. E-mail address: [email protected] (N. Mitrovic).
included in these monitoring systems because of a lack of adequate data. The data available are mostly based on the results of retrospective studies, which included patients with chronic hepatitis C infection who were in a treatment programme or they relate to specific population groups (intravenous drug users, prisoners, patients on haemodialysis, etc.) [4,5]. There are not enough epidemiological data on the spread of HCV infection in Serbia or modes of virus transmission. After the discovery of HCV it became clear that it is the major cause of post-transfusion non-A, non-B hepatitis. Since then, all the blood collected by voluntary blood donation has been routinely tested for this virus. Today, the risk of transmission of HCV through blood transfusion in developed countries is extremely low, at one in a couple of million blood units, owing to the use of highly sensitive diagnostic techniques based on the detection of HCV RNA, such as molecular testing for HCV RNA utilising nucleic acid amplification technology (NAT). In Africa, Asia and Latin America the risk remains much higher, even as high as 1:65,000 in Egypt [6].
http://dx.doi.org/10.1016/j.dld.2015.03.019 1590-8658/© 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Mitrovic N, et al. Seroprevalence and risk factors for hepatitis C virus infection among blood donors in Serbia: A multicentre study. Dig Liver Dis (2015), http://dx.doi.org/10.1016/j.dld.2015.03.019
G Model YDLD-2857; No. of Pages 5
ARTICLE IN PRESS
2
N. Mitrovic et al. / Digestive and Liver Disease xxx (2015) xxx–xxx
The systematic testing for HCV of all blood collected from blood donors throughout the entire Republic of Serbia began in January 1994. To date, no research has been conducted in Serbia on the epidemiology of HCV infection among voluntary blood donors. Determining the prevalence and potential risk factors for HCV infection among them is important for providing the missing epidemiological data on voluntary blood donors who originate from select mostly healthy individuals, and the prevalence of anti-HCV positivity among them is expected to be the lowest in the Serbian population. Furthermore, these data allow a comparison to be made with other countries in which such studies have been conducted [7–11]. Determining the prevalence of anti-HCV-positive individuals while obtaining an insight into the risk factors can be used to improve blood transfusion safety. The aim of our study was to determine the prevalence of antiHCV-positive individuals among first-time blood donors and to determine the risk factors for HCV infection. 2. Methods 2.1. Study design This multicentre case–control study nested within a prospective cohort study was conducted between January 1st and December 31st 2013 at 10 transfusion centres in Serbia: Belgrade, Novi Sad, Nis, Subotica, Sombor, Pancevo, Kraljevo, Cacak, Loznica and Negotin. To estimate the prevalence of HCV seropositivity among blood donors, a cohort of 27,160 voluntary blood donors who gave blood for the first time were enrolled in the study. In Serbia voluntary blood donation is conducted in accordance with standards set by the Ministry of Health and the Law on Blood Transfusion. Based on these standards every potential blood donor is subjected to a medical examination; blood is typed according to the ABO and Rh systems and checked for haemoglobin level. Every single blood donor completes a donor’s admission questionnaire, which includes questions on basic demographic data, data on medical conditions and the data on high-risk behaviour. This questionnaire ensures that the blood is not taken from persons with malignant and chronic non-infectious diseases. Also, blood is not taken from hepatitis B virus (HBV)-, human immunodeficiency virus (HIV)- or HCV-positive subjects. Current intravenous drug abuse, chronic alcoholism and high-risk sexual behaviour were contraindications for blood donation. In the case of previous drug abuse, the examiner individually assesses the risk of blood donation. Any unsuitable donors are rejected, temporarily or permanently. Every single unit of blood is tested for transmissible diseases: HIV infection, hepatitis B, hepatitis C and syphilis. A thirdgeneration HCV ELISA test, which detects anti-HCV antibodies, is used to test the blood. If the initial test is positive, then one more test is performed – the ELISA confirmation test. If anti-HCV positivity is confirmed, the blood donors are invited by mail to a consultation, where they are told of the positivity, and are then referred to the proper medical facility for further diagnostics and treatment. 2.2. Selection of cases and controls The cases were voluntary blood donors with confirmed antiHCV positivity; infections by other inoculation viruses (HIV or HBV) were excluded. Individuals who voluntarily accepted to be part of the study were given an anonymous questionnaire compiled for this study. The participants completed this questionnaire by themselves in private. The questionnaire consists of two parts. The first part is devoted to general demographic data. The second part of the questionnaire explores all the risk factors confirmed or
