Hepatitis C virus infection spontaneous clearance: Has it been underestimated?

Objectives: Hepatitis C virus (HCV) clearance rate (f_clearance) is defined as the proportion of infected persons who will spontaneously clear their infection after acute infection. We aimed to estimate f_clearance using a novel approach that avoids limitations in existing estimates, and to clarify the link between f_clearance and HCV viremic rate-the latter being the proportion of RNA positivity among those antibody positive.

Methods: A mathematical model was developed to describe HCV transmission. f_clearance was estimated by fitting the model to probability-based and nationally representative population-based data for Egypt (Egypt 2008 and Egypt 2015) and USA (NHANES A and NHANES B). Uncertainty and sensitivity analyses were conducted.

Results: f_clearance was estimated at 39.9% (95% uncertainty interval (UI): 34.3%-46.4%) and 33.5% (95% UI: 29.2%-38.3%) for Egypt 2008 and Egypt 2015 data, respectively; and at 29.6% (23.0%-37.1%) and 39.9% (31.2%-51.0%) for NHANES A and NHANES B data, respectively. f_clearance was found related to HCV viremic rate through (approximately) the formula f_clearance=1.16 (1-HCV viremic rate). HCV viremic rate was higher with higher risk of HCV exposure. Robustness of results was demonstrated in uncertainty and sensitivity analyses.

Conclusion: One-third of HCV-infected persons clear their infection spontaneously, higher than earlier estimates-the immune-system capacity to clear HCV infection may have been underestimated.