Impaired tuftsin activity in cirrhosis: relationship with splenic function and clinical outcome

Abstract

Background: Cirrhotic patients show increased susceptibility to bacterial infections. It is not known whether tuftsin deficiency, which is associated with an increased incidence of infections in many disease states, is present in cirrhosis. Our aims were to determine whether tuftsin activity is deficient in cirrhosis and if so, whether this deficiency is related to splenic function, contributes to altered neutrophil granulocyte function, or influences the occurrence of bacterial infections and patient survival. Methods: Tuftsin activity and splenic function were assessed in 31 patients with liver cirrhosis and 31 healthy subjects. The phagocytic activity of neutrophil granulocytes from 23 patients was tested in vitro with addition of both autologous and pooled sera from healthy subjects. In 10 patients and eight controls it was also tested with addition of synthetic tuftsin. Patients were followed up until death or liver transplantation. Results: Patients had reduced tuftsin activity (median 8% (range 3-24.5)) compared with controls (17% (11.5-37)) (p<0.001) and a higher pitted red cell count (p<0.001). Tuftsin activity was correlated with pitted cell count (p=0.02) and the Child-Pugh score (p=0.002). Nineteen of 23 patients showed deficient phagocytic activity of neutrophil granulocytes, which was correlated with tuftsin activity (p<0.001), improved in all cases but one with addition of serum from healthy subjects, and normalised with addition of synthetic tuftsin. Reduced tuftsin activity did not influence patient survival but was associated with a higher incidence of bacterial infections (p=0.029). Comment: Tuftsin activity was reduced in cirrhosis, and contributed to impaired phagocytic activity of neutrophil granulocytes. Such an abnormality appears to be related to impaired splenic function and severity of cirrhosis, and probably favours the occurrence of bacterial infections.

Bacterial translocation (BT) in cirrhosis

“…Impaired tuftsin activity, known to modulate biological activities of phagocytic cells, is reduced in patients with cirrhosis and is associated with a higher incidence of bacterial infections. 75 Reduced complement levels as well as defects in Fcy-receptors on mononuclear cells may contribute to decreased opsonic activity. [76][77][78] In patients with cirrhosis, low ascites complement levels correlate with decreased opsonic activity, decreased bactericidal activity and increased risk for SBP.…”

Frequency of toxoplasmosis in patients with cirrhosis

“…Toxoplasmosis may rarely cause various liver pathologies due to granulomatose hepatitis in patients with normal immune systems [1,[5][6][7][8] . Patients with cirrhosis of the liver demonstrate various cellular and humoral immunity disorders [9][10][11][12] . For this reason, it may be thought that toxoplasmosis may lead to more frequent and more severe diseases in patients with cirrhosis and change the course of the disease.…”

Effect of Liver Transplantation on Tuftsin Activity and Phagocytic Activity of Neutrophil Granulocytes in Patients with Liver Cirrhosis

“…We previously found that TA deficiency was related to the degree of severity of cirrhosis and spleen dysfunction [10]. Conceivably, OLT improves TA by relieving both liver insufficiency and portal hypertension [13, 14], the latter being a major cause of splenic dysfunction in cirrhosis.…”

“…Nine cirrhotic patients who had been enrolled in our previous study [10] and thereafter underwent OLT because of advanced liver disease (7 cases), recurrent variceal bleeding (1 case) and hepatocellular carcinoma (1 case) took part in the present investigation. Three were males and 6 females; their median age was 55 years (range: 35–62).…”

“…We have recently demonstrated that tuftsin activity (TA) is also reduced in patients with cirrhosis [10]. In this context, its deficiency, which is correlated with both the severity of cirrhosis and impairment of splenic function, contributes to impaired phagocytic activity (PA) of neutrophil granulocytes and favours the occurrence of bacterial infections.…”