Tumour necrosis factor alpha and cellular proliferation in primary biliarycirrhosis

Aims, II To evaluate serum levels and tissue expression of Tumour necrosis factor alpha in primary biliary cirrhosis; 2) to correlate serum tumour nec rosis factor alpha levels and cellular proliferation with the severity and prognosis of liver disease. Methods. Twenty-nine primary biliary cirrhosis patients (6 stage I, 8 II, 8 III and 7 IV) entered the study Serum tumour necrosis factor alpha was mea sured by EIA (Innogenetics, Antwerp, Belgium). Tissue tumour necrosis facto r alpha and Ki-67 were tested by indirect immunoperoxidase staining on live r sections. Results. Serum tumour necrosis factor alpha increased with the severity of histological stage (from 10.8 +/- 11 pg/ml in stage II to 17.1 +/- 10 in st age in and 22.8 +/- 8.7 in stage IV, p<0.036). A positive correlation,cas a lso found between tumour necrosis factor alpha serum levels and the Mayo sc ore (p<0.05). A weak and sporadic expression of tumour necrosis factor alph a was observed in the inflammatory infiltrate around the bile ducts. Tissue Ki-67 (expressed as the labelling index in the hepatocellular nuclei) was elevated in all stages of the disease (1.09 +/- 0.6% in stage 1, 1.14 +/- 0 .6% in stage II, 2.11 +/- 1.9% in stage III, and 2.67 +/- 2.8% in stage IV; the labelling index was significantly lower in early stages (I/II) than in late stages (III/IV), p<0.05. A strong correlation between Ki-67 and the M ayo scare was observed (p<0.0005). Conclusions. 1) tumour necrosis factor alpha production seems related to th e severity and the prognosis of primary biliary cirrhosis; 2) liver mononuc lear cells in the inflammatory infiltrate do nor seem to be the major site of tumour necrosis factor alpha release; 3) cellular proliferation is corre lated with the severity of liver disease.