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Prevalence and risk factors of hepatitis C among former blood donors in rural China

  • Author Footnotes
    1 Both authors contributed equally to this work.
    Changhong Huang
    Footnotes
    1 Both authors contributed equally to this work.
    Affiliations
    Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, No.155 Changbai Road, Beijing 102206, China
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  • Author Footnotes
    1 Both authors contributed equally to this work.
    Feng Qiu
    Footnotes
    1 Both authors contributed equally to this work.
    Affiliations
    Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, No.155 Changbai Road, Beijing 102206, China
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  • Minzhuo Guo
    Affiliations
    Beijing International Travel Healthcare Center, Beijing, China
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  • Yao Yi
    Affiliations
    Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, No.155 Changbai Road, Beijing 102206, China
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  • Liping Shen
    Affiliations
    Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, No.155 Changbai Road, Beijing 102206, China
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  • Feng Wang
    Affiliations
    Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, No.155 Changbai Road, Beijing 102206, China
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  • Zhiyuan Jia
    Affiliations
    Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, No.155 Changbai Road, Beijing 102206, China
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  • Jingchen Ma
    Affiliations
    Hebei Province Center for Disease Control and Prevention, Shijiazhuang, China
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  • Yuliang Zhao
    Affiliations
    Hebei Province Center for Disease Control and Prevention, Shijiazhuang, China
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  • Shuang Zhang
    Affiliations
    Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, No.155 Changbai Road, Beijing 102206, China
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  • Yong Zhang
    Correspondence
    Corresponding author. Tel.: +86 10 58900800 (S. Bi); +86 10 58900802 (Y. Zhang); fax: +86 10 58900806.
    Affiliations
    Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, No.155 Changbai Road, Beijing 102206, China
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  • Shengli Bi
    Correspondence
    Corresponding author. Tel.: +86 10 58900800 (S. Bi); +86 10 58900802 (Y. Zhang); fax: +86 10 58900806.
    Affiliations
    Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, No.155 Changbai Road, Beijing 102206, China
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  • Author Footnotes
    1 Both authors contributed equally to this work.
Open ArchivePublished:July 16, 2012DOI:https://doi.org/10.1016/j.ijid.2012.05.1035

      Summary

      Background

      Illegal commercial plasma and blood donation activities in the late 1980s and early 1990s caused a large number of hepatitis C virus (HCV) infections in rural areas of China.

      Methods

      A cross-sectional survey was carried out in 2008, in which all residents in a former blood donation village in rural Hebei Province were invited for a questionnaire interview and testing for HCV antibodies. Questionnaires were administered to collect information about their personal status and commercial blood donation history, and HCV antibodies were tested by enzyme immunoassay.

      Results

      Of 520 villagers who participated in the interviews, 236 (45.4%) reported a history of selling whole blood or plasma. HCV seropositivity was confirmed in 148/520 (28.5%) interviewees and 101/236 (42.8%) former commercial plasma and blood donors. Selling plasma was the strongest independent predictor of HCV seropositivity (p = 0.0037). Past history of an operation was also independently associated with HCV infection (p = 0.0270).

      Conclusions

      Unsafe practices during illegal plasma donation led to a high risk of HCV seropositivity for donors during the late 1980s and early 1990s. Many infected people suffered chronic hepatitis from that time onwards and urgently needed treatment and care.