discussed previously in the literature (questionnaire available on request from the authors). The participants placed the completed questionnaire in an empty envelope and sealed it; these were then labelled with ordinal numbers in the sequence of those included in the study. A separate register was kept of which envelope number corresponded to which donor. Donors’ personal data are kept by the transfusion centres; owing to requirements set by the Ethics Committee these was not available to us and are accessible only by special permission. Envelopes were opened for the first time during data analysis. For each case patient two sex-matched and age-matched (within 5 years of the case patients’ ages) controls were selected from the same population of inclusion as the case patients. Controls were voluntary blood donors from the same transfusion centre as the case patients, without HCV infection or other parenterally acquired diseases, who voluntarily gave blood in the same week when the case patient was included in the study. The controls completed the same questionnaire in the exact same manner as the case patients when they received the test results and picked up their blood donor’s booklets. In 52 individuals anti-HCV positivity was confirmed, of whom 32 were included in the case–control study for the purpose of identifying the risk factors (response rate 61.5%). Of the remaining 20 individuals who did not take part in the case–control study, 16 (30.8%) were not contacted or were unavailable, regardless of numerous attempts made to contact them by post or telephone. Four (7.7%) refused to take part in the study without providing any reasons for their decision. Among the controls, none of those invited to take part in the study refused. Therefore, 32 cases and 64 controls were included in the case–control study. This study was approved by the Ethics Committee of the Transfusion Institute of Serbia (No. 8280/3) and by the Ethics Committee of the Belgrade School of Medicine (No. 29/IX-7). All participants in the study provided written informed consent.
2.3. Statistical analysis The univariate matched odds ratio and their 95% confidence intervals (CI) were determined for each manner of HCV transmission. The Chi-squared test and the Mann–Whitney U test were used for the purpose of determining the statistical significance of certain risk factors. The risk factors for which the univariate analysis gave p < 0.1 were included in multivariate analyses using conditional multiple logistic regression. The value p < 0.05 was considered to indicate statistical significance.
3. Results In the time frame of one year (January–December 2013) 27,160 first-time voluntary blood donors came to the transfusion centres and were also tested for anti-HCV positivity. They included 52 with confirmed anti-HCV positivity by initial and confirmation tests. The seroprevalence was 0.19% (95% CI: 0.14–0.24%). In the case–control study of all 52 eligible anti-HCV-positive donors, 32 (61.5%) were enrolled in the study. For the 32 cases, 64 matched controls were included. The baseline characteristics of the cases and controls are presented in Table 1. Most of the case patients were men, with a gender ratio of 3.8:1. The average age was 32.1 ± 8.4 years (18–60 years). Most participants (78.1%) were aged 25–44 years and only three participants (9.4%) were over the age of 45 years. The difference between groups was marginally statistically significant (p = 0.073) with regard to education. When we compared elementary/secondary education level with high school/faculty, we found that the controls had a
Please cite this article in press as: Mitrovic N, et al. Seroprevalence and risk factors for hepatitis C virus infection among blood donors in Serbia: A multicentre study. Dig Liver Dis (2015), http://dx.doi.org/10.1016/j.dld.2015.03.019
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N. Mitrovic et al. / Digestive and Liver Disease xxx (2015) xxx–xxx Table 1 The baseline characteristics of the participating case patients and controls. Variables
Cases (n = 32)
Controls (n = 64)
p value
Male gender Age groups (years) 18–24 25–34 35–44 45–54 55–65 Education Elementary school (8 years of education) Secondary school (12 years of education) High school (15 years of education) University (>15 years) Marital status Not married
25 (78.1%)
50 (78.1%)
1.00
4 (12.5%) 16 (50%) 9 (28.1%) 2 (6.3%) 1 (3.1%)
8 (12.5%) 32 (50%) 18 (28.1%) 4 (6.3%) 2 (3.1%)
1.00
3 (9.4%)
5 (7.8%)
22 (68.8%)
30 (46.9%)
6 (18.8%)
15 (23.4%)
1 (3.1%)
14 (21.9%)
24 (75%)
33 (51.6%)
3
Table 3 Final multivariable logistic regression model of significant risk factors associated with anti-hepatitis C virus positivity. Mutivariate analysisa
Risk factors
OR Married status Education levelb Drug use Transfusion Tatooing Use of condoms Anal sex Previous imprisonment
0.073
1.75 1.44 16.5 11.24 8.83 2.84 2.29 3.82
95% CI
p
0.38–8.11 0.318–6.55 2.54–107.2 1.81–69.7 2.02–38.53 0.54–14.96 0.21–24.7 0.34–43.1
0.472 0.634 0.003 0.009 0.004 0.218 0.494 0.278
OR, odds ratio; CI, confidence interval. a The results from a conditional logistic regression model on age and sex matched data. b Elementary/secondary school compared to high school/faculty.
