PLASMA-LEVELS AND HEPATIC MESSENGER-RNA EXPRESSION OF TRANSFORMING GROWTH FACTOR-BETA(1) IN PATIENTS WITH FULMINANT HEPATIC-FAILURE

Background/Aims: Transforming growth factor(beta)(1) is an important c ytokine involved in cell growth and inflammation which has been shown to be inhibitory to hepatic DNA synthesis. The aim of this study was t o investigate the plasma levels and hepatic mRNA expression of transfo rming growth factor-beta(1) in patients with fulminant hepatic failure in whom liver regeneration may be impaired. Methods: Plasma levels of transforming growