Limits...
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.

Show MeSH

Related in: MedlinePlus

Estimated effects of age and calendar year for the multivariate models of HCV infection risk. WIHS: solid lines; UHS: dashed lines. Vertical bars are pointwise 95% confidence intervals. a) Estimated odds ratios for age. The reference age is 30, where the odds ratio is 1.0 by definition. b) Estimated odds ratios for calendar year. The reference year is 1975, where the odds ratio is 1.0 by definition.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2238758&req=5

Figure 1: Estimated effects of age and calendar year for the multivariate models of HCV infection risk. WIHS: solid lines; UHS: dashed lines. Vertical bars are pointwise 95% confidence intervals. a) Estimated odds ratios for age. The reference age is 30, where the odds ratio is 1.0 by definition. b) Estimated odds ratios for calendar year. The reference year is 1975, where the odds ratio is 1.0 by definition.

Mentions: Multivariate models of HCV risk for WIHS and UHS are shown in Table 3 and Figure 1. The estimated background risk for these models was 0.0051 (95% CI 0.0028 to 0.0091) for WIHS and 0.034 (95% CI 0.021 to 0.055) for UHS. This is the fitted probability of being infected with HCV over the course of a year at age 30 in 1975 for a previously HCV-uninfected, (reportedly) non-injecting, HIV-uninfected Caucasian female in the San Francisco area. Fitted probabilities for other situations and types of subjects are obtained by applying the OR's shown in Table 3 and Figure 1 to these background rates. Both cohorts produced some qualitatively similar results, including decreased risk at younger ages and more recent calendar years, as well as highest risk in the reported first year of IDU. Despite these similarities, there were too many quantitatively substantial differences to permit a simple model of both studies pooled. These include the background risk when not injecting, the shape of the drop in risk as reported duration of IDU increases, the role of daily IDU, the strength of the influence of age, and racial/ethnic associations. The model shown in Figure 1b for UHS is a parametric spline with knots at 1980, 1990, and 1995, because this provided an improved fit to the data compared to a quadratic model (p = 0.0028), even though its overall shape is roughly quadratic. The other curves in Figure 1 are all quadratic, because these improved substantially over linear models (WIHS p = 0.0003 for age and p = 0.0054 for calendar year; UHS p = 0.018 for age), but parametric splines with up to 4 parameters did not appear to substantially improve the fits further (all p > 0.22).


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 effects of age and calendar year for the multivariate models of HCV infection risk. WIHS: solid lines; UHS: dashed lines. Vertical bars are pointwise 95% confidence intervals. a) Estimated odds ratios for age. The reference age is 30, where the odds ratio is 1.0 by definition. b) Estimated odds ratios for calendar year. The reference year is 1975, where the odds ratio is 1.0 by definition.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Estimated effects of age and calendar year for the multivariate models of HCV infection risk. WIHS: solid lines; UHS: dashed lines. Vertical bars are pointwise 95% confidence intervals. a) Estimated odds ratios for age. The reference age is 30, where the odds ratio is 1.0 by definition. b) Estimated odds ratios for calendar year. The reference year is 1975, where the odds ratio is 1.0 by definition.
Mentions: Multivariate models of HCV risk for WIHS and UHS are shown in Table 3 and Figure 1. The estimated background risk for these models was 0.0051 (95% CI 0.0028 to 0.0091) for WIHS and 0.034 (95% CI 0.021 to 0.055) for UHS. This is the fitted probability of being infected with HCV over the course of a year at age 30 in 1975 for a previously HCV-uninfected, (reportedly) non-injecting, HIV-uninfected Caucasian female in the San Francisco area. Fitted probabilities for other situations and types of subjects are obtained by applying the OR's shown in Table 3 and Figure 1 to these background rates. Both cohorts produced some qualitatively similar results, including decreased risk at younger ages and more recent calendar years, as well as highest risk in the reported first year of IDU. Despite these similarities, there were too many quantitatively substantial differences to permit a simple model of both studies pooled. These include the background risk when not injecting, the shape of the drop in risk as reported duration of IDU increases, the role of daily IDU, the strength of the influence of age, and racial/ethnic associations. The model shown in Figure 1b for UHS is a parametric spline with knots at 1980, 1990, and 1995, because this provided an improved fit to the data compared to a quadratic model (p = 0.0028), even though its overall shape is roughly quadratic. The other curves in Figure 1 are all quadratic, because these improved substantially over linear models (WIHS p = 0.0003 for age and p = 0.0054 for calendar year; UHS p = 0.018 for age), but parametric splines with up to 4 parameters did not appear to substantially improve the fits further (all p > 0.22).

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