0.028
significantly higher educational level; 45.3% high school or university graduates compared with 21.9% of the cases (p = 0.025). Concerning marital status, 25% of cases and 48.4% of controls were married and this difference was statistically significant (p = 0.028). Concerning drug use, 15 case patients (46.9%) and only 3 (4.7%) of the controls reported that they had previously used drugs (p < 0.001; OR = 17.9; 95% CI 4.6–69.2). Of the total number of case patients who used drugs, 8 (25%) of them used both intranasal and intravenous drugs, while the rest of them, 7 (21.9%), only reported intranasal use. None of the participants said that they were actively taking drugs when they donated blood. Receiving a blood transfusion was also associated with HCV infection (p = 0.009; OR 5.0; 95% CI 1.4–18.2). When the year in which the transfusion was received was taken in account, there was a noticeable difference between case patients and controls; it is most prominent in the groups that received a transfusion before 1994; 12.5% of case patients and 1.6% of controls received transfusions before 1994. Tattooing was associated with anti-HCV positivity (p < 0.001; OR = 16.1; 95% CI 5.3–48.6), while the number of tattoos was not.
Only one case patient had any piercings but none of the controls had any. Engaging in sexual intercourse was not associated with antiHCV positivity (p = 0.37). Case patients statistically more frequently had sex without condoms than controls (83.9% and 61% respectively; p = 0.026). Also, the case patients had statistically much higher numbers of sexual partners than the controls (the average number of sexual partners was 9.5 vs. 3.5 respectively; p = 0.014). Engaging in anal sex and sexual relations with persons at risk of HCV (drug addicts, promiscuous individuals) were not statistically significant. Only one case patient knowingly had sexual intercourse with a person with chronic hepatitis C. There was no statistical significance for surgical procedures, extensive dental procedures accompanied by haemorrhage, previous imprisonment or abortions. Regarding other risk factors, two participants said that they had been exposed to blood in the workplace or that they may have lived with a person with HCV infection. One participant had a sexually transmitted disease (STD). None of the participants had acupuncture, circumcision or accidental puncture with a used medical needle and no maternal HCV infection or drug use was reported. The risk factors for HCV infection are presented in Table 2. Individual independent risk factors with p < 0.1 in the univariate analysis were included in the final multivariate logistic regression. In the multivariate analysis exposures that remained significantly associated with HCV infection were: drug use (OR = 16.5; CI = 2.54–107.2), transfusions (OR = 11.2; CI = 1.81–69.7) and tattooing (OR = 8.8; CI = 2.02–38.5; Table 3).
