Correlation between hepatic morphology and immunoglobulins and antibodies to Escherichia coli in cirrhosis.

Abstract

SUMMARY Increased antibody production and hypergammaglobulinaemia in cirrhosis are probably to a large extent due to decreased hepatic extraction of antigens. The decreased extraction is presumably related to changed microcirculation caused by damaged anatomical structure of the liver. It is therefore to be expected that immunoglobulin and antibody levels in serum in cirrhotic patients are related to the degree of certain morphological changes of the liver. This hypothesis has been tested. In 50 patients with cirrhosis, 28 alcoholics and 22 non-alcoholics, the degree of architectural destruction, the degree of fibrosis, the degree of fatty infiltration, and the degree of 'activity' were compared with immunoglobulins G, A, and M and E. coli 0 antibody levels. The comparison was carried out within each of the aetiological groups. Identical relationships were found in both groups. Patients with completely destroyed lobular architecture had higher levels of E. coli 0 antibodies than patients with partly destroyed architecture. Patients with severe fibrosis had higher IgA and E. coli 0 antibody levels than patients with moderate or slight fibrosis. Patients with moderate and severe steatosis and patients with no or slight steatosis had the same immunoglobulin and E. coli O antibody levels. Patients with active cirrhosis had higher IgG levels than patients with inactive cirrhosis. When architectural destruction and fibrosis were combined significantly higher IgG, IgA, IgM, and E. coli antibodies were found in the group with the most severe changes. These findings support the hypothesis that immunoglobulin and antibody levels are related to the degree of morphological changes in the liver-namely, destruction of lobular architecture, fibrosis, and 'activity'.

Endotoxemia in a Series of 104 Patients with Chronic Liver Diseases: Prevalence and Significance

“…In the CAH group, however, endotoxemia was correlated with raised serum y-globulin levels, supporting the hypothesis [9,18] that the high immunotiters observed in chronic liver diseases may be accounted for by an impaired clearance of bacterial antigens by the liver. Moreover, in this group the cases with endotoxemia showed a high degree of portal and periportal inflammation with bridging more frequently than those without endotoxemia.…”

Hepatitis Bs antibody in alcoholic cirrhosis.

“…The gut antigens may avoid sequestration in the liver because of direct Kupffer cell damage or because they bypass the Kupffer cell filter by way of collateral circulation. Antibodies to Escherichia coli in patients with cirrhosis correlated well with the degree of architectural destruction and fibrosis on liver biopsy (Prytz et al, 1977) but were not raised in the setting of portocaval shunting and inactive cirrhosis (Simjee et al, 1975). Therefore, hepatic Kupffer cell damage appears to be the important factor in the increased response to gut antigens.…”

Development of Hodgkin’s disease in the course of liver cirrhosis and impaired monocyte function

“…However, several mechanisms explaining the development of lymphoma in the course of liver disease have been offered: prolonged antigenic stimulation (Prytz et al, 1977), immunosuppressive therapy (Viteri et al, 1976;Harris, 1976) and presence of hepatitis B surface antigen (Wands et al, 1975).…”

“…Prolonged antigenic stimulation has been suggested to be operative in chronic liver disease, resulting most probably from the decreased antigenic elimination by the diseased liver with impaired reticuloendothelial function (Prytz et al, 1977). The permanent antigenic stimulation maintains a proliferation of the lymphoid system which could deviate towards malignancy (Editorial, 1970).…”

“…The activity of Kupffer cells, which belong to this system, has already been partially studied in the diseased liver, and was found impaired (Prytz et al, 1977;Bjorneboe, Prytz and Orskov, 1972). Sherlock (1977) has stated that there were no data available that monocyte function is impaired in cirrhosis ofliver, but that these cells are functionally incapacitated by the by-pass of portal blood by way ofthe portocaval anastomoses.…”