The Risk of Hepatitis C Virus Infection Among Blood Donors in Osaka , Japan

To estimate the risk of hepatitis C virus (HCV) infection among blood donors, we conducted a retrospective cohort study with 448,020 HCV-seronegative donors who donated blood more than once between February 1992 and July 1997 in Osaka (a total of 2,676,738 allogeneic blood donations). The donors were divided into four age groups according to the age at the initial donation: Group A (16-24 years), Group B (25-34 years), Group C (35-49 years) and Group D (5064 years). Fifty-nine donors became infected with HCV among the 448,020 HCV-seronegative donors who donated blood more than once within a period of approximately five years. In a total of 1,095,668 person-years of observation (PYO), the incidence rate was 5.38 per 105 PYO, with the 95% confidence interval (95% C.I.) being 4.10 to 6.95. There was no significant difference in the incidence rate between males and females. Young donors between the ages of 16 and 24 (8.89; 95% C.I., 6.04 to 12.61) had a significantly higher incidence rate of HCV infection than donors between the ages of 35 and 49 (1.81; 0.67 to 3.95). The cumulative risk of HCV infection among donors between the ages of 16 and 64 was estimated to be 0.27% (95% C.I., 0.16 to 0.39) for males and 0.27% (95% C.I., 0.15 to 0.38) for females. Based on the recent age-specific incidence rate, the cumulative risk of HCV infection among blood donors was estimated to be about 0.3% in the Osaka district of Japan. The incidence rate differed among age groups, indicating that HCV infection is associated with age-related behaviors and the need for further epidemiological research towards the eradication of community-acquired HCV infection. J Epidemiol, 1998; 8 : 292-296.

The Risk of Hepatitis C Virus Infection Among Blood Donors in Osaka, Japan Hideo Tanaka 1, Hideaki Tsukuma 1, Yuji Hori 2 ,Toru Nakade 2, Hajime Yamano 2, Noriko Kinoshita 1, Akira Oshima1, and Hirotoshi Shibata 2 To estimate the risk of hepatitis C virus (HCV) infection among blood donors, we conducted a retrospective cohort study with 448,020 HCV-seronegative donors who donated blood more than once between February 1992 and July 1997 in Osaka (a total of 2,676,738 allogeneic blood donations).The donors were divided into four age groups according to the age at the initial donation: Group A (16-24 years), Group B (25-34 years), Group C (35-49 years) and Group D (50-64 years).Fifty-nine donors became infected with HCV among the 448,020 HCV-seronegative donors who donated blood more than once within a period of approximately five years.In a total of 1,095,668 person-years of observation (PYO), the incidence rate was 5.38 per 105 PYO, with the 95% confidence interval (95% C.I.) being 4.10 to 6.95.There was no significant difference in the incidence rate between males and females.Young donors between the ages of 16 and 24 (8.89; 95% C.I., 6.04 to 12.61) had a significantly higher incidence rate of HCV infection than donors between the ages of 35 and 49 (1.81; 0.67 to 3.95).The cumulative risk of HCV infection among donors between the ages of 16 and 64 was estimated to be 0.27% (95% C.I., 0.16 to 0.39) for males and 0.27% (95% C.I., 0.15 to 0.38) for females.Based on the recent age-specific incidence rate, the cumulative risk of HCV infection among blood donors was estimated to be about 0.3% in the Osaka district of Japan.The incidence rate differed among age groups, indicating that HCV infection is associated with age-related behaviors and the need for further epidemiological research towards the eradication of community-acquired HCV infection.J Epidemiol, 1998; 8 : 292-296.hepatitis C virus, blood donors, infection, cohort study Hepatitis C virus (HCV) is a blood-borne virus which causes a wide spectrum of liver diseases, ranging from acute hepatitis to hepatocellular carcinoma.
Parenteral infection through blood transfusion, intravenous drug abuse (IVDU) and tattoos, as well as occupational exposures to blood, have been welldefined as determinants of HCV transmission 1).However, these factors account for only 50-60% of acute hepatitis C in the United States 2), and only 40% of patients with HCV-related hepatocellular carcinoma had a history of blood transfusion in Japan 3).These findings have called much attention to other routes of transmission, such as inapparent parenteral, nosocomial or sexual exposure 4-9), although the rate of efficiency of such transmission is low.There is a relatively higher prevalence of HCV in Japan than in the world at large1,10) and there is an especially high prevalence in Osaka (more than 5% among donors in 55 to 64 year age) 11).The majority of HCV carriers in Osaka do not have a history of blood transfusion nor of high risk behaviors such as IVDU 12), suggesting that community-acquired HCV infection has been predominant in Osaka.There is no information regarding the incidence of HCV in the general population.
Consecutive screening data of HCV markers in voluntary blood donors are useful to estimate the incidence of HCV infection among the general population, which are considered to be healthy in general.There have been some cohort studies of blood donors in the United States 13), Japan 14) and Italy ls, but the number of cases in these reports is too small to draw conclusions regarding the demographic characteristics of the Anti-HCV seroconverters were defined as donors who became anti-HCV-positive at a subsequent donation.Based on the published data concerning the validity of this HCV screening for Japanese donors 17), we defined newly infected donors as seroconverters who met one of the following criteria: (1) blood anti-HCV titer on subsequent blood donations elevated to 2" or more (Criterion I) and (2) anti-HCV subsequently reactive up to 25~211 with a concomitant elevation of ALT to an abnormal range, (>36 K.U.) reaching more than twice as high as that of the initial donor blood (Criterion H).
Person-years were calculated from the date of the first donation to the date of the last donation for non-seroconverting donors, and from the date of the first donation to the midpoint between the last seronegative and the first seropositive donation for seroconverting donors.Incidence was expressed as the number of HCV seroconverters determined by the above criteria per 100,000 person-years.
Using the incidence rate, we calculated the cumulative risk of HCV infection among donors.Cumulative risk is the risk for an individual to develop the disease in question during a certain age period if no other cause of death intervenes.If the instantaneous incidence rate at an age t is given by I(t), then the cumulative risk between ages t1 and t2 is given by: The expression inside the exponential is closely approximated by the sum of the age-specific incidence rates for each year of age between t1 and t2.We used "I(t)" from age specific incidence rates of HCV infection among donors aged 16 to 64.It is given by: We used the SAS/PC statistical package (SAS Institute, Cary, NC) for data analysis.The 95% confidence interval was calculated based on the Poisson distribution.

