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

BackgroundChronic 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.MethodsWe 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.ResultsAlthough 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.ConclusionsIn studies of fibrosis progression, 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

Stage-specific mortality of Calanus spp. under different predation regimes

We have applied the population surface method to estimate the mortality rates of eggs, nauplii, and copepodids of Calanus spp. in two Norwegian fjords with contrasting predator guilds. Efforts were concentrated in Lurefjorden on the western coast (sampled weekly from late February to mid-June), an unusual fjord dominated by invertebrate (tactile) planktivores. In addition, monthly sampling in Sørfjorden was carried out for comparisons. The latter fjord resembles most Western Norwegian fjords in that it contains populations of vertebrate (visual) planktivores but lower abundance of the invertebrate planktivores. In Lurefjorden, mortality of Calanus spp. was high early in life (∼0.35 d-1), but significantly lower (∼0.00 d-1) in the early copepodid stages. In Sørfjorden, mortality was rather uniform throughout ontogeny (∼0.08 d-1). The noted differences are consistent with different patterns of selective predation between the two fjords. Visual predation in Sørfjorden gave rise to persistent high mortality over the life cycle. Tactile predation in Lurefjorden gave rise to a concave mortality curve for the later developmental stages. Our results indicate that mortality patterns suffered by natural zooplankton populations may differ greatly over short geographical distances, and we suggest that the predator community and mortality patterns must be considered when addressing the spatial and temporal dynamics of zooplankton populations