eMJA: Thomson et al., The prevalence of hepatitis C in patients admitted with acute hepatitis to Fairfield Infectious Diseases Hospital, 1971-1975

The prevalence of hepatitis C in patients admitted with acute hepatitis to Fairfield Infectious Diseases Hospital, 1971-1975

Jennifer A Thomson, Alison J Rodger, Sandra C Thompson, Damien Jolley, Amanda Byrne, Susan J Best and Nick Crofts

MJA 1998; 169: 360-363

Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details
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Abstract
Objective: To identify and determine trends in the prevalence of hepatitis C virus (HCV) antibody in stored sera from 1971 to 1975 and to determine associations with HCV seropositivity, including markers for other hepatitis infections and possible routes of transmission.
Design: A retrospective cross-sectional study.
Patients and setting: 1511 adults admitted to Fairfield Infectious Diseases Hospital, Victoria, with a clinical and biochemical diagnosis of hepatitis between 1 January 1971 and 31 December 1975.
Main outcome measures: Prevalence over study period of hepatitis A virus antibody (anti-HAV) IgM, hepatitis B core antibody (anti-HBc), hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) in stored sera; sociodemographic data and risk factors for blood-borne viruses documented in original medical records.
Results: Anti-HCV was detected in 17% of adults admitted with hepatitis from 1971 through 1975. Prevalence increased significantly over this period. Most cases were in young men who had a history of injecting drug use. HCV seropositivity was also significantly associated with markers for hepatitis B infection.
Conclusions: Given the 20-30-year period between infection with hepatitis and the development of liver disease, our findings predict significant liver-related morbidity in Australia in the next decade. The increase in prevalence over the five years studied suggests rapid spread of HCV through susceptible populations, principally injecting drug users.
Introduction
Hepatitis C is an important public health problem in Australia. Approximately 150 000 people in this country are currently infected with the virus, predominantly as a result of injecting drug use.^1,2 Acute hepatitis C virus (HCV) infection is generally benign; less than 25% are estimated to be icteric.³ The main significance of HCV infection is that it is strongly associated with the development of chronic liver disease. After 20 to 30 years a significant proportion of those infected will have chronic hepatitis, cirrhosis, liver failure and primary hepatocellular carcinoma.⁴ In view of this 20-30-year latency period, estimating the prevalence of HCV in the Australian community during the early 1970s may give an indication of the morbidity to be expected from this infection over the next decade.
We thus aimed to determine the prevalence of hepatitis C antibody in stored sera from people with acute viral hepatitis admitted to Fairfield Infectious Diseases Hospital (FIDH), Victoria, from 1971 to 1975, to identify possible associations with HCV seropositivity and to detect trends in HCV prevalence over that time.
Methods
Ethical approval for the study was obtained from the ethics committees at FIDH and the Australian Institute of Health and Welfare. We chose the period 1971 to 1975 because systematic storage of sera began in 1971, the same year diagnostic coding was standardised at FIDH (with the introduction of International classification of diseases, ninth revision coding), and because a previous study had identified HCV antibody in stored sera from that time.⁵
We included all patients admitted to FIDH with biochemical and clinical evidence of hepatitis between 1 January 1971 and 31 December 1975. Those for whom there was no original serum sample for testing and those for whom medical records could not be found were excluded. Patients aged under 16 years at the time of admission were also excluded as they were generally admitted for hepatitis A infection, which was endemic at that time.⁶
Multiple serum samples had been stored for many patients. For each individual, we tested the last available serum sample associated with their final hepatitis admission and which was adequate for testing. Sera were tested for all hepatitis markers at the Victorian Infectious Diseases Reference Laboratory and the National Serology Reference Laboratory, Australia by the following commercially available immunoassays: hepatitis A virus antibody (anti-HAV) IgM, IMX assay and HAVAB M enzyme immunoassay; hepatitis B core antibody (HBcAb), CORAB radioimmunoassay; hepatitis B surface antigen (HBsAg), AUSRIA II radioimmunoassay; and hepatitis C antibody (HCVAb), second generation enzyme immunoassay (all assays manufactured by Abbott Diagnostics, Abbott Park, Illinois, USA). Results were designated reactive or non-reactive by the laboratories.
As previous studies of frozen sera stored for long periods suggested a stringent classification was required to avoid overestimating the prevalence of antibody to HCV,^7,8 we used twice the manufacturer's recommended cutoff (as recommended in the literature⁷) to further increase the specificity of the HCV antibody test. Individuals with weakly positive results (ie, a ratio of 1-2 of sample optical density determined by enzyme-linked immunosorbent assay [ELISA] to cutoff optical density) were recorded as equivocal and excluded to minimise misclassification bias.
Medical records were located and information collected on sociodemographics and risk factors for hepatitis. For patients with multiple admissions over the study period, information on risk factors was summarised from all admissions preceding the date of the last available serum sample.
We compared our test results for the stored serum samples with the original results recorded for HBsAg at the time the samples were taken using K ⁹ to measure agreement. In addition, we traced a subset of patients in 1996 and 1997 and obtained information on risk factors before their FIDH admission. Traced patients were also retested for hepatitis B and C markers in 1996 and 1997. The results of tests on their original stored serum samples were compared with these follow-up results for hepatitis C virus antibody (anti-HCV) and hepatitis B core antibody (anti-HBc).