      Keywords

      1. Introduction

      Hepatitis C virus (HCV) infection occurs worldwide. It is a major cause of chronic liver disease and the most common indication for liver transplantation.
      • Alter M.J.
      • Margolis H.S.
      • Krawczynski K.
      • Judson F.N.
      • Mares A.
      • Alexander W.J.
      • et al.
      The natural history of community acquired hepatitis C in the United States.
      • Lauer G.M.
      • Walker B.D.
      Hepatitis C virus infection.
      Although the prevalence varies broadly among geographic areas, it is estimated that there are 170 million HCV chronic carriers globally and the prevalence rates range between about 0.1% in countries such as Iceland and Norway to 18.1% in Egypt.
      Hepatitis C: global prevalence
      In China, a nationwide study conducted in 1992 revealed that HCV prevalence was 3.2% in China overall and 3.1% in rural China.
      • Xia G.L.
      • Liu C.B.
      • Cao H.L.
      • Bi S.L.
      • Zhan M.Y.
      • Su C.A.
      • et al.
      Prevalence of hepatitis B and C virus infections in the general Chinese population. Results from a nationwide cross-sectional seroepidemiologic study of hepatitis A, B, C, D, and E virus infections in China, 1992.
      Other smaller studies have reported HCV prevalence rates of 0–3% in rural populations from various Chinese provinces.
      • Shimbo S.
      • Zhang Z.W.
      • Gao W.P.
      • Hu Z.H.
      • Qu J.B.
      • Watanabe T.
      • et al.
      Prevalence of hepatitis B and C infection markers among adult women in urban and rural areas in Shaanxi Province, China.
      • Zhang Z.W.
      • Shimbo S.
      • Qu J.B.
      • Liu Z.M.
      • Cai X.C.
      • Wang L.Q.
      • et al.
      Hepatitis B and C virus infection among adult women in Jilin Province: China: an urban–rural comparison in prevalence of infection markers.
      • Qu J.B.
      • Zhang Z.W.
      • Shimbo S.
      • Watanabe T.
      • Nakatsuka H.
      • Matsuda-Inoguchi N.
      • et al.
      Urban–rural comparison of HBV and HCV infection prevalence in eastern China.
      HCV is most frequently transmitted by percutaneous exposure to infected blood or blood-derived body fluids, such as through transfusion of contaminated blood or blood products, nonsterile medical injections, or injecting drug use.
      • Thomas D.L.
      Hepatitis C epidemiologic quandaries.
      In China, illegal commercial plasma and blood collection activities were very common in the late 1980s and early 1990s before the national blood donation law was enacted. These illegal blood donations caused serious blood-borne HCV infections in some rural areas. The first recognized outbreak of HCV infection among plasma donors occurred in the late 1980s.
      • Sun Y.D.
      • Meng Z.D.
      • Wang S.Y.
      • Chen X.R.
      • Sun D.G.
      • Chen Z.
      • et al.
      Epidemiologic investigation on an outbreak of hepatitis C.
      Since then, cross-sectional studies have investigated HCV infection among former plasma or blood donors, in whom prevalence rates have varied from 9.6% to 72.8%.
      • Wang S.
      • Ding H.
      • Zhang H.
      Hepatitis C virus infection among the plasmapheresis donors.
      • Zhang Y.X.
      The prevalence of HCV, HIV and HBV among paid blood donors.
      • Sun Y.
      Epidemiological and serological study on hepatitis C virus infection in plasmapheresis donors.
      • Zhang S.Y.
      Conditional logistic regression analysis of the influential factors of HCV infection in one blood-donator aggregated village.
      • Zhang M.
      • Sun X.D.
      • Mark S.D.
      • Chen W.
      • Wong L.
      • Dawsey S.M.
      • et al.
      Hepatitis C virus infection, Linxian, China.
      In the present study, we performed a cross-sectional survey to investigate the prevalence and risk factors among residents in a former commercial blood donation village in Central China, where farming is the predominant occupation. The data derived could be used to provide basic information for the management and treatment of HCV carriers in order to reduce the transmission of HCV after blood donation.

      2. Methods

      2.1 Participants and samples

      A register of all residents of the study village was obtained from the local authorities during the preparatory study. Next, all the local residents of this village aged 1–91 years were invited to participate in the investigation during 2005–2006. The field study was conducted in the village clinic or village committee office. Standardized questionnaire-based interviews sought demographic, medical, and behavioral data, including plasma/blood donation history. Ten milliliters of venous blood was collected in a vacutainer containing sodium heparin for HCV antibody testing. The samples were stored at room temperature and transferred within 3 h to a field station for processing. Aliquots of plasma were stored at −40 °C until they were sent on dry ice to the Chinese Center for Disease Control and Prevention in Beijing. The study protocol was approved by the Institute of the Chinese Academy of Medical Sciences.

