Soluble CD163, a Macrophage Activation Marker, Is Independently Associated With Fibrosis in Patients With Chronic Viral Hepatitis B and C

Macrophages are involved in inflammation and liver fibrosis and soluble (s)CD163 is a specific marker of activated macrophages. We investigated associations between sCD163 and biochemical and histological parameters of inflammatory activity and fibrosis in 551 patients with chronic hepatitis C virus (HCV) and 203 patients with chronic hepatitis B virus (HBV) before antiviral treatment. Scheuer histological scores of activity and fibrosis were obtained. Clinical, biochemical, and metabolic parameters were recorded. We measured sCD163 by enzyme-linked immunosorbent assay (ELISA). Soluble CD163 was higher in patients with HCV compared to HBV (3.6 [interquartile range (IQR) 2.5-5.4] versus 2.4 [IQR 1.8-3.6] mg/L, P < 0.001). sCD163 was associated with fibrosis stages for both HCV (odds ratio [OR] 1.49, 95% confidence interval [CI]: 1.38-1.61) and HBV (OR 1.32, 95% CI: 1.17-1.49) patients, with highest levels in patients with advanced fibrosis and cirrhosis. sCD163 was a marker of fibrosis independent of other biochemical parameters and known risk factors. We created two novel sCD163-based fibrosis scores, CD163-HCV-FS and CD163-HBV-FS, which showed areas under the receiver operating characteristics curve (AUROC) of 0.79 (95% CI: 0.74-0.83) and 0.71 (95% CI: 0.62-0.79), respectively, for significant fibrosis. Compared to existing fibrosis scores, CD163-HCV-FS was significantly superior to the aspartate aminotransferase (AST) to platelet ratio index (APRI) for all fibrosis stages and to FIB-4 for significant fibrosis, but CD163-HBV-FS was not. Conclusion: sCD163 levels are increased in patients with chronic viral hepatitis, reflecting macrophage activation. Increased sCD163 is associated with the severity of disease and predicts fibrosis. A sCD163-based fibrosis score, CD163-HCV-FS, is superior to APRI and FIB-4 for the diagnosis of significant fibrosis in patients with HCV infection.