Statistical analysis
We used the Statistical Package for Social Sciences (SPSS)¹⁰ for data analysis, which included descriptive statistics, unpaired t test, chi-squared test, Fisher's exact test, chi-squared test for trend, and measures of risk and agreement.
Results
Patients aged over 16 and admitted to FIDH with hepatitis during the study period numbered 1798. Medical records were found for 1737 (97%) and 5% were noted to have been admitted with hepatitis more than once over the study period. Serum specimens were found for 1559 of these patients (90%) and testing for all the measured hepatitis markers was completed for 1511 (87%). We were able to trace a subset of 161 patients for follow-up in 1996 and 1997.
Box 3

The distribution of optical density ratios indicating anti-HCV status for the 1511 patients in the study is shown in Box 1. Seven per cent (99) had equivocal anti-HCV results and were excluded. Of the remaining 1412, 17% (238) were anti-HCV positive. Only 15% (37) of those who were anti-HCV positive had no evidence of other hepatitis markers. Those who were anti-HCV positive were significantly more likely to have markers for hepatitis B virus (Box 2), and the sensitivity and specificity of anti-HBc as a surrogate marker for HCV infection were 77% and 57%, respectively.
Box 3
The trends in prevalence of each of the measured hepatitis markers were significant (P < 0.05). The prevalence of anti-HCV increased fourfold, with the biggest increase between 1974 and 1975. The prevalence of anti-HBc and HBsAg also increased, while the prevalence of anti-HAV IgM declined (Box 3). In patients who were HCV seropositive, the prevalence of markers of hepatitis A and B did not change significantly over the study period.
Box 3

Validation of serological tests
For the 161 patients we traced, comparing the results of serological testing of their stored sera for anti-HBc and anti-HCV with those of follow-up tests in 1997 showed good overall agreement, with complete agreement for anti-HBc of 91% (K, 0.79; 95% CI, 0.67-0.91) and, for anti-HCV, of 88% (K, 0.74; 95% CI, 0.66-0.82).
For all patients, there was moderate agreement between HBsAg results recorded at the time of original admission and our results for the stored sera, with complete agreement for 65% (K, 0.58; 95%CI, 0.43-0.72).