      2.2 Laboratory assays

      We tested the plasma specimens for HCV antibody by HCV version 3.0 enzyme immunoassay (EIA) (Ortho Diagnostics, Raritan, NJ, USA) in accordance with the manufacturer's instructions. Samples that were positive by HCV EIA were confirmed by HCV version 3.0 RIBA (Ortho Diagnostics).

      2.3 Statistical analysis

      A Chi-square test was used to calculate and compare the prevalence of viral infections among participants with different sociodemographic characteristics. Multivariate logistic regression analyses were undertaken to compare factors associated with HCV infection among all participants. The 95% confidence interval (CI) of the prevalence was calculated based on normal approximation to binomial distribution when that approximation held. All statistical analyses were done using SAS software version 8.0.

      3. Results

      3.1 Participation rate and sociodemographics of participants

      Of the 1109 villagers, 520 individuals participated in the interviews, contributed blood samples for HCV testing, and were thereby included in the analysis. The proportions of male and female participants were almost equal and their age distribution was 1–91 years. The mean age of the male participants was 45.11 ± 19.32 years and for the female participants was 45.24 ± 17.46 years. Non-participation was mainly because of out-migration of the villagers for a temporary job. All participants were of Han majority ethnicity.

      3.2 Commercial plasma/blood donation history

      Of the 520 participants, 236 (45.4%) had a history of selling plasma or blood in the village, where there had been an illegal commercial plasma collection center. The other 284 villagers had never sold plasma or blood. Among the donors, 117 individuals had sold only blood and five had sold only plasma. The remaining 114 had sold both blood and plasma, and accounted for 48.3% of all donors.

      3.3 HCV seroprevalence and risk factors for HCV seropositivity

      3.3.1 Seroprevalence of anti-HCV in all subjects stratified by sex, age, education, and blood donation experience

      HCV infection was detected in 148 (28.5%) of the 520 villagers; 70 were males and 78 were females. The prevalence did not differ meaningfully by sex (Chi-square = 0.3094, p = 0.5780), however the trend Chi-square test revealed that HCV seropositivity varied with age. The peak HCV seropositivity occurred in the 50–59 years age group.
      Our results indicated that there was a significant difference between educated and illiterate villagers with regard to HCV infection, but we found no difference with respect to the level of education attained by those who had been educated (primary school, middle school, or high school level); this proved that HCV seropositivity had no relationship with educational experience.
      Of the villagers who had sold blood or plasma, 101 were infected, whereas only 47 of those who had never sold blood or plasma were seropositive. HCV seroprevalence in donors was 2.6 times higher than in the villagers who had not sold blood or plasma. All of the results are shown in Table 1.
      Table 1Seroprevalence of anti-HCV in all subjects stratified by sex, age, education, and blood donation experience
      ParametersNumberHCV seropositivity, n (%)Chi-square valuep-Value
      Sex0.30940.578
       Male25670 (27.3)
       Female26478 (29.5)
      Age groups, years21.5842<0.0001
       1–19494 (8.2)
       20–29649 (14.1)
       30–39609 (15.0)
       40–4912943 (33.3)
       50–5911054 (49.1)
       60 or older10829 (26.9)
      Education4.3410.0372
       Educated38095 (25.0)
       Illiterate14053 (37.9)
      Educational experience0.57890.7487
       Illiterate14053 (37.9)
       Primary school17543 (24.6)
       Middle school16542 (25.5)
       High school4010 (25.0)
      Donation43.611<0.0001
       Donors236101 (42.8)
       Non-donors28447 (16.5)
      HCV, hepatitis C virus.

      3.3.2 HCV seroprevalence in donors of blood and plasma

      HCV seroprevalence was higher in the donors who had sold both blood and plasma than in those who had only sold blood. However, there was no significant difference in HCV infection between the donors who had sold both blood and plasma and those who had only sold plasma. The villagers who had only sold plasma were more likely to have become HCV-seropositive than those who had only sold blood. The results are shown in Table 2.
      Table 2HCV seroprevalence in donors of blood and plasma
      Type of donationHCV antibodyHCV seropositivity (%)Chi-square valuep-Value
      PositiveNegative
      Non-donors4723716.50.7150.3978
      Blood donation only189915.4
      Blood donation only189915.4
      p-Value calculated directly by Fisher's bilateral exact probability test.
      0.0037
      p-Value calculated directly by Fisher's bilateral exact probability test.
      Plasma donation only4180.0
      Plasma donation only4180.00.260.6101
      Both donation793569.3
      Non-donors4723716.5104.62<0.0001
      Both donation793569.3
      HCV, hepatitis C virus.
      a p-Value calculated directly by Fisher's bilateral exact probability test.

      3.3.3 HCV seroprevalence according to route of blood exposure

      Univariate analysis demonstrated that surgery was a greater risk factor for HCV infection than receiving a blood transfusion, acupuncture, dental extraction, or sharing a razor or toothbrush. The results are shown in Table 3.
      Table 3HCV seroprevalence according to route of blood exposure
      Risk factorsHCV antibodyTotalHCV seropositivity (%)Chi-square valuep-Value
      PositiveNegative
      Blood transfusion
      p-Value calculated directly by Fisher's bilateral exact probability test.
      0.3393
      p-Value calculated directly by Fisher's bilateral exact probability test.
       Yes23540.0
       No14636951528.3
      Operation4.89360.027
       Yes30477739.0
       No11832544326.6
      Acupuncture0.0460.8301
       Yes7162330.4
       No14135649728.4
      Dental extraction0.79060.3739
       Yes20406033.3
       No12833246027.8
      Razor share0.18330.6685
       Yes34742.9
       No14536851328.3
      Teeth-brush share
      p-Value calculated directly by Fisher's bilateral exact probability test.
      0.4383
      p-Value calculated directly by Fisher's bilateral exact probability test.
       Yes12333.3
       No14737051728.4
      HCV, hepatitis C virus.
      a p-Value calculated directly by Fisher's bilateral exact probability test.

      3.3.4 Multivariate logistic regression analysis of risk factors

      Multivariate logistic regression analysis suggested that plasma donation (odds ratio (OR) 33.200, 95% CI 1.284–858.446; p = 0.035) and whole blood donation (OR 34.626, 95% CI 2.167–553.272; p = 0.012) were highly associated with HCV seropositivity. The results are shown in Table 4.
      Table 4Multivariate logistic regression analysis of risk factors
      Variablep-ValueOR95% CI
      Age0.0240.8160.683–0.974
      Plasma donation0.03533.2001.284–858.446
      Plasma and blood donation0.01234.6262.167–553.272
      Operation0.3941.3630.669–2.777
      OR, odds ratio; 95% CI, 95% confidence interval.

