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Estimating past hepatitis C infection risk from reported risk factor histories: implications for imputing age of infection and modeling fibrosis progression.

Bacchetti P, Tien PC, Seaberg EC, O'Brien TR, Augenbraun MH, Kral AH, Busch MP, Edlin BR - BMC Infect. Dis. (2007)

Bottom Line: Chronic hepatitis C virus infection is prevalent and often causes hepatic fibrosis, which can progress to cirrhosis and cause liver cancer or liver failure.We sought to examine the accuracy of such imputation and implications for modeling factors that influence progression rates.The models presented here can provide the inputs needed by such methods.

View Article: PubMed Central - HTML - PubMed

Affiliation: Box 0560, Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143, USA. peter@biostat.ucsf.edu

ABSTRACT

Background: Chronic hepatitis C virus infection is prevalent and often causes hepatic fibrosis, which can progress to cirrhosis and cause liver cancer or liver failure. Study of fibrosis progression often relies on imputing the time of infection, often as the reported age of first injection drug use. We sought to examine the accuracy of such imputation and implications for modeling factors that influence progression rates.

Methods: We analyzed cross-sectional data on hepatitis C antibody status and reported risk factor histories from two large studies, the Women's Interagency HIV Study and the Urban Health Study, using modern survival analysis methods for current status data to model past infection risk year by year. We compared fitted distributions of past infection risk to reported age of first injection drug use.

Results: Although injection drug use appeared to be a very strong risk factor, models for both studies showed that many subjects had considerable probability of having been infected substantially before or after their reported age of first injection drug use. Persons reporting younger age of first injection drug use were more likely to have been infected after, and persons reporting older age of first injection drug use were more likely to have been infected before.

Conclusion: In cross-sectional studies of fibrosis progression where date of HCV infection is estimated from risk factor histories, modern methods such as multiple imputation should be used to account for the substantial uncertainty about when infection occurred. The models presented here can provide the inputs needed by such methods. Using reported age of first injection drug use as the time of infection in studies of fibrosis progression is likely to produce a spuriously strong association of younger age of infection with slower rate of progression.

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Estimated biases resulting from imputing age at HCV infection as the age of first IDU. Bias is defined here as the reported age of first IDU minus the fitted mean from the multivariate models described by Figure 1 and Table 3. Circles below the horizontal line represent subjects who are likely to have been infected after their first IDU, while those above represent subjects likely to have been infected before their first IDU. We have added random numbers ranging from -0.4 to +0.4 to the integer ages in order to increase the visibility of distinct points. Included are HCV seropositive subjects with some history of IDU. a) WIHS data, n = 434; b) UHS data, n = 4047.
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Figure 2: Estimated biases resulting from imputing age at HCV infection as the age of first IDU. Bias is defined here as the reported age of first IDU minus the fitted mean from the multivariate models described by Figure 1 and Table 3. Circles below the horizontal line represent subjects who are likely to have been infected after their first IDU, while those above represent subjects likely to have been infected before their first IDU. We have added random numbers ranging from -0.4 to +0.4 to the integer ages in order to increase the visibility of distinct points. Included are HCV seropositive subjects with some history of IDU. a) WIHS data, n = 434; b) UHS data, n = 4047.

Mentions: Table 4 summarizes the models' fitted past risks for a number of situations and compares these to the reported age of first IDU, the usual imputed age at HCV infection. Scenarios 1–4 illustrate the impact of different ages at time of HCV antibody test and first IDU, while the remaining scenarios are based on extreme situations observed in the actual data sets. The alternatives at the bottom of the table illustrate the relatively minor impacts of different locations in WIHS and of male sex in UHS. Among all HCV seropositive subjects with IDU history, the median fitted probability that HCV infection occurred the year of first IDU or the next year was 0.77 for WIHS (range 0.23 to 0.93) and 0.56 for UHS (range 0.01 to 0.82). The lower values for UHS reflect its higher estimated background risk when reportedly not injecting and its smaller OR's for the effect of IDU (Table 3). When averaged over all subjects, mean bias was less than 1 year in both studies, because age of reported first IDU was sometimes too early and sometimes too late. There was, however, a strong correlation of bias with reported age of first IDU; the Pearson correlation was 0.78 (95% CI 0.73 to 0.81) in WIHS and 0.83 (95% CI 0.82 to 0.84) in UHS. Figure 2 illustrates this association, showing that those reporting first IDU before age 15 have average predicted ages of infection that are substantially after first IDU, while those reporting first IDU after age 30 have average predicted infection ages that can be many years before first reported IDU.