Sociodemographic data and risk behaviours
Sociodemographic data were available from medical case records for all patients. The 238 individuals who were positive for anti-HCV were significantly younger than those who were anti-HCV negative (mean age at time of original admission, 22 years; SD, 5.3 years v. 29.5 years; SD, 12 years; P < 0.001). Anti-HCV-positive individuals were also significantly more likely to have been born in Australia (80% v. 69%; RR, 1.5; 95% CI, 1.4-1.8; P < 0.001) and to be male (62% v. 52%; RR, 1.4; 95% CI, 1.1-1.9; P < 0.001).
Information on risk factors was incompletely recorded in medical records. Only 40% had information recorded for injecting drug use, 69% for contact with someone with hepatitis, 36% for transfusion, 15% for tattooing and 11% for travel.
A history of injecting drug use and of contact with someone with hepatitis were the only risk factors significantly associated with HCV seropositivity (Box 2). There was good agreement between original records of injecting drug use in case records on admission and follow-up information obtained from the 161 patients traced in 1996 and 1997 (k, 0.83; 95% CI, 0.74-0.92).
Discussion
Our findings confirm the presence of anti-HCV among adults admitted with acute hepatitis to FIDH in Victoria in the early 1970s and also that its prevalence increased markedly from 1971 through 1975. Most cases were in young men who had a history of injecting drug use.
Most individuals with HCV appear to have been admitted because of subsequent infection with hepatitis A or B. While the actual proportion is unclear, it is likely to be significant as only 16% of HCV-seropositive individuals had no evidence of other acute hepatitis markers. As this implies that individuals with subclinical acute HCV infection were admitted and therefore included in the study, the HCV seropositive group would appear to be reasonably representative of community-acquired HCV infection in Melbourne in the 1970s. The significant association between the presence of HCV antibody and documented contact with a person with clinical hepatitis infection probably results from a spurious association with the hepatitis A or hepatitis B infection that precipitated admission. This also suggests that those infected with HCV were likely to have risk behaviours that exposed them to other hepatitis viruses, in particular to hepatitis B.
Significant misclassification of hepatitis status appears unlikely as there was moderate to good agreement between original results for hepatitis A and B with our results. In addition, we used a more stringent cutoff to classify anti-HCV status, to increase specificity and reduce misclassification bias. Another source of potential bias in our study was loss of samples as a result of our exclusion criteria, but given the large sample size this should not have significantly affected our findings.
The risk factor information in the original case records was also incomplete and may have been subject to bias. However, the results of follow-up assessment of risk factors in patients we were able to trace equate well with risk factor information documented at the time of original admissions, in particular the presence or absence of a history of injecting drug use. In addition, the association between injecting drug use and HCV seropositivity -- documented in many other studies in the 1990s^1,2,11-14 -- was very clear.
We did not identify the presence of tattoos and a history of blood transfusion as significant risk factors for HCV seropositivity, and this probably reflects the low prevalence of HCV in the general population in the 1970s.
The significant increase in the prevalence of HCV seropositivity over the five-year study period suggests that infection became firmly established within the Australian community, particularly the injecting drug user population, as early as the mid 1970s. Most of the estimated 150 000 people in Australia currently infected with HCV are thought to have become infected in the past two decades, implying that the population of injecting drug users expanded dramatically in the late 1970s and early 1980s.¹ Our finding of a twofold increase in the recording of injecting drug use among patients admitted with viral hepatitis from 1971 through 1975 supports this.
Given the 20-30-year latency period before the development of liver-related complications, it is likely that the rapid increase in prevalence of HCV infection from the mid 1970s will translate into a rapid increase in HCV-positive individuals presenting with liver disease over the next decade. Health service planning and resource allocation should take this into account.
Further research is now urgently required on the natural history of community-acquired, as opposed to transfusion-acquired, HCV infection in the Australian population and on factors that predict the development of hepatic sequelae.
Acknowledgements
We thank Anna Lanigan (MBCMR), Dr Alan Breschkin, Dr Mike Catton and Associate Professor Steven Locarnini (Victorian Infectious Diseases Reference Laboratory) and Dr Elizabeth M Dax (National Serology Reference Laboratory, Australia). The National Health and Medical Research Council (NHMRC) Public Health and Development Committee provided funding for the study, and Dr J Thomson was an NHMRC PHRDC Research Fellow. Dr Nick Crofts was funded from the Research Fund of the Macfarlane Burnet Centre and Dr Alison Rodger partly funded by the Victorian Health Promotion Foundation.
References