      4. Discussion

      According to the national survey of HCV infection, the average seroprevalence was 3.2%,
      • Xia G.L.
      • Liu C.B.
      • Cao H.L.
      • Bi S.L.
      • Zhan M.Y.
      • Su C.A.
      • et al.
      Prevalence of hepatitis B and C virus infections in the general Chinese population. Results from a nationwide cross-sectional seroepidemiologic study of hepatitis A, B, C, D, and E virus infections in China, 1992.
      which means that >40 million Chinese people were HCV-seropositive. Another epidemiological investigation has indicated that HCV is highly prevalent in former illegal blood and plasma donors and that prevalence could be up to 8.2% in that population.
      • Ogarkov P.I.
      • Malyshev W.
      • Tokmakov V.S.
      • Smirnov A.V.
      Epidemiological features of virus hepatitis in the Russian army.
      In the present study, 520 residents were selected from a former blood donation village in Dazhang, Zhao County, Hebei Province. We found that HCV seroprevalence was 28.5% in all villagers and 42.8% in former commercial plasma/blood donors, prevalences that are higher than the previously reported average.
      • Ogarkov P.I.
      • Malyshev W.
      • Tokmakov V.S.
      • Smirnov A.V.
      Epidemiological features of virus hepatitis in the Russian army.
      The increased risk of HCV infection was mainly as a result of the illegal commercial plasma and blood collection activities in selected rural areas. In particular, the practice of pooling blood and reinfusing red blood cells into donors of the same blood types caused the rapid spread of HCV infection.
      • Sun Y.D.
      • Meng Z.D.
      • Wang S.Y.
      • Chen X.R.
      • Sun D.G.
      • Chen Z.
      • et al.
      Epidemiologic investigation on an outbreak of hepatitis C.
      There was no difference in HCV seropositivity according to sex, which suggests a similar sensitivity to HCV infection between men and women. Chi-square tests revealed that HCV seropositivity increased with age and reached a peak in the 50–59 years age group. In contrast, HCV seroprevalence was lower in those aged ≥60 years than in the 50–59 years age group, because participation in commercial blood donation mostly involved adults and adolescents at that time. This study was performed more than 10 years after the ban on illegal commercial blood donation, and most of the donors were aged >40 years. This could explain why the 50–59 years age group had a relatively higher HCV seropositivity.
      Although HCV is transmitted mainly through blood-to-blood contact and intravenous drug use is currently the dominant route of transmission in developed countries, in China as a developing country, nosocomial transmission of HCV is not an uncommon route of infection and may be greatly underestimated. That is why surgery was found to be the most important HCV risk factor in our study by univariate analysis.
      In both male and female subjects, selling plasma, older age, and surgery appeared to be associated with HCV infection. In the multivariate analyses to identify risk factors, selling plasma (OR 33.200; p = 0.035) and whole blood (OR 34.626; p = 0.012) were independently associated with HCV seropositivity.
      However, HCV seropositivity was 16.5% in those who had never sold blood or plasma, which is clearly higher than the average HCV seroprevalence in the Chinese population. This phenomenon was probably caused by other unusual routes of HCV transmission, such as mucosal exposure, sexual transmission, and perinatal exposure (mother to child).
      • Amin J.
      • Gidding H.
      • Gilbert G.
      • Backhouse J.
      • Kaldor J.
      • Dore G.
      • et al.
      Hepatitis C prevalence—a nationwide serosurvey.
      • Law M.G.
      • Dore G.J.
      • Bath N.
      • Thompson S.
      • Crofts N.
      • Dolan K.
      • et al.
      Modelling hepatitis C virus incidence, prevalence and long-term sequelae in Australia, 2001.
      • Dominguez A.
      • Bruguera M.
      • Vidal J.
      • Plans P.
      • Salleras L.
      Community-based seroepidemiological survey of HCV infection in Catalonia, Spain.
      For example, the spouse of an HCV carrier was much more likely to be infected, and the child of an HCV-infected mother was also at higher risk.
      In summary, HCV is now common in this selected rural Chinese community and the public health impact of the high prevalence of HCV infection may be substantial. HCV is an important cause of end-stage liver disease and hepatocellular carcinoma, and it can act synergistically with hepatitis B virus infection,
      • Donato F.
      • Boffetta P.
      • Puoti M.
      A meta-analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma.
      which is endemic in China. Future studies should examine the prevalence of blood-borne viruses in other parts of China, how these viruses are transmitted, and the resulting health effects. Efforts to halt the transmission of HCV and other blood-borne viruses in rural China should be a top public health priority.

      Acknowledgements

      This work was supported by a grant from the Major Science and Technology Project for Infectious Disease. The authors express their sincere thanks to all members of the epidemic prevention station of Zhengding County for their support during the collection of samples.
      Conflict of interest: The authors declare that they have no competing interests.

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