Table 2 Univariate analysis of putative risk factors for hepatitis C virus infection. Variable
Cases (n = 32), n (%)
Controls (n = 64), n (%)
mOR
Drug use I.V. drug use Nasal drug use Transfusiona Surgery Invasive dental treatment Tatooing Previous imprisonment Education – high school/university Sexual activity Inconsistent condom use High-risk sexual partnerb Anal sex Abortions
15 (46.9%) 8 (25%) 12 (37.5%) 8 (25%) 14 (43.8%) 4 (12.5%) 20 (62.5%) 4 (12.5%) 7 (21.9%) 31 (96.9%) 26 (83.9%) 6 (19.4%) 5 (16.1%) 1 (14.3%)
3 (4.7%) 1 (1.6%) 2 (3.1%) 4 (6.3%) 16 (25%) 6 (9.4%) 6 (9.4%) 2 (3.1%) 29 (45.3%) 59 (92.2%) 36 (61.0%) 5 (8.5%) 3 (5.1%) 3 (21.4%)
17.94 21.0 18.6 5.0 2.33 1.381 16.11 4.43 2.9 2.63 3.32 2.59 3.59 0.61
95% CI 4.65–69.28 2.49–176.95 3.83–90.26 1.38–18.17 0.95–5.732 0.36–5.291 5.34–48.59 0.766–25.614 1.12–7.82 0.29–23.49 1.12–9.89 0.72–9.30 0.79–16.17 0.05–7.24
p
ARTICLE IN PRESS Digestive and Liver Disease xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld
Liver, Pancreas and Biliary Tract
Seroprevalence and risk factors for hepatitis C virus infection among blood donors in Serbia: A multicentre study Nikola Mitrovic a,∗ , Dragan Delic a,b , Ljiljana Markovic-Denic b,c , Milica Jovicic d , Natasa Popovic a , Ksenija Bojovic a,b , Jasmina Simonovic Babic a,b , Neda Svirtlih a,b a
Clinic for Infectious and Tropical Disease, Belgrade, Serbia University of Belgrade, Faculty of Medicine, Belgrade, Serbia c Institute of Epidemiology, Belgrade, Serbia d Blood Transfusion Institute of Serbia, Belgrade, Serbia b
a r t i c l e
i n f o
Article history: Received 27 September 2014 Accepted 19 March 2015 Available online xxx Keywords: Blood donors Hepatitis C Prevalence Risk factors
a b s t r a c t Background: The epidemiological characteristics of hepatitis C virus (HCV) infection has not yet been described in Serbia. Aims: To determine the prevalence of anti-HCV-positive individuals among first-time blood donors and the risk factors for hepatitis C transmission. Methods: A multicentre case–control study nested within a prospective cohort study was conducted at 10 main transfusion centres in Serbia in 2013 and 27,160 blood donors who gave blood for the first time were included. Blood donors with confirmed anti-HCV positivity and seronegative controls were enrolled to determine the risk factors. Results: Of 27,160 blood donors 52 were anti-HCV-positive; seroprevalence was 0.19%. By univariate analysis, marital status, educational level, drug use, previous transfusion, tattooing, non-use of condoms and number of sexual partners, were risk factors for hepatitis C. In the final multivariate analysis, three factors remained independently predictive: drug use, tattooing and previous blood transfusion. In total, 87.5% of cases had at least one of the risk factors for HCV transmission; 20.9% presumed that they knew when the infection occurred. Conclusion: HCV seroprevalence in Serbia is higher than in developed European countries. Preventive measures need to be directed towards drug use and tattooing facilities. The admission questionnaire for blood donors should be improved. © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
1. Introduction Hepatitis C virus (HCV) infection is a serious global health problem. It is estimated that 3% of the world population is infected with this virus, or there are approximately 150 million infected people worldwide [1]. It is also estimated that HCV is the cause of 25% to over 50% of all chronic hepatitis cases; it is one of the main causes of hepatocellular carcinoma, and the most common cause of liver transplant [2,3]. Because of its importance several monitoring systems of epidemiological data on HCV infection have been organised in Europe – such as that organised by the European Centre for Disease Prevention and Control (ECDC). Unfortunately, Serbia is not
∗ Corresponding author at: Clinic for Infectious and Tropical Disease, Bulevar Oslobodjenja 16, 11000 Belgrade, Serbia. Tel.: +381 64 164 53 32; fax: +381 11 2684 272. E-mail address: [email protected] (N. Mitrovic).
included in these monitoring systems because of a lack of adequate data. The data available are mostly based on the results of retrospective studies, which included patients with chronic hepatitis C infection who were in a treatment programme or they relate to specific population groups (intravenous drug users, prisoners, patients on haemodialysis, etc.) [4,5]. There are not enough epidemiological data on the spread of HCV infection in Serbia or modes of virus transmission. After the discovery of HCV it became clear that it is the major cause of post-transfusion non-A, non-B hepatitis. Since then, all the blood collected by voluntary blood donation has been routinely tested for this virus. Today, the risk of transmission of HCV through blood transfusion in developed countries is extremely low, at one in a couple of million blood units, owing to the use of highly sensitive diagnostic techniques based on the detection of HCV RNA, such as molecular testing for HCV RNA utilising nucleic acid amplification technology (NAT). In Africa, Asia and Latin America the risk remains much higher, even as high as 1:65,000 in Egypt [6].
