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The role of ascitic fluid collagen in the pathogenesis of the coagulopathy that follows peritoneovenous shunting was examined. Collagen was partially purified from ascitic fluid and infused into rabbits. All animals developed changes in their haemostatic profile consistent with intravascular coagulation. Aspirin therapy, for five days before the collagen infusion, prevented these changes. Seven patients undergoing a total of eight peritoneovenous shunts for intractable ascites received antiplatelet therapy (aspirin and dipyridamole) in the immediate pre- and postoperative period. After six shunts no thrombocytopenia or prolongation of clotting times developed to suggest decompensated consumptive coagulopathy. Complicating factors may have contributed to the deterioration in haemostasis in the other two patients. There was no early shunt occlusion. The results support the hypothesis that ascitic fluid collagen is important in the pathogenesis of intravascular coagulation postascitic fluid infusion and indicate that antiplatelet drugs may be of value in preventing this complication. [ABSTRACT FROM PUBLISHER]

The effect of alcoholic patient sera on lymphocyte transformation was studied using mitogen-induced uptake of H-thymidine to measure blastogenesis. With pokeweed mitogen as the stimulus, transformation of normal lymphocytes in sera of alcoholics with either normal or fatty livers was not significantly different from that obtained in pooled human serum (PHS). However, in sera of patients with either alcoholic hepatitis or inactive cirrhosis mean transformation was significantly reduced (P <0·001, <0·02 respectively). With phytohaemagglutinin-P or concanavalin A as mitogens, suppression of transformation was not as marked but followed the same pattern. A significant negative correlation was observed between the magnitude of transformation and serum bilirubin and aspartate aminotransferase levels. An intra-patient comparison of the effects on transformation of normal lymphocytes by simultaneously collected peripheral and portal venous sera, and of peripheral sera obtained before and after portasystemic shunt surgery, indicated that the factor(s) responsible did not originate in the splanchnic circulation nor did it accumulate in the serum because of failed hepatic clearance. By performing transformation experiments in the presence of inhibitory patient sera diluted with PHS it was possible to show that these sera caused true inhibition of transformation rather than suppression due to failure to sustain cell culture because of nutritional deficiencies. Inhibitory sera did not contain high levels of the enzyme thymidine phosphorylase and did not significantly inhibit binding of I-labelled mitogens to the lymphocyte surface. These findings indicate that the inhibitory effect of sera from alcoholics is of potential importance, that the effect increases with the degree of heptocyte damage, and that it is unrelated to the nonhepatic metabolic affects of chronic alcoholism. [ABSTRACT FROM PUBLISHER]

The effect of liver disease on glucagon metabolism was examined in nine patients with chronic liver disease who were studied both before and after the creation of a surgical portasystemic shunt. Hepatocellular function did not deteriorate after shunt surgery. However, hepatic perfusion with splanchnic venous blood, as determined by scintisplenoportography, decreased after shunt surgery in six subjects but appeared unaltered in three. Basal plasma immunoreactive glucagon (IRG) levels in the pre-shunt cirrhotic group were significantly greater ( <0·005) than in control subjects and further increased ( <0·05) after shunt surgery. Moreover, the increase in basal IRG after shunt was evident only in patients in whom portasystemic shunting was demonstrably increased by surgery. Despite the higher basal IRG levels postoperatively, shunt surgery in the cirrhotics did not alter basal glucose and insulin levels or the glucose and insulin response to a glucose or protein load. Circulating IRG was heterogeneous in the pre-shunt cirrhotic patients: the 9000 molecular weight fraction comprised 27±4%, the 3500 mol. wt. fraction 71±4%, and the > 40 000 mol. wt. fraction was minimal. After shunt surgery, the relative proportion of the 9000 mol. wt. fraction of IRG (13±3%) decreased significantly ( <0·05) and this fall was associated with a corresponding increase in the 3,500 mol. wt. fraction (84±4%). It is concluded that, in cirrhosis, hyperglucagonaemia is: (1) dependent on the degree of portasystemic shunting rather than impaired hepatocellular function; (2) predominantly due to increased circulating 3500 molecular weight glucagon; and (3) not a major factor in the pathogenesis of carbohydrate intolerance in liver disease. [ABSTRACT FROM PUBLISHER]