Crofts N, Jolley D, Kaldor J, et al. Epidemiology of hepatitis C virus infection among injecting drug users in Australia. J Epidemiol Community Health 1997; 51: 692-697.
MacDonald M, Crofts N, Kaldor J. Transmission of hepatitis C virus rates, routes, and cofactors. Epidemiol Rev 1996; 18: 137-148.
Alter HJ. To C or not to C? These are the questions. Blood 1995; 85: 1681-1695.
Seeff L. Natural history of Hepatitis C. Hepatology 1997; 26: 21-28.
Moaven L, Crofts N, Locarnini SA. Hepatitis C virus infection in Victorian injecting drug users in 1971. Med J Aust 1993; 158: 574.
Lehmann NI, Gust ID. The prevalence of antibody to hepatitis A virus in two populations in Victoria. Med J Aust 1977; 2: 731-732.
Lok AS, Ma OC, Chan TM, et al. Overestimation of the prevalence of antibody to hepatitis C virus in retrospective studies on stored sera. Hepatology 1991; 14: 756-762.
Moaven L, Cunningham T. Hepatitis C serology. Aust Microbiologist 1994; 12: 321-323.
Fleiss J. Statistical methods for rates and proportions. 2nd ed. London: Wiley; 1981.
SPSS [computer program]. Version 8. Chicago, Ill.: SPSS Inc, 1998.
Van Beek I, Buckley R, Stewart M, et al. Risk factors for hepatitis C virus infection among injecting drug users in Sydney. Genitourin Med 1994; 70: 321-324.
Crofts N, Aitken, CK. Incidence of and risk behaviours for blood-borne viruses in a cohort of injecting drug users in Victoria, 1990-1995. Med J Aust 1997; 167: 17-20.
Galeazzi B, Tufano A, Barbierato E, et al. Hepatitis C virus infection in Italian intravenous drug users: epidemiological and clinical aspects. Liver 1995; 15: 209-212.
Van den Hoek JA, van Haastrecht HJ, Goudsmit J, et al. Prevalence, incidence, and risk factors of hepatitis C virus infection among drug users in Amsterdam. J Infect Dis 1990; 162: 823-826.

(Received 3 Feb, accepted 3 Aug, 1998)

Authors' details

Epidemiology and Social Research Unit, The Macfarlane Burnet Centre for Medical Research, Melbourne, VIC.
Jennifer A Thomson, PhD, FAFPHM, Research Fellow;
Alison J Rodger, MRCP(UK), MFPHM(UK), Research Fellow;
Sandra C Thompson, PhD, FAFPHM, Research Associate;
Amanda Byrne, BSc(Hons), MSc, Research Assistant;
Nick Crofts, MPH, FAFPHM, Head.

Department of Public Health & Community Medicine, The University of Melbourne, Melbourne, VIC.
Damien Jolley, MSc(Epidemiol), MSc(Stats), Senior Lecturer in Epidemiology and Biostatistics.

National Serology Reference Laboratory, Australia, Melbourne, VIC.
Susan J Best, DipMedTech, Senior Scientist.

Reprints will not be available from the authors.
Correspondence: Dr A J Rodger, The Macfarlane Burnet Centre for Medical Research, PO Box 254, Fairfield, VIC 3078.
E-mail: rodgerATburnet.edu.au