Estimating past hepatitis C infection risk from reported risk factor histories: implications for imputing age of infection and modeling fibrosis progression.

Bacchetti P, Tien PC, Seaberg EC, O'Brien TR, Augenbraun MH, Kral AH, Busch MP, Edlin BR - BMC Infect. Dis. (2007)

Estimated biases resulting from imputing age at HCV infection as the age of first IDU. Bias is defined here as the reported age of first IDU minus the fitted mean from the multivariate models described by Figure 1 and Table 3. Circles below the horizontal line represent subjects who are likely to have been infected after their first IDU, while those above represent subjects likely to have been infected before their first IDU. We have added random numbers ranging from -0.4 to +0.4 to the integer ages in order to increase the visibility of distinct points. Included are HCV seropositive subjects with some history of IDU. a) WIHS data, n = 434; b) UHS data, n = 4047.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2238758&req=5

Figure 2: Estimated biases resulting from imputing age at HCV infection as the age of first IDU. Bias is defined here as the reported age of first IDU minus the fitted mean from the multivariate models described by Figure 1 and Table 3. Circles below the horizontal line represent subjects who are likely to have been infected after their first IDU, while those above represent subjects likely to have been infected before their first IDU. We have added random numbers ranging from -0.4 to +0.4 to the integer ages in order to increase the visibility of distinct points. Included are HCV seropositive subjects with some history of IDU. a) WIHS data, n = 434; b) UHS data, n = 4047.
Mentions: Table 4 summarizes the models' fitted past risks for a number of situations and compares these to the reported age of first IDU, the usual imputed age at HCV infection. Scenarios 1–4 illustrate the impact of different ages at time of HCV antibody test and first IDU, while the remaining scenarios are based on extreme situations observed in the actual data sets. The alternatives at the bottom of the table illustrate the relatively minor impacts of different locations in WIHS and of male sex in UHS. Among all HCV seropositive subjects with IDU history, the median fitted probability that HCV infection occurred the year of first IDU or the next year was 0.77 for WIHS (range 0.23 to 0.93) and 0.56 for UHS (range 0.01 to 0.82). The lower values for UHS reflect its higher estimated background risk when reportedly not injecting and its smaller OR's for the effect of IDU (Table 3). When averaged over all subjects, mean bias was less than 1 year in both studies, because age of reported first IDU was sometimes too early and sometimes too late. There was, however, a strong correlation of bias with reported age of first IDU; the Pearson correlation was 0.78 (95% CI 0.73 to 0.81) in WIHS and 0.83 (95% CI 0.82 to 0.84) in UHS. Figure 2 illustrates this association, showing that those reporting first IDU before age 15 have average predicted ages of infection that are substantially after first IDU, while those reporting first IDU after age 30 have average predicted infection ages that can be many years before first reported IDU.

Bottom Line: Chronic hepatitis C virus infection is prevalent and often causes hepatic fibrosis, which can progress to cirrhosis and cause liver cancer or liver failure.We sought to examine the accuracy of such imputation and implications for modeling factors that influence progression rates.The models presented here can provide the inputs needed by such methods.

View Article: PubMed Central - HTML - PubMed

Affiliation: Box 0560, Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143, USA. peter@biostat.ucsf.edu

ABSTRACT

Background: Chronic hepatitis C virus infection is prevalent and often causes hepatic fibrosis, which can progress to cirrhosis and cause liver cancer or liver failure. Study of fibrosis progression often relies on imputing the time of infection, often as the reported age of first injection drug use. We sought to examine the accuracy of such imputation and implications for modeling factors that influence progression rates.

Methods: We analyzed cross-sectional data on hepatitis C antibody status and reported risk factor histories from two large studies, the Women's Interagency HIV Study and the Urban Health Study, using modern survival analysis methods for current status data to model past infection risk year by year. We compared fitted distributions of past infection risk to reported age of first injection drug use.

Results: Although injection drug use appeared to be a very strong risk factor, models for both studies showed that many subjects had considerable probability of having been infected substantially before or after their reported age of first injection drug use. Persons reporting younger age of first injection drug use were more likely to have been infected after, and persons reporting older age of first injection drug use were more likely to have been infected before.

Conclusion: In cross-sectional studies of fibrosis progression where date of HCV infection is estimated from risk factor histories, modern methods such as multiple imputation should be used to account for the substantial uncertainty about when infection occurred. The models presented here can provide the inputs needed by such methods. Using reported age of first injection drug use as the time of infection in studies of fibrosis progression is likely to produce a spuriously strong association of younger age of infection with slower rate of progression.

Show MeSH
Related in: MedlinePlus