Significance of hyperglobulinemia in severe chronic liver diseases - with special reference to the correlation between serum globulin/IgG level and ICG clearance

Background/Aims: Although hyperglobulinemia is frequently detected in severe chronic liver diseases (CLD) such as liver cirrhosis (LC), the mechanism for this is still uncertain. Hyperglobulinemia may represent a functional aspect of the liver. Methodology: The correlation between serum globulin (GLB) level and each of various liver function tests including the indocyanine green (ICG) retention rate at 15min (ICGR(15)) was studied using 146 patients with liver dysfunction. The correlations among GLB, IgG and ICGR(15) were also studied in other 32 patients with LC, in whom the glycosylation pattern of IgG was determined by enzyme-linked immunosorbent assay to detect terminal galactose (Gal) and neuraminic acid (NA) using biotinylated lectins. Results: GLB level was predominantly correlated with ICGR(15) (r=0.449) among various liver function tests in 146 patients with liver dysfunction. In the 32 patients with LC, strong positive correlations between GLB and IgG (r=0.875), between GLB and ICGR(15) (r=0.435), and between IgG and ICGR(15) (r=0.557) were evident. The glycosylation pattern of IgG showed that the proportions of both Gal and NA were inversely correlated with serum IgG levels (r=-0.516 and -0.390, respectively) in these patients. Significant decreases of the proportions were found in patients with IgG elevation (> 20g/L, n=13). Conclusions: The correlation between GLB and ICGR(15) suggested that hyperglobulinemia is related to a common dysfunction estimated by ICG clearance, which represents mainly the liver's blood flow and removal capacity. The removal of immunoglobulins by the liver may be impaired in patients with severe liver dysfunction because the liver is a major catabolic site for immunoglobulins. The glycation pattern suggested that the proportions of asialo IgG and agalactosyl IgG were increased in the LC patients with IgG elevation possibly by deficient receptor-mediated removal in the liver. Although further investigations will be needed, hyperglobulinemia could be predictive for a certain impaired hepatic function estimated by ICG clearance in severe CLD such as LC.