Hepatology Baseline anti-HCV antibodies and ALT activity were deter- mined, but, as they were identical for the four strategies, they were not taken into account in this analysis. When the HCV RNA test was negative during follow-up, a second HCV RNA test was requested to confirm the absence of HCV infection, because undetectable HCV RNA at one time point does not exclude the possibility of HCV infection.19 20 When the HCV RNA test was positive, a second HCV RNA test was required before treatment administration. The present model-based study simulated the trajectory of 7300 HCV-seronegative HCWs (ie, number of HCWs percuta- neously exposed to anti-HCV antibody-positive source patients each year in France),1 who were followed from exposure to death. Model outcomes included the number of patients who developed chronic hepatitis C (CHC), number of incidents of CHC avoided by early therapy, lifetime quality-adjusted life years (QALYs), direct medical costs and incremental C/E ratios. The incremental C/E ratio was defined as the additional cost of a specific strategy compared with the next least expensive strategy, divided by its additional clinical benefit.21 We adopted a societal perspective considering everyone affected by the intervention and counting all significant health outcomes and costs that flow from it from the time of intervention to death.21 Future costs and clinical benefits were discounted at 3% per year.21 Costs were expressed in 2006 Euros (J1.00 = US$1.34 = £0.78, 17 October 2008). Model structure Follow-up strategies after occupational exposure The decision tree simulated four follow-up strategies after occupational exposures to HCV (Supplementary fig 1). The trajectory of HCWs through each strategy is described in detail in the legend of Supplementary fig 1. In brief, we modelled the trajectory of the HCWs in such a way that we were first able to estimate, based on the sensitivity of tests used for each strategy, the time to HCV positivity detection for that strategy. Next, in those in whom HCV transmission occurred, we were able to model the probability of hepatitis C spontaneous resolution, the benefit of treating acute hepatitis C earlier in the absence of the spontaneous resolution of the infection and the course of CHC disease in the absence of a response to acute hepatitis C treatment. Follow-up in the case where a treatment for acute hepatitis C was initiated Treatment for acute hepatitis C was administered for a duration of 6 months.22 A positive HCV RNA test at the end of treatment corresponded to non-response to treatment and the patient was considered to have CHC. For those with a negative HCV RNA test at the end of treatment, HCV RNA was tested again 6 months later. A positive test at that time corresponded to a relapse and the patient was considered to have CHC, whereas a negative test corresponded to a sustained viral response (SVR). The follow-up of treatment for acute hepatitis C consisted of three outpatients visits and three ALT measure- ments at 1, 3 and 6 months after the start of therapy, one HCV RNA test at the end of treatment and one 6 months later. CHC disease course Life expectancy, health-related quality of life and lifetime costs of patients with CHC were estimated from the study of San Miguel et al23 where the course of HCV disease was modelled in a cohort of Spanish patients with CHC, with a median age of 42 106 years, who had previously not responded to interferon (IFN). We used a study in which the course of patients who had not responded to antiviral therapy was modelled because in our analysis all HCWs with CHC had failed a first antiviral treatment for acute hepatitis C. In the study of San Miguel et al, patients received an additional course of standard IFN and ribavirin combination for 12 months and the course of the disease was simulated until death. Input data HCV transmission probability In the base case analysis, the average risk of HCV transmission after occupational exposure considered was 0.5%.11 17 In the sensitivity analysis, a lower and a higher risk were considered. We used data from a recent case–control study of risk factors for HCV transmission to estimate the risk of HCV transmission after occupational exposure according to the presence of one or several risk factors.18 We found that in the most favourable cases, superficial injuries corresponded to a low risk of 0.009%, whereas, in the least favourable, deep injuries with a hollow- bore needle in a vein or artery of a male HCW corresponded to a higher risk of 6.669%. Test sensitivity and specificity Test sensitivities were derived from knowledge of the time interval from HCV exposure to: (1) the appearance of anti-HCV antibodies with third-generation assays; (2) the elevation of ALT; and (3) HCV RNA detection (table 1). The mean interval to the appearance of anti-HCV antibodies was previously estimated at 66 days24 to 82 days.25 26 Mosley et al reported that the median latency period to an ALT elevation of .90 IU/l was 46 days.27 The interval between ALT elevation and anti-HCV antibody appearance is generally 1–2 weeks.28 The interval from HCV exposure to HCV RNA detection was reported to be 1– 2 weeks29 with a mean of 10 days.24 In this analysis, a normal distribution was chosen to model the distribution of the times to the appearance of anti-HCV antibodies and HCV RNA. An exponential function was chosen to model the time to ALT elevation, so that the cumulative probability of this elevation at month 6 was ,1, taking into account the possible fluctuation of ALT and the possible absence of detection of ALT elevation in some subjects. The derived sensitivities increased from 10.2% (range, 3.3–18.8%) at 1 month to 100% at 6 months for anti- HCV antibodies, from 36.8% (36.8–44.3%) to 93.6% (93.6– 100%) for ALT, and were 100% for HCV RNA detection. Specificities of 100% were assumed for anti-HCV antibody30–32 and HCV RNA detection.33 The specificity of the assay for ALT was derived from a study conducted in a population of Japanese male bank employees.34 In that study, the specificity of elevated ALT (.39 IU/l) was estimated at 86.3%. Acute hepatitis C treatment efficacy The French Haute Autorit´e en Sant´e (HAS) recommended treating acute hepatitis C with standard IFN or pegylated interferon monotherapy (PEG-IFN) (http://www.has-sante.fr/ portail/upload/docs/application/pdf/06-072_hepat-c_internet_- sans_liste.pdf).35 36 Recently, a randomised trial assessing the efficacy and timing of PEG-IFN for treatment of acute hepatitis C36 has shown higher response rates with starting therapy at weeks 8 or 12 versus week 20. Moreover, another study assessing the efficacy, safety and optimal duration of PEG-IFN treatment22 has shown higher response rates with the 24 weeks regimen. These studies have been used in our modelling to set Gut 2009;58:105–110. doi:10.1136/gut.2007.145516