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Abstract	*Objective:* To identify and determine trends in the prevalence of hepatitis C virus (HCV) antibody in stored sera from 1971 to 1975 and to determine associations with HCV seropositivity, including markers for other hepatitis infections and possible routes of transmission. *Design:* A retrospective cross-sectional study. *Patients and setting:* 1511 adults admitted to Fairfield Infectious Diseases Hospital, Victoria, with a clinical and biochemical diagnosis of hepatitis between 1 January 1971 and 31 December 1975. *Main outcome measures:* Prevalence over study period of hepatitis A virus antibody (anti-HAV) IgM, hepatitis B core antibody (anti-HBc), hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) in stored sera; sociodemographic data and risk factors for blood-borne viruses documented in original medical records. *Results:* Anti-HCV was detected in 17% of adults admitted with hepatitis from 1971 through 1975. Prevalence increased significantly over this period. Most cases were in young men who had a history of injecting drug use. HCV seropositivity was also significantly associated with markers for hepatitis B infection. *Conclusions:* Given the 20-30-year period between infection with hepatitis and the development of liver disease, our findings predict significant liver-related morbidity in Australia in the next decade. The increase in prevalence over the five years studied suggests rapid spread of HCV through susceptible populations, principally injecting drug users.
Introduction	Hepatitis C is an important public health problem in Australia. Approximately 150 000 people in this country are currently infected with the virus, predominantly as a result of injecting drug use.^1,2 Acute hepatitis C virus (HCV) infection is generally benign; less than 25% are estimated to be icteric.³ The main significance of HCV infection is that it is strongly associated with the development of chronic liver disease. After 20 to 30 years a significant proportion of those infected will have chronic hepatitis, cirrhosis, liver failure and primary hepatocellular carcinoma.⁴ In view of this 20-30-year latency period, estimating the prevalence of HCV in the Australian community during the early 1970s may give an indication of the morbidity to be expected from this infection over the next decade. We thus aimed to determine the prevalence of hepatitis C antibody in stored sera from people with acute viral hepatitis admitted to Fairfield Infectious Diseases Hospital (FIDH), Victoria, from 1971 to 1975, to identify possible associations with HCV seropositivity and to detect trends in HCV prevalence over that time.
Methods	Ethical approval for the study was obtained from the ethics committees at FIDH and the Australian Institute of Health and Welfare. We chose the period 1971 to 1975 because systematic storage of sera began in 1971, the same year diagnostic coding was standardised at FIDH (with the introduction of International classification of diseases, ninth revision coding), and because a previous study had identified HCV antibody in stored sera from that time.⁵ We included all patients admitted to FIDH with biochemical and clinical evidence of hepatitis between 1 January 1971 and 31 December 1975. Those for whom there was no original serum sample for testing and those for whom medical records could not be found were excluded. Patients aged under 16 years at the time of admission were also excluded as they were generally admitted for hepatitis A infection, which was endemic at that time.⁶ Multiple serum samples had been stored for many patients. For each individual, we tested the last available serum sample associated with their final hepatitis admission and which was adequate for testing. Sera were tested for all hepatitis markers at the Victorian Infectious Diseases Reference Laboratory and the National Serology Reference Laboratory, Australia by the following commercially available immunoassays: hepatitis A virus antibody (anti-HAV) IgM, IMX assay and HAVAB M enzyme immunoassay; hepatitis B core antibody (HBcAb), CORAB radioimmunoassay; hepatitis B surface antigen (HBsAg), AUSRIA II radioimmunoassay; and hepatitis C antibody (HCVAb), second generation enzyme immunoassay (all assays manufactured by Abbott Diagnostics, Abbott Park, Illinois, USA). Results were designated reactive or non-reactive by the laboratories. As previous studies of frozen sera stored for long periods suggested a stringent classification was required to avoid overestimating the prevalence of antibody to HCV,^7,8 we used twice the manufacturer's recommended cutoff (as recommended in the literature⁷) to further increase the specificity of the HCV antibody test. Individuals with weakly positive results (ie, a ratio of 1-2 of sample optical density determined by enzyme-linked immunosorbent assay [ELISA] to cutoff optical density) were recorded as equivocal and excluded to minimise misclassification bias. Medical records were located and information collected on sociodemographics and risk factors for hepatitis. For patients with multiple admissions over the study period, information on risk factors was summarised from all admissions preceding the date of the last available serum sample. We compared our test results for the stored serum samples with the original results recorded for HBsAg at the time the samples were taken using K ⁹ to measure agreement. In addition, we traced a subset of patients in 1996 and 1997 and obtained information on risk factors before their FIDH admission. Traced patients were also retested for hepatitis B and C markers in 1996 and 1997. The results of tests on their original stored serum samples were compared with these follow-up results for hepatitis C virus antibody (anti-HCV) and hepatitis B core antibody (anti-HBc). Statistical analysis We used the Statistical Package for Social Sciences (SPSS)¹⁰ for data analysis, which included descriptive statistics, unpaired t test, chi-squared test, Fisher's exact test, chi-squared test for trend, and measures of risk and agreement.
Results	Patients aged over 16 and admitted to FIDH with hepatitis during the study period numbered 1798. Medical records were found for 1737 (97%) and 5% were noted to have been admitted with hepatitis more than once over the study period. Serum specimens were found for 1559 of these patients (90%) and testing for all the measured hepatitis markers was completed for 1511 (87%). We were able to trace a subset of 161 patients for follow-up in 1996 and 1997. The distribution of optical density ratios indicating anti-HCV status for the 1511 patients in the study is shown in Box 1. Seven per cent (99) had equivocal anti-HCV results and were excluded. Of the remaining 1412, 17% (238) were anti-HCV positive. Only 15% (37) of those who were anti-HCV positive had no evidence of other hepatitis markers. Those who were anti-HCV positive were significantly more likely to have markers for hepatitis B virus (Box 2), and the sensitivity and specificity of anti-HBc as a surrogate marker for HCV infection were 77% and 57%, respectively.

