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

• Published in: Digestive and liver disease Vol. 53; no. 7; pp. 860 - 865
• Main Authors: de Faria, Atila Granados Afonso, Chaves, Fernanda Correa, Ferraz, Maria Lucia Gomes, Andrade, Luis Eduardo Coelho
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.07.2021
• Subjects: Adult; Alanine Transaminase - blood; Biomarkers - blood; Case-Control Studies; Complement Activation; Complement C2 - analysis; Complement system; Cryoglobulin; Cryoglobulinemia - blood; Cryoglobulinemia - virology; Cryoglobulins - analysis; Female; Genotype; HCV; Hepacivirus - genetics; Hepatitis; Hepatitis C - blood; Hepatitis C - virology; Humans; Liver Function Tests; Male; Middle Aged; Risk Factors; RNA, Viral - blood; Viral Load; Cryoglobulin; FH; AST; ECA; IRN; ALT; Hepatitis; ANA; MBL; ULN; C2h; APRI; Complement system; HCV; FB; CH100
• ISSN: 1590-8658; 1878-3562; 1878-3562
• DOI: 10.1016/j.dld.2020.12.124

Some HCV patients present low/non-detected C2 hemolytic activity (C2h) without apparent consumption of other Complement components (selective low/non-detected C2h). Characterization of the immunologic/clinical basis of this phenomenon. C2h, HCV-viral load, cryoglobulinemia and Complement components were determined in 726 HCV patients, with sequential C2h determination in 189 patients. 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. 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.