RESULTS
Between February 1992 and July 1997 , 448,020 subjects made 1,962,106 blood donations.The average number of blood donations from a single donor was 4.38 (S.D. 5 .19,median 3).The mean duration of follow up among subjects by sex and age did not differ significantly.The number of donors newly infected with HCV who matched criterion I was 41 , while the number of donors newly infected with HCV who matched criterion II was 18.The screening results of six representative cases are shown in Table 1.Case 6 had the lowest variation in ALT value among the 18 donors meeting criterion Table 1.Screening data of six seroconverting blood donors diagnosed as newly infected case.*: The criterion for the diagnosis of HCV infection were described in the Methods section , II.Among the 59 seroconverters, 32 were male and 27 were female.The group between 16 and 24 years (Group A) comprised the greatest percentage (31 new cases; 52.5%) of those newly infected with HCV (Table 2).
The total number of person-years was 1,095,668 , and the incidence was 5.38 per 105 person-years of observation (PYO) (95% CI = 4.10-6.95)(Table 2).The incidence rate was highest in males in Group A and the lowest in Group C (35-49 yrs) for both males and females.The incidence rate in Group A (8.89 per 105 PYO, 95% CI= 6.04-12.61)was significantly higher than that in Group C (1.81 per 105 PYO, 95% CI= 0.67-

3.95).
Using the age-specific infection rate, the cumulative risk of HCV infection was calculated (Table 3).The cumulative risk of donors between the ages of 16 and 64 was low, about 0.27% in both males and females.

DISCUSSION
Our results showed that the crude HCV infection rates among blood donors in the Osaka area were 5.1 and 5.8 per 105 PYO for males and females, respectively.These values are similar to the incidence of seroconversion obtained by seven screening tests, including anti-HCV, in the United States 13).Sasaki et al 14) reported that the incidence rate of HCV infection among blood donors in Hiroshima was 1.78 per 105 PYO, suggesting there is geographical difference of HCV infection rate in Japan.Our results, however, may contain false-positive cases, since we did not confirm the 59 seroconverted blood donors by measuring their serum HCV-RNA.However, the tests used in our study have been shown to have a predictive positive value of 100% (120/120 cut off value: 212 ) 17).In addition, since we included the ALT test as an additional test in seroconvertors who had moderately increased its titer (25-11), the likelihood of false positivity should be minimal and should not substantially change the value for incidence.
The actual incidence rate of HCV infection in the general population in the Osaka area is considered to be higher than that among the population we examined because repeat blood donors usually receive fewer medical procedures and, therefore, are subjected to less risk of parenteral infection than those who do not donate blood.Also, the risk of infection via drugs and sexual transmission among non-donors may be higher than among repeat donors.In addition, those newly infected with acute hepatitis or experiencing symptoms of hepatitis are restricted from donating blood.
Although the incidence rate of HCV infection in the study subjects was substantially low, it differed among age groups.The incidence rate of HCV infection in Group A was significantly higher than that in Group C.Although the rate of sexual transmission of HCV has been reported to be low 19,20) , the significance of sexual transmission should not be neglected as a route of transmission of HCV among healthy people.Our study also showed the tendency that the incidence rate of HCV infection in Group D is higher than that Group C. According to epidemiological investigation of HCV in endemic areas of Japan, acupuncture using nonsterilized equipment should be considered as a possible route of transmission of HCV in the older age group 21).There is a possibility that transmission of HCV by Japanese traditional medical procedures in the older age groups may be significant.Our finding that transmission of HCV differs among age groups suggests that we may be able to reduce the incidence of HCV transmission by appropriate strategies targeted to specific age groups.
The present study suggests that the cumulative risk of HCV infection among blood donors between the ages of 16 and 64 in the Osaka area is about 0.3% in both sexes.The prevalence of anti -HCV-positive blood donors who donat-ed blood at ORCBC in 1992 was reported to be 10.0% and 7.9% in those from 60 to 64 years of age for males and females, respectively 10).These rates decreased in younger age groups, and the rates in the age group of 16 and 19 years were 0.31% and 0.20% for males and females, respectively 10).Post-transfusion HCV hepatitis has been nearly eradicated since the introduction of the anti-HCV screening test in Japan 11).Therefore, as long as the current low incidence of HCV is maintained in the general population, we expect that the number of HCV carriers will decrease with time.However, since the actual cumulative risk is considered to be higher than that which we obtained from the analysis of donor blood, an epidemiological study is necessary to find the route of infection of community-acquired HCV transmission to reduce the number of HCV carriers .Since the period between the time of infection and the time of appearance of crucial chronic liver diseases is about 20-30 years as, it is important to develop plans to prevent the transmission of HCV in young people.

Table 2 .
Incidence of HCV infection among blood donors in Osaka.