Risk factors for hepatitis C virus infection among blood donors in southern Brazil: a case-control study

The worldwide prevalence of hepatitis C virus infection is estimated by the World Health Organization (WHO) to be approximately 3% – corresponding to 170 million infected persons [1, 2]. In Brazil, WHO estimates suggest that between 2.5 and 4.9% of the general population present anti-HCV antibodies [3]. This corresponds to as many as 3.9 to 7.6 million chronic carriers at risk for developing liver cirrhosis and/or liver cancer. Studies show that among Brazilian patients with chronic liver disease, 20 to 58% are anti-HCV positive [4], and that in southern Brazil 27% of the patients with hepatocellular carcinoma are anti-HCV positive [5].

While the search for an effective therapy [6] and vaccine [7] continues, prevention and control of HCV infection should be the goals of public health efforts. Preventive strategies aim to reduce the exposure to HCV should be based on blood testing of individuals, screening of blood and blood products, sterilization of reusable equipment, destruction of potentially contaminated disposable instruments, and promotion of barrier methods of contraception to prevent sexually transmitted diseases [2]. To increase the efficacy of these interventions, it is important that the main risk factors for HCV infection in different populations be known. Therefore, the present case-control study was designed to evaluate risk factors in a representative sample of blood donors in southern Brazil.

This case-control study shows that first-time blood donors, as well as 30 to 59 year-old donors and less educated donors were at higher risk for HCV seropositivity. In addition, our results confirm that injection drug use, blood transfusion, incarceration, tattooing, history of sexually transmitted diseases, and sexual intercourse with injection drug users, partners with hepatitis, or carriers of HBV or HCV increase the risk for a positive anti-HCV test. In the study of risk factors associated with the presence of HCV antibodies, the potential for bias must be ruled out. In the present study, the sampling process enabled a representative sample of donors in the city of Porto Alegre to be detected and enrolled. The inclusion of center-matched control donors with a negative HCV test avoided bias related to differences in the recruitment policy and in the anti-HCV test employed in each center. Immunoblot tests and polymerase chain reaction (PCR) or transcription-mediated amplification (TMA) were not adopted as a routine to test blood donors in Brazil. Even though the specificity of currently available EIAs for anti-HCV is high, the positive predictive value is lower in blood donors [9]. Accordingly, we avoided to label the cases as HCV infected, but anti-HCV seropositives.

An attempt was made to minimize recall bias by asking cases and controls to report information about the same period, and by using the same standardized questionnaire. Since most episodes of hepatitis C are free of symptoms, cases were as likely as controls to recall exposures potentially associated with HCV infection.

When interpreting the results of this study, it is meaningful to bear in mind that the eligible donors were in good health and did not represent the general population.

First-time blood donors had twice the risk for presenting a positive HCV test. This association is plausible, since first-time donors have never been screened [10, 11]. The test-seeking behavior for infectious diseases is unlikely as the Brazilian public health care system offers alternative test sites. In addition, first-time blood donors are less likely to report exposure to risk factors for HCV infection. For instance, in the United States, the deferrable risk (defined as estimated prevalence rate for risk behaviors that would have been a basis for donation deferral if reported at the time of the donor screening among first-time donors was 1.6 times greater than among repeated donors [12]. In this study, 26% of all donors presented a history of jaundice, incarceration, injection drug use, and tattooing. These donors should have been excluded in the predonation interview, according to the Brazilian criteria for blood donation [13].

Concerning demographic variables, the increase in the risk for HCV seropositivity between 30 and 59 years was different to that described for donors in Australia [14] or the United States [15, 16], where the infection rate declines in persons greater than 50 years old, and similar that described in other region of our country [17]. This pattern of transmission suggests that the risk for HCV infection was greater in the distant past [18] and reached a decreased risk of infection along generations as consequence of improving sanitary and socioeconomic conditions over time.

Our results show an inverse and statistically significant association between positive HCV testing and schooling – the risk was greater among illiterate donors or donors with little schooling. These socioeconomic factors have been previously described as acting through risk factors such as illicit drug use [15] or unsafe injection practices [19].

In terms of environmental exposure, having been incarcerated in a juvenile detention center or prison was the main risk factor, independently associated with a five-fold increase in positive HCV testing. The association between a previous imprisonment and positive HCV testing is a proxy of the true risks. The risk for inmates to be HCV positive has been associated with injection drug use, tattooing and previous incarceration [20–26]. In addition, the possibility of person-to-person HCV transmission through exposure to contaminated blood cannot be dismissed [27].

Our study shows that exposure to blood was, and still is, the main risk factor for HCV infection. Blood transfusion more than 10 years ago was associated with positive HCV testing, and the association became even stronger after adjustment for confounding factors. The residual risk for transfusion-transmitted hepatitis C infection decreased after Brazilian blood centers adopted anti-HCV screening tests 10 years ago, but it is still higher than in developed countries [28]. As in other studies [10, 11, 17, 29–33], we observed that illegal injection drug use is the dominant mode of HCV transmission, mostly due to sharing of needles or syringes [34]. Approximately 75% of Brazilian injection drug users are HCV seropositive [35], and 85% of them share needles [36]. In addition, other parenteral exposure, such as tattooing, was independently associated with HCV seropositivity. Tattooing still is not a regulated businesses and, in the past, most of the tattoing occurred at places where contamination were more likely. This potential risk for HCV transmission in blood donors has been previously reported [11, 30]; presumably, non-sterile or non-disposable equipment is the source of transmission [37]. HCV seropositivity was also independently associated with personal history of jaundice; however, jaundice may be a marker of disease, rather than a risk factor. In this study, the prevalence of HCV infection was not associated with employment in a health-related occupation. Although occupational exposure can result in infection, [38, 39] only 8.9% of blood donors were health care workers and 32% did not handle blood samples.

The importance of sexual activity in the transmission of HCV has not been well-established [37]. Nevertheless, studies with blood donors suggest an association between sexual transmission and HCV [10, 11, 17, 31, 40]. This study detected an independent association between sexual behavior and positive anti-HCV test. The results of the logistic regression model show that the number of sexually transmitted diseases during life and sexual intercourse with injection drug users and with HBV or HCV carriers were independent risk factors for anti-HCV positivity. Even though number of sexual partners and sexual orientation were associated in the bivariate analysis, they were not independent of other risk factors such as transfusion and injection drug use by the donor or his/her sexual partner. In South America, the prevalence of HCV infection in heterosexuals attending STD clinics and with no history of injection drug abuse (11.5%) is greater than in North America (6.0%) and Europe (1.9%) [37]. It is speculated that HCV transmission may be facilitated by sexually transmitted diseases [41, 42]. However, there is a possibility that HCV seropositivity associated with sexual intercourse with injection drug users or HBV/ HCV carriers may result from actual sexual transmission of HCV – although it may also result from exposure to unreported parenteral risk factors or from sharing certain personal items, such as toothbrushes or razors, which can result in accidental exposure to the partner's blood [11, 33, 42].

In conclusion, this case-control study confirmed some independent risk factors for anti-HCV positive test described in other studies of blood donors. The hierarchical multivariate analysis identified age, schooling, incarceration, past transfusion, tattooing, intravenous drug use, number of sexually transmitted diseases, sexual intercourse with injection drug users and partners with hepatitis B or C as the main risk factors for HCV seropositivity in the present population of southern Brazilian donors. Some characteristics of sexual behavior were detected as independent risk factors, suggesting that sexual intercourse is an important source of transmission. The identification of groups at risk and the planning of interventions aimed at controlling HCV infection should take these findings into account.