Tumour necrosis factor alpha and cellular proliferation in primary biliary cirrhosis

1) To evaluate serum levels and tissue expression of Tumour necrosis factor alpha in primary biliary cirrhosis: 2) to correlate serum tumour necrosis factor alpha levels and cellular proliferation with the severity and prognosis of liver disease.

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 measured by EIA (Innogenetics, Antwerp, Belgium). Tissue tumour necrosis factor alpha and Ki-67 were tested by indirect immunoperoxidase staining on liver sections.

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 stage III and 22.8 +/- 8.7 in stage IV, p < 0.036). A positive correlation was also found between tumour necrosis factor alpha serum levels and the Mayo score (p < 0.05). A weak and sporadic expression of tumour necrosis factor alpha was observed in the inflammatory infiltrate around the bile ducts. Tissue Ki-67 (expressed as the labelling index in the hepatocellular nuclei) was evaluated in all stages of the disease (1.09 +/- 0.6% in stage I, 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 Mayo score was observed (p < 0.0005).

1) tumour necrosis factor alpha production seems related to the severity and the prognosis of primary biliary cirrhosis; 2) liver mononuclear cells in the inflammatory infiltrate do not seem to be the major site of tumour necrosis factor alpha release; 3) cellular proliferation is correlated with the severity of liver disease.