http://dx.doi.org/10.1016/j.dld.2015.03.019 1590-8658/© 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Mitrovic N, et al. Seroprevalence and risk factors for hepatitis C virus infection among blood donors in Serbia: A multicentre study. Dig Liver Dis (2015), http://dx.doi.org/10.1016/j.dld.2015.03.019
G Model YDLD-2857; No. of Pages 5
ARTICLE IN PRESS
2
N. Mitrovic et al. / Digestive and Liver Disease xxx (2015) xxx–xxx
The systematic testing for HCV of all blood collected from blood donors throughout the entire Republic of Serbia began in January 1994. To date, no research has been conducted in Serbia on the epidemiology of HCV infection among voluntary blood donors. Determining the prevalence and potential risk factors for HCV infection among them is important for providing the missing epidemiological data on voluntary blood donors who originate from select mostly healthy individuals, and the prevalence of anti-HCV positivity among them is expected to be the lowest in the Serbian population. Furthermore, these data allow a comparison to be made with other countries in which such studies have been conducted [7–11]. Determining the prevalence of anti-HCV-positive individuals while obtaining an insight into the risk factors can be used to improve blood transfusion safety. The aim of our study was to determine the prevalence of antiHCV-positive individuals among first-time blood donors and to determine the risk factors for HCV infection. 2. Methods 2.1. Study design This multicentre case–control study nested within a prospective cohort study was conducted between January 1st and December 31st 2013 at 10 transfusion centres in Serbia: Belgrade, Novi Sad, Nis, Subotica, Sombor, Pancevo, Kraljevo, Cacak, Loznica and Negotin. To estimate the prevalence of HCV seropositivity among blood donors, a cohort of 27,160 voluntary blood donors who gave blood for the first time were enrolled in the study. In Serbia voluntary blood donation is conducted in accordance with standards set by the Ministry of Health and the Law on Blood Transfusion. Based on these standards every potential blood donor is subjected to a medical examination; blood is typed according to the ABO and Rh systems and checked for haemoglobin level. Every single blood donor completes a donor’s admission questionnaire, which includes questions on basic demographic data, data on medical conditions and the data on high-risk behaviour. This questionnaire ensures that the blood is not taken from persons with malignant and chronic non-infectious diseases. Also, blood is not taken from hepatitis B virus (HBV)-, human immunodeficiency virus (HIV)- or HCV-positive subjects. Current intravenous drug abuse, chronic alcoholism and high-risk sexual behaviour were contraindications for blood donation. In the case of previous drug abuse, the examiner individually assesses the risk of blood donation. Any unsuitable donors are rejected, temporarily or permanently. Every single unit of blood is tested for transmissible diseases: HIV infection, hepatitis B, hepatitis C and syphilis. A thirdgeneration HCV ELISA test, which detects anti-HCV antibodies, is used to test the blood. If the initial test is positive, then one more test is performed – the ELISA confirmation test. If anti-HCV positivity is confirmed, the blood donors are invited by mail to a consultation, where they are told of the positivity, and are then referred to the proper medical facility for further diagnostics and treatment. 2.2. Selection of cases and controls The cases were voluntary blood donors with confirmed antiHCV positivity; infections by other inoculation viruses (HIV or HBV) were excluded. Individuals who voluntarily accepted to be part of the study were given an anonymous questionnaire compiled for this study. The participants completed this questionnaire by themselves in private. The questionnaire consists of two parts. The first part is devoted to general demographic data. The second part of the questionnaire explores all the risk factors confirmed or
discussed previously in the literature (questionnaire available on request from the authors). The participants placed the completed questionnaire in an empty envelope and sealed it; these were then labelled with ordinal numbers in the sequence of those included in the study. A separate register was kept of which envelope number corresponded to which donor. Donors’ personal data are kept by the transfusion centres; owing to requirements set by the Ethics Committee these was not available to us and are accessible only by special permission. Envelopes were opened for the first time during data analysis. For each case patient two sex-matched and age-matched (within 5 years of the case patients’ ages) controls were selected from the same population of inclusion as the case patients. Controls were voluntary blood donors from the same transfusion centre as the case patients, without HCV infection or other parenterally acquired diseases, who voluntarily gave blood in the same week when the case patient was included in the study. The controls completed the same questionnaire in the exact same manner as the case patients when they received the test results and picked up their blood donor’s booklets. In 52 individuals anti-HCV positivity was confirmed, of whom 32 were included in the case–control study for the purpose of identifying the risk factors (response rate 61.5%). Of the remaining 20 individuals who did not take part in the case–control study, 16 (30.8%) were not contacted or were unavailable, regardless of numerous attempts made to contact them by post or telephone. Four (7.7%) refused to take part in the study without providing any reasons for their decision. Among the controls, none of those invited to take part in the study refused. Therefore, 32 cases and 64 controls were included in the case–control study. This study was approved by the Ethics Committee of the Transfusion Institute of Serbia (No. 8280/3) and by the Ethics Committee of the Belgrade School of Medicine (No. 29/IX-7). All participants in the study provided written informed consent.
