Serum complement in chronic liver disease

Abstract

SUMMARY Total serum haemolytic complement activity (CH50) and the serum concentrations of both the third and fourth components ofthe complement system (C3 and C4) have been measured in 29 control subjects, 92 patients with chronic hepatocellular disease, and eight patients with large duct biliary tract obstruction. The mean C4 concentration was reduced in all types of chronic liver disease studied. However, the mean CH50 and C3 values were increased in compensated primary biliary cirrhosis, were relatively normal in non-cirrhotic chronic active hepatitis, and were decreased in cryptogenic cirrhosis, particularly when ascites was present. There was a significant correlation between CH50 and C3 in patients with chronic liver disease but no correlation between CH5o and C4 or between C3 and C4. Raised values for CH50 and C3 in primary biliary cirrhosis may be due at least in part to concomitant cholestasis since these values tend to be raised in patients with large duct biliary tract obstruction. Although primary biliary cirrhosis, chronic active hepatitis, and cryptogenic cirrhosis are considered to be part of a spectrum of chronic liver disease associated with disturbed immunity, the results of this study emphasize that there are clearly definable differences between these diseases in terms of the pattern of changes in serum complement.Although some types of chronic liver disease, such as chronic active hepatitis, primary biliary cirrhosis, and cryptogenic cirrhosis are usually associated with evidence of disturbed immunity, so far no immune mechanism has been demonstrated to be of fundamental importance in the pathogenesis of these diseases. One well established cause of cell lysis and death involves the complement system, classically activated by antigen-antibody interaction on a cell surface (Rapp and Borsos, 1970). If this immune process is responsible for liver cell injury in patients with chronic liver disease, there may be associated changes in serum complement. However, changes in the complement system may also arise as a consequence of the disease process itself.It has previously been shown that patients with chronic liver disease tend to have a reduced total serum complement haemolytic activity (Goldner, 1929;Jordan, 1953;Asherson, 1960;Townes, 1967; Inai, Fujikawa, Naguki, Takahashi, Ozono, and Ishida, 1967;Farini, Gambari, Fagiolo et al, 1970;Pagaltsos, Smith, Eddleston, and Williams, 1971; De Meo and Anderson, 1972;Torisu, Yokoyama, Kohler, Durst, Martineau, Schroter, Amemiya, Groth, and Starzl, 1972) and a reduced serum concentration of the third component of comple-

Receptor Specific Clearance by the Reticuloendothelial System in Chronic Liver Diseases

“…In patients with PBC there was no depression in serum complement. Indeed, in several patients C3 levels in serum were increased, an observation in agreement with other data (29). Except for one patient with CH, not shown in the figure, in whom the total hemolytic complement was 0 CH50 U and hemolytically active C4 was less than 1,000 hemolytic U, levels of complement were not decreased in any patient group.…”

Streptococcus salivarius bacteremia and spontaneous bacterial peritonitis in liver transplantation candidates

“…An episode of S salivarius SBP was defined either as bacteremia together with positive ascitic fluid culture or as bacteremia together with an ascitic fluid absolute polymorphonuclear leukocyte count of 250 cells/mm 3 or more. Infections were considered community acquired when diagnosed within the first 48 hours of hospitalization and hospital acquired when diagnosed after 48 hours of hospitalization.…”

“…1,2 Proposed mechanisms for increased risk of infection are changes in humoral immunity with a decreased synthesis in the complement system, 3 a decrease in the phagocytosis capability of the hepatic reticuloendothelial system, 4 an alteration in the function of neutrophils, 5,6 and a reduction in opsonic activity of ascitic fluid. 7 In addition, rupture of natural barriers induced by invasive diagnostic or therapeutic procedures may be involved in the pathogenesis of infections.…”

Pathophysiology of renal disease associated with liver disorders: Implications for liver transplantation. Part I

“…[153][154][155][156] Cirrhosis is associated with decreased complement levels (C3, C4, and total complement) caused by impaired hepatic production, as well as enhanced consumption. [157][158][159][160] Consumption is mediated through both the alternative and classical complement pathways. Endotoxin (microbial cell membrane) stimulates the alternative complement pathway.…”