[11] Conversely, the U.S. Preventive Services Task Force (USPSTF) issued a draft Recommendation Statement in November 2012 that gave such birth-cohort screening only a grade C recommendation.[12] Grade C is defined as clinicians may provide this service to selected patients depending on individual circumstances; however, for most individuals without signs or symptoms there is likely to be only a small benefit from this service. One issue that likely led to the unexpected Inhibitor Library chemical structure grade C recommendation by the USPSTF was the scant evidence that birth cohort screening would lead to decreased all-cause mortality—the

ultimate clinical outcome. The present work by van der Meer et al. further contributes to the body of evidence that SVR achieved from HCV antiviral treatment is associated with significant reduced all-cause mortality. These data, however, face the limitation of all such observational outcome data that patients cannot be randomized to SVR versus no SVR. Thus, SVR may be a marker for some other unmeasured residual confounder responsible for the lower all-cause mortality. Given the extent of the effect demonstrated

by van der Meer et al.—the risk of all-cause mortality was almost 4-fold lower in patients with SVR compared with DNA Damage inhibitor patients without SVR—however, it is difficult to envision what such a confounder could be. Although extrapolating these data as support for expanded birth cohort testing is enticing, one must also consider the issue of how the patients followed in the present study were initially identified as being HCV-positive and whether that can be extrapolated to other populations. Given the time of first antiviral therapy (1990-2003), it is likely that patients were identified through HCV testing prompted by high-risk behavior, symptoms, or laboratory abnormalities. Hence, it is conceivable that the observed reduction in all-cause mortality would not have been as pronounced in a

cohort identified through other criteria, such as birth MCE cohort, where no specific clinical indicator prompted HCV testing. The population reported on by Van der Meer et al. may represent a different population than that which would have been identified by broad-based birth cohort screening in terms of risk of HCV disease progression and necessity of antiviral therapy. Nevertheless, the well-designed, long-term follow-up study by van der Meer et al. has several key strengths that provide strong evidence on the association between virologic and clinical outcomes and, in particular, all-cause mortality. With strengths such as a median follow-up duration of 8.