	The trends in prevalence of each of the measured hepatitis markers were significant (P < 0.05). The prevalence of anti-HCV increased fourfold, with the biggest increase between 1974 and 1975. The prevalence of anti-HBc and HBsAg also increased, while the prevalence of anti-HAV IgM declined (Box 3). In patients who were HCV seropositive, the prevalence of markers of hepatitis A and B did not change significantly over the study period. Validation of serological tests For the 161 patients we traced, comparing the results of serological testing of their stored sera for anti-HBc and anti-HCV with those of follow-up tests in 1997 showed good overall agreement, with complete agreement for anti-HBc of 91% (K, 0.79; 95% CI, 0.67-0.91) and, for anti-HCV, of 88% (K, 0.74; 95% CI, 0.66-0.82). For all patients, there was moderate agreement between HBsAg results recorded at the time of original admission and our results for the stored sera, with complete agreement for 65% (K, 0.58; 95%CI, 0.43-0.72). Sociodemographic data and risk behaviours Sociodemographic data were available from medical case records for all patients. The 238 individuals who were positive for anti-HCV were significantly younger than those who were anti-HCV negative (mean age at time of original admission, 22 years; SD, 5.3 years v. 29.5 years; SD, 12 years; P < 0.001). Anti-HCV-positive individuals were also significantly more likely to have been born in Australia (80% v. 69%; RR, 1.5; 95% CI, 1.4-1.8; P < 0.001) and to be male (62% v. 52%; RR, 1.4; 95% CI, 1.1-1.9; P < 0.001). Information on risk factors was incompletely recorded in medical records. Only 40% had information recorded for injecting drug use, 69% for contact with someone with hepatitis, 36% for transfusion, 15% for tattooing and 11% for travel. A history of injecting drug use and of contact with someone with hepatitis were the only risk factors significantly associated with HCV seropositivity (Box 2). There was good agreement between original records of injecting drug use in case records on admission and follow-up information obtained from the 161 patients traced in 1996 and 1997 (k, 0.83; 95% CI, 0.74-0.92).
Discussion	Our findings confirm the presence of anti-HCV among adults admitted with acute hepatitis to FIDH in Victoria in the early 1970s and also that its prevalence increased markedly from 1971 through 1975. Most cases were in young men who had a history of injecting drug use. Most individuals with HCV appear to have been admitted because of subsequent infection with hepatitis A or B. While the actual proportion is unclear, it is likely to be significant as only 16% of HCV-seropositive individuals had no evidence of other acute hepatitis markers. As this implies that individuals with subclinical acute HCV infection were admitted and therefore included in the study, the HCV seropositive group would appear to be reasonably representative of community-acquired HCV infection in Melbourne in the 1970s. The significant association between the presence of HCV antibody and documented contact with a person with clinical hepatitis infection probably results from a spurious association with the hepatitis A or hepatitis B infection that precipitated admission. This also suggests that those infected with HCV were likely to have risk behaviours that exposed them to other hepatitis viruses, in particular to hepatitis B. Significant misclassification of hepatitis status appears unlikely as there was moderate to good agreement between original results for hepatitis A and B with our results. In addition, we used a more stringent cutoff to classify anti-HCV status, to increase specificity and reduce misclassification bias. Another source of potential bias in our study was loss of samples as a result of our exclusion criteria, but given the large sample size this should not have significantly affected our findings. The risk factor information in the original case records was also incomplete and may have been subject to bias. However, the results of follow-up assessment of risk factors in patients we were able to trace equate well with risk factor information documented at the time of original