2.3. Statistical analysis The univariate matched odds ratio and their 95% confidence intervals (CI) were determined for each manner of HCV transmission. The Chi-squared test and the Mann–Whitney U test were used for the purpose of determining the statistical significance of certain risk factors. The risk factors for which the univariate analysis gave p < 0.1 were included in multivariate analyses using conditional multiple logistic regression. The value p < 0.05 was considered to indicate statistical significance.
3. Results In the time frame of one year (January–December 2013) 27,160 first-time voluntary blood donors came to the transfusion centres and were also tested for anti-HCV positivity. They included 52 with confirmed anti-HCV positivity by initial and confirmation tests. The seroprevalence was 0.19% (95% CI: 0.14–0.24%). In the case–control study of all 52 eligible anti-HCV-positive donors, 32 (61.5%) were enrolled in the study. For the 32 cases, 64 matched controls were included. The baseline characteristics of the cases and controls are presented in Table 1. Most of the case patients were men, with a gender ratio of 3.8:1. The average age was 32.1 ± 8.4 years (18–60 years). Most participants (78.1%) were aged 25–44 years and only three participants (9.4%) were over the age of 45 years. The difference between groups was marginally statistically significant (p = 0.073) with regard to education. When we compared elementary/secondary education level with high school/faculty, we found that the controls had a
Please cite this article in press as: Mitrovic N, et al. Seroprevalence and risk factors for hepatitis C virus infection among blood donors in Serbia: A multicentre study. Dig Liver Dis (2015), http://dx.doi.org/10.1016/j.dld.2015.03.019
G Model
ARTICLE IN PRESS
YDLD-2857; No. of Pages 5
N. Mitrovic et al. / Digestive and Liver Disease xxx (2015) xxx–xxx Table 1 The baseline characteristics of the participating case patients and controls. Variables
Cases (n = 32)
Controls (n = 64)
p value
Male gender Age groups (years) 18–24 25–34 35–44 45–54 55–65 Education Elementary school (8 years of education) Secondary school (12 years of education) High school (15 years of education) University (>15 years) Marital status Not married
25 (78.1%)
50 (78.1%)
1.00
4 (12.5%) 16 (50%) 9 (28.1%) 2 (6.3%) 1 (3.1%)
8 (12.5%) 32 (50%) 18 (28.1%) 4 (6.3%) 2 (3.1%)
1.00
3 (9.4%)
5 (7.8%)
22 (68.8%)
30 (46.9%)
6 (18.8%)
15 (23.4%)
1 (3.1%)
14 (21.9%)
24 (75%)
33 (51.6%)
3
Table 3 Final multivariable logistic regression model of significant risk factors associated with anti-hepatitis C virus positivity. Mutivariate analysisa
Risk factors
OR Married status Education levelb Drug use Transfusion Tatooing Use of condoms Anal sex Previous imprisonment
0.073
1.75 1.44 16.5 11.24 8.83 2.84 2.29 3.82
95% CI
p
0.38–8.11 0.318–6.55 2.54–107.2 1.81–69.7 2.02–38.53 0.54–14.96 0.21–24.7 0.34–43.1
0.472 0.634 0.003 0.009 0.004 0.218 0.494 0.278
OR, odds ratio; CI, confidence interval. a The results from a conditional logistic regression model on age and sex matched data. b Elementary/secondary school compared to high school/faculty.
