Behavioral and Healthcare-Associated Risk Factors for Chronic Hepatitis C Virus Infection in Korea

Hepatitis C virus (HCV) infection is one of the most common causes of chronic liver disease worldwide, affecting about 170 million people (1). HCV-infected patients are at risk for chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), and they serve as a reservoir for HCV transmission. As there is no effective vaccine for HCV infection, finding risk factors and modes of HCV transmission has been the focus of elaborating the preventive strategies.

Significant geographic and temporal differences have been observed in the global epidemiology of HCV infection (2, 3). A lot of studies have reported on the risk factors of HCV infection in Western countries (1, 4, 5); however, studies in Asian countries, including Korea, are limited (6-8). Even in Asian countries, some differences in the risk factors related to HCV transmission have been observed. For example, traditional procedures such as acupuncture or other folk remedies are considered significant risk factors in Japan and Taiwan (9), while eyebrow tattooing for cosmetic purposes is an important risk factor for HCV infection in Vietnam and Cambodia (9).

In Korea, hepatitis B virus (HBV) infection has been a major cause of liver cirrhosis and hepatocellular carcinoma (10). However, the prevalence of HBV has gradually decreased along with successful universal immunization program (11, 12). Although the relative importance of HCV infection as a cause of liver disease has been increasing in Korea, studies on the risk factors related to HCV infection are very limited during the recent 10 yr. Although transfusion before 1992 was a strong factor for HCV transmission (13, 14), studies of HCV epidemiology with regard to other risk factors, such as injection drug use, needle stick injury, surgery, and tattooing have been limited in Korea (15-17).

The present study aimed to assess the risk factors for HCV infection in Korea by investigating the frequency of socio-demographic and behavioral factors in 711 patients with chronic HCV infection using data obtained from a prospective, multicenter cohort study, and to compare those factors in the cohort group with those in 206 patients with chronic liver diseases unrelated to HCV or hepatitis B virus infection (comparison group) at four university hospitals in Korea.

In this multicenter case-control study, we found that needle stick injury, dental procedure, tattoo, surgery, multiple sex partners, and blood transfusion more than 20 yr ago were significantly associated with chronic HCV infection in Korea. Factors for chronic HCV infection differed between male and female patients.

In our data, prevalence of HCV infection increased with age, peaking at over 60 yr. This age pattern is similar to prevalence data reported in Japan, China, Turkey, Spain, and Italy, but different from those in the United States, Australia, and northern Europe, where the peak prevalence was observed in subjects aged 30-49 yr (2, 18), suggesting that there may be different risk factors associated with HCV infection according to different geographic areas. Previous studies of HCV epidemiology in Korea reported that transfusion before 1992 was a strong factor for transmission (13, 14); however, findings with regard to other risk factors, such as injection drug use, needle stick injury, surgery, and tattooing have been limited (15-17). Moreover, those studies were performed more than 10 yr ago and were community-based whereas this one was a hospital-based.

Injection drug use (IDU) is one of the most important risk factors for HCV infection in many countries, especially among young adults (1). However, our study participants were relatively old and IDU has not been common in Korea. In our study, all 26 patients with a history of IDU were in the HCV group, and there was no IDU in the NBNC group (P = 0.004). Clearly, injection drug users in our study were more likely to have HCV infection; however, further investigation is necessary, as the rate of IDU is relatively low.

Whether acupuncture is a risk factor for HCV infection remains in dispute (7, 14, 19-21). In our study, the prevalence of acupuncture was high in both groups (HCV group; 82.1%, NBNC group; 74.8%), and was not associated with overall HCV infection (P = 0.09). However, in subgroup analysis, acupuncture was a risk factor for HCV infection among women, while it was not among men. This result was compatible with results of a previous study, which reported that the attributable risk fraction of acupuncture was 9% for men, and 55% for women (total 38%) among older adults (≥ 40 yr old) in Korea (17). Patterns of acupuncture may differ according to gender; however, it has not been evaluated in detail in this study.

Tattooing as a risk factor for HCV infection has also been controversial (5, 7, 13, 16, 22). In this study, people who had tattoos were about 2 times more likely to have HCV infection, compared to people who did not. However, in subgroup analysis, tattoo was an independent factor for HCV infection in men only, not in women, and men who had tattoos were 7 times more likely to have HCV infection, compared to those who did not. In this study, tattooing included eyebrow tattooing which was common in middle aged women for cosmetic purposes in Korea. Details on tattooing methods and tattooing areas were not examined in the study, but might be worthy of investigation in future studies.

