Background/Purpose – Hepatitis C virus (HCV) causes immunologic disorders (vasculitis, myositis, arthritis) and high frequency of autoantibodies and mixed cryoglobulinemia (CRYO). Recently, we observed that some HCV patients present absent serum C2 hemolytic activity without consumption of other components of the Complement System (CS). Liver enzyme (AST/ALT) serum levels were registered as the times the upper limit of normal (ULN). This study characterizes this phenomenon in a large series of consecutive HCV patients.

Methods – 1021 samples from 716 consecutive HCV patients were analyzed for CS parameters: functional assessment of C2 (radial immune-hemolysis); C2, C3 and C4 protein concentration (immune-precipitation). Clinical and laboratory data were obtained from a structured medical form.

Results -Samples were classified into three groups according to C2 hemolytic activity: 1) Absent activity (n=154; 15.1%); 2) Decreased activity (n=154; 15.1%); 3) Normal activity (n=713; 69.8%). Most samples with decreased/absent C2 activity had decreased serum C2 protein concentration. Serum C3 and C4 was normal in 89 (82%) and 82 (72%), respectively, of samples with absent C2 activity. Analysis of multiple sequential samples from 192 patients showed that the selective decrease in C2 activity is a transient phenomenon with variable duration in time. Patients with absent C2 activity had higher serum liver enzymes (AST/ALT) (2,46±1,25 ULN and 2,29±2,15 ULN) and lower serum albumin (4,0±0,6mg/dL) than those with normal C2 activity (AST 1.46±1,25 ULN p<0.001; ALT 1.62±1.47 ULN; p=0.03; albumin 4,3±0,5; p=0.01). Samples with absent C2 activity had higher frequency of CRYO (13%) than those with normal C2 activity (0.8%) (p<0.001). In vitro exposure of normal to CRYO induced selective decrease in C2 activity in a dose-dependent manner. C2 activity status was not associated with other clinical and laboratory parameters.

Conclusion – Selective decreased C2 activity is transiently observed in 30% of HCV patients. This phenomenon was associated with liver biochemical abnormalities and CRYO. Further studies are warranted to define the role of these and other yet unknown factors on selective C2 deficiency in HCV patients.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/selective-consumption-of-c2-component-in-hcv-patients/