0.028
significantly higher educational level; 45.3% high school or university graduates compared with 21.9% of the cases (p = 0.025). Concerning marital status, 25% of cases and 48.4% of controls were married and this difference was statistically significant (p = 0.028). Concerning drug use, 15 case patients (46.9%) and only 3 (4.7%) of the controls reported that they had previously used drugs (p < 0.001; OR = 17.9; 95% CI 4.6–69.2). Of the total number of case patients who used drugs, 8 (25%) of them used both intranasal and intravenous drugs, while the rest of them, 7 (21.9%), only reported intranasal use. None of the participants said that they were actively taking drugs when they donated blood. Receiving a blood transfusion was also associated with HCV infection (p = 0.009; OR 5.0; 95% CI 1.4–18.2). When the year in which the transfusion was received was taken in account, there was a noticeable difference between case patients and controls; it is most prominent in the groups that received a transfusion before 1994; 12.5% of case patients and 1.6% of controls received transfusions before 1994. Tattooing was associated with anti-HCV positivity (p < 0.001; OR = 16.1; 95% CI 5.3–48.6), while the number of tattoos was not.
Only one case patient had any piercings but none of the controls had any. Engaging in sexual intercourse was not associated with antiHCV positivity (p = 0.37). Case patients statistically more frequently had sex without condoms than controls (83.9% and 61% respectively; p = 0.026). Also, the case patients had statistically much higher numbers of sexual partners than the controls (the average number of sexual partners was 9.5 vs. 3.5 respectively; p = 0.014). Engaging in anal sex and sexual relations with persons at risk of HCV (drug addicts, promiscuous individuals) were not statistically significant. Only one case patient knowingly had sexual intercourse with a person with chronic hepatitis C. There was no statistical significance for surgical procedures, extensive dental procedures accompanied by haemorrhage, previous imprisonment or abortions. Regarding other risk factors, two participants said that they had been exposed to blood in the workplace or that they may have lived with a person with HCV infection. One participant had a sexually transmitted disease (STD). None of the participants had acupuncture, circumcision or accidental puncture with a used medical needle and no maternal HCV infection or drug use was reported. The risk factors for HCV infection are presented in Table 2. Individual independent risk factors with p < 0.1 in the univariate analysis were included in the final multivariate logistic regression. In the multivariate analysis exposures that remained significantly associated with HCV infection were: drug use (OR = 16.5; CI = 2.54–107.2), transfusions (OR = 11.2; CI = 1.81–69.7) and tattooing (OR = 8.8; CI = 2.02–38.5; Table 3).
Table 2 Univariate analysis of putative risk factors for hepatitis C virus infection. Variable
Cases (n = 32), n (%)
Controls (n = 64), n (%)
mOR
Drug use I.V. drug use Nasal drug use Transfusiona Surgery Invasive dental treatment Tatooing Previous imprisonment Education – high school/university Sexual activity Inconsistent condom use High-risk sexual partnerb Anal sex Abortions
15 (46.9%) 8 (25%) 12 (37.5%) 8 (25%) 14 (43.8%) 4 (12.5%) 20 (62.5%) 4 (12.5%) 7 (21.9%) 31 (96.9%) 26 (83.9%) 6 (19.4%) 5 (16.1%) 1 (14.3%)
3 (4.7%) 1 (1.6%) 2 (3.1%) 4 (6.3%) 16 (25%) 6 (9.4%) 6 (9.4%) 2 (3.1%) 29 (45.3%) 59 (92.2%) 36 (61.0%) 5 (8.5%) 3 (5.1%) 3 (21.4%)
17.94 21.0 18.6 5.0 2.33 1.381 16.11 4.43 2.9 2.63 3.32 2.59 3.59 0.61
95% CI 4.65–69.28 2.49–176.95 3.83–90.26 1.38–18.17 0.95–5.732 0.36–5.291 5.34–48.59 0.766–25.614 1.12–7.82 0.29–23.49 1.12–9.89 0.72–9.30 0.79–16.17 0.05–7.24
p