The occupational exposure of HCV transmission occurs often in health care workers and individuals at risk (e.g., military settings, incarcerated in prison or jail, and end-stage renal disease) mostly via HCV-contaminated needle stick injuries (23, 24). In our study, needle stick injury was a strong independent risk factor for HCV infection (OR, 11.0). Further study on type of occupation (e.g., healthcare worker) or details on conditions at exposure is required. Nosocomial transmission is a well established route of HCV infection. A study in Italy showed that HCV transmission in a surgical setting was identified by administration of propofol in multi-dose vials (25). Findings from another study suggested that HCV transmission to five patients during open heart surgery occurred through an HCV-infected cardiac surgeon (26). However, surgical procedures as a risk factor for HCV infection are controversial in Korea (13, 15, 16). A community-based survey in Italy showed that dental procedures and use of glass syringes are associated with 2.5-fold and 1.9-fold increased risk for HCV infection (27), respectively, whereas other studies did not show a significant association (4, 5, 14, 16, 19). Our multivariate analysis showed that dental procedures and surgical procedures were significantly associated with HCV infection in Korea, whereas digestive endoscopy was not. A comprehensive review revealed only 35 cases of transmission via digestive endoscopic procedures in the prior decade, and the estimated HCV infection rate was 1 per ten million procedures (28, 29). Therefore, our data suggest that standard precautions in dental and surgical procedure should be improved in Korea.

HCV screening of blood donors began in Korea in 1992 (15), and transfusion was no longer a risk factor for HCV infection. Similarly, in our study, having a blood transfusion more than 20 yr ago was a significant risk factor for HCV infection, compared to having it within 20 yr. This finding is compatible with results of other studies in Korea (13) .

Sexual transmission of HCV occurs uncommonly, except among men having sex with men (1, 30, 31). A 10-yr prospective follow-up study found that the risk of HCV sexual transmission with monogamous couples was extremely rare (30). However, multiple sexual partners and early age (< 18 yr old) at the first sexual intercourse were independent predictors of anti-HCV positivity in a study conducted in the United States (32). According to our data, having multiple sexual partners (P = 0.002) and early age (< 18 yr old) at first sexual intercourse (13 of 379 in the HCV group vs 0 of 143 in the comparison group; P = 0.02, data not shown) were significantly associated with chronic HCV infection, which is consistent with findings from a US study (32).

Results have been controversial on intra-familial transmission of HCV. The prevalence of anti-HCV positivity among familial members living with patients with HCV ranges widely (from 0% to 27%) (1). Some studies have reported that anti-HCV positivity is highly correlated with duration of marriage and actual exposure (e.g., more frequent sexual contact and shared toothbrushes) (33, 34). In contrast, a study in Italy showed that among 1,379 household contacts of 585 HCV antibody-positive subjects, the prevalence of anti-HCV among household contacts was 7.3% (15.6% in spouses and 3.2% in other relatives), and the type of relationship (spouses vs other relatives), rather than years of marriage (≤ 20 yr vs > 20 yr) was an independent predictor of anti-HCV positivity among household contacts (35). In the current study, familial contact with an HCV positive patient was not a significant risk factor for HCV infection (P = 0.327, data not shown). This result may be related to the nature of the patients in our control group, who were mostly diagnosed with alcoholic liver disease, hemangioma, or hepatic cysts, which are associated with genetic factors.

This study had several limitations. First, for the comparison group patients we recruited patients who visited the same hospitals because of the chronic liver diseases caused by other than hepatitis B or C, so that they were not a community-based or liver disease-free control population. However, a survey of patients with liver diseases in the same clinic may have reduced recall bias during the questionnaire survey. Second, a significant difference in sample size was observed between the HCV group and the comparison groups. The reason was that the questionnaire survey was time consuming, and many patients with liver disease not related to HCV did not agree to participate in this study. Third, some patients did not want to answer private questions, such as those pertaining to sexual relationships, which resulted in missing data. The fundamental limitation was that a previous exposure history to the risk factors does not indicate a cause of HCV infection.

In conclusion, this study showed that the major risk factors for chronic HCV infection are closely related to conventional or alterative healthcare procedures and multiple sexual partners in Korea where intravenous drug use is uncommon. Therefore, standard precautions during invasive procedures in the healthcare setting and reinforced public education on risky behaviors are required to prevent HCV infection.