Both the humoral and cellular immune response to haemocyanin was measured in normal subjects and patients with liver disease including primary biliary cirrhosis, other forms of cholestasis, and cryptogenic cirrhosis. Significant differences in antibody titre were found 2 weeks after immunization being highest in normal subjects, less in cryptogenic cirrhosis and least in primary biliary cirrhosis. The incidence of positive skin tests, indicating the development of delayed hypersensitivity to haemocyanin, was significantly less in patients with primary biliary cirrhosis and cryptogenic cirrhosis than in those with cholestasis or the normal subjects. It is suggested that the poor antibody response seen in primary biliary cirrhosis, could be related to impaired T cell function and hence lack of the T and B cell co-operation necessary for antibody formation to some antigens. The presence of delayed hypersensitivity to haemocyanin as measured by the skin test was compared to other tests of delayed hypersensitivity including the tuberculin skin test, DNCB sensitization and PHA-stimulated in vitro lymphocyte transformation. Of twenty patients with primary biliary cirrhosis the results of all four tests correlated in nine but did not agree in the remaining eleven patients. These results emphasize the importance of using a number of indices when assessing the degree of energy of any one patient. [ABSTRACT FROM AUTHOR]

Sera from 134 HAA positive patients have been studied for the presence of a variety of autoantibodies. The patients were divided into groups dependent on the clinicopathological severity of the associated liver disease. Both smooth muscle antibody and rheumatoid factor were found in all groups of patients. However, their incidence and titre was higher in the groups of patients who had clinical and pathological evidence of the more active liver cell damage. As autoantibodies in viral infections may be an index of the presence of cell mediated immunity to the causative infective agent these results could support the hypothesis that cell mediated immunity is important in the pathogenesis of liver cell damage in HAA positive patients. [ABSTRACT FROM AUTHOR]

Serum immunoglobulin G, A, and M and serum antinuclear, mitochondrial, and smooth muscle antibody have been measured in 223 patients with hepatitis-associated antigen (HAA)-positive and -negative acute and chronic liver disease. In patients with acute hepatitis, chronic persistent hepatitis, and primary liver cell carcinoma, these indices failed to show any significant differences. However, in the group with chronic aggressive hepatitis the patients who were HAA negative had significantly higher levels of serum IgG, much higher titres of smooth muscle antibody, and often antinuclear and mitochondrial antibodies which were not found in the HAA-positive patients from this group. This suggests that different pathogenic mechanisms may be operative in HAA-positive and -negative chronic aggressive hepatitis. [ABSTRACT FROM PUBLISHER]

The aim of this study was to determine the importance of plasma inhibitory factors in producing the impaired phytohaemagglutinin (PHA)-induced lymphocyte transformation that is seen in some patients with primary biliary cirrhosis. Twenty-six normal subjects and 12 patients with primary biliary cirrhosis were studied. The lymphocytes from each subject were cultured in the presence of autologous plasma and also in the presence of homologous plasma from a normal subject or from a patient with primary biliary cirrhosis. The results confirm that a proportion of patients with primary biliary cirrhosis are anergic and that the impaired lymphocyte transformation to PHA can be partially accounted for by the presence of inhibitory factors in the plasma. However, these factors are unlikely to account completely for the impaired transformation, it being probable that there are also abnormalities of the T lymphocytes themselves. [ABSTRACT FROM PUBLISHER]

Serum C (β/β) has been measured in normal individuals and the range found is in agreement with findings of other authors (85-370 mg/100 ml). In 18 patients with acute hepatitis and massive necrosis serum C was consistently reduced to below 50% of normal. In other patients with acute hepatitis the serum C concentration was normal. In the majority of the 150 patients with chronic liver disease serum C concentration was normal. However, 10 patients (six with active chronic hepatitis, four with cryptogenic cirrhosis) had hypocomplementaemia. The reason for the depression is not clear but could reflect either decreased synthesis or increased consumption, or a combination of the two. [ABSTRACT FROM PUBLISHER]