admissions, in particular the presence or absence of a history of injecting drug use. In addition, the association between injecting drug use and HCV seropositivity -- documented in many other studies in the 1990s^1,2,11-14 -- was very clear. We did not identify the presence of tattoos and a history of blood transfusion as significant risk factors for HCV seropositivity, and this probably reflects the low prevalence of HCV in the general population in the 1970s. The significant increase in the prevalence of HCV seropositivity over the five-year study period suggests that infection became firmly established within the Australian community, particularly the injecting drug user population, as early as the mid 1970s. Most of the estimated 150 000 people in Australia currently infected with HCV are thought to have become infected in the past two decades, implying that the population of injecting drug users expanded dramatically in the late 1970s and early 1980s.¹ Our finding of a twofold increase in the recording of injecting drug use among patients admitted with viral hepatitis from 1971 through 1975 supports this. Given the 20-30-year latency period before the development of liver-related complications, it is likely that the rapid increase in prevalence of HCV infection from the mid 1970s will translate into a rapid increase in HCV-positive individuals presenting with liver disease over the next decade. Health service planning and resource allocation should take this into account. Further research is now urgently required on the natural history of community-acquired, as opposed to transfusion-acquired, HCV infection in the Australian population and on factors that predict the development of hepatic sequelae.
Acknowledgements	We thank Anna Lanigan (MBCMR), Dr Alan Breschkin, Dr Mike Catton and Associate Professor Steven Locarnini (Victorian Infectious Diseases Reference Laboratory) and Dr Elizabeth M Dax (National Serology Reference Laboratory, Australia). The National Health and Medical Research Council (NHMRC) Public Health and Development Committee provided funding for the study, and Dr J Thomson was an NHMRC PHRDC Research Fellow. Dr Nick Crofts was funded from the Research Fund of the Macfarlane Burnet Centre and Dr Alison Rodger partly funded by the Victorian Health Promotion Foundation.
References	Crofts N, Jolley D, Kaldor J, et al. Epidemiology of hepatitis C virus infection among injecting drug users in Australia. J Epidemiol Community Health 1997; 51: 692-697. MacDonald M, Crofts N, Kaldor J. Transmission of hepatitis C virus rates, routes, and cofactors. Epidemiol Rev 1996; 18: 137-148. Alter HJ. To C or not to C? These are the questions. Blood 1995; 85: 1681-1695. Seeff L. Natural history of Hepatitis C. Hepatology 1997; 26: 21-28. Moaven L, Crofts N, Locarnini SA. Hepatitis C virus infection in Victorian injecting drug users in 1971. Med J Aust 1993; 158: 574. Lehmann NI, Gust ID. The prevalence of antibody to hepatitis A virus in two populations in Victoria. Med J Aust 1977; 2: 731-732. Lok AS, Ma OC, Chan TM, et al. Overestimation of the prevalence of antibody to hepatitis C virus in retrospective studies on stored sera. Hepatology 1991; 14: 756-762. Moaven L, Cunningham T. Hepatitis C serology. Aust Microbiologist 1994; 12: 321-323. Fleiss J. Statistical methods for rates and proportions. 2nd ed. London: Wiley; 1981. SPSS [computer program]. Version 8. Chicago, Ill.: SPSS Inc, 1998. Van Beek I, Buckley R, Stewart M, et al. Risk factors for hepatitis C virus infection among injecting drug users in Sydney. Genitourin Med 1994; 70: 321-324. Crofts N, Aitken, CK. Incidence of and risk behaviours for blood-borne viruses in a cohort of injecting drug users in Victoria, 1990-1995. Med J Aust 1997; 167: 17-20. Galeazzi B, Tufano A, Barbierato E, et al. Hepatitis C virus infection in Italian intravenous drug users: epidemiological and clinical aspects. Liver 1995; 15: 209-212. Van den Hoek JA, van Haastrecht HJ, Goudsmit J, et al. Prevalence, incidence, and risk factors of hepatitis C virus infection among drug users in Amsterdam. J Infect Dis 1990; 162: 823-826. (Received 3 Feb, accepted 3 Aug, 1998)