Methods for determining chronic hepatitis C infection are provided by the present invention. The methods generally involve determining the optical density of fluid samples which have tested positive for hepatitis C infection using an antibody-based assay. The optical density can then be used to determine in a predictive or probability-based manner whether the fluid sample contains chronic hepatitis C infection or whether the fluid sample merely contains antibodies to hepatitis C infection without resorting to costly molecular detection methods. Thus, the present invention permits differentiation between individuals who have cleared hepatitis C infection but still test positive in an antibody-based assay from individuals having chronic hepatitis C infection.