Selective decrease in complement C2 hemolytic activity is a sensitive marker for cryoglobulinemia and active disease in hepatitis C patients.

Background: Some HCV patients present low/non-detected C2 hemolytic activity (C2h) without apparent consumption of other Complement components (selective low/non-detected C2h).

Aim: Characterization of the immunologic/clinical basis of this phenomenon.

Methods: C2h, HCV-viral load, cryoglobulinemia and Complement components were determined in 726 HCV patients, with sequential C2h determination in 189 patients.

Results: C2h was non-detected in 15.9%, low in 16.9% and normal in 67.2% subjects and showed temporal oscillation in 30.7% of patients. Samples with selective non-detected C2h presented lower C3/C4 than those with normal C2h, but still within the normal C3/C4 range. Selective non-detected C2h was associated with higher aspartate aminotransferase (AST) (p<0.001), alanine transferase (ALT) (p = 0.03) and APRI (Aspartate aminotransferase-to-Platelet Ratio Index) (p<0.001), lower serum albumin (p = 0.01) and platelet count (p = 0.012), more individuals at pre-treatment stage, with detectable HCV-RNA p<0.001), cryoglobulinemia (p<0.001) and with HCV genotype 3 (p = 0.003). Elevated ALT, HCV genotype 3, active disease and viral load were independent predictors of low/non-detected C2h. In vitro exposure of normal serum to exogenous HCV cryoglobulins caused dose-dependent decrease in C2h.

Conclusions: Selective C2h decrease is a sensitive marker of Complement activation in HCV patients and is associated with cryoglobulinemia, active disease, elevated ALT, higher viral load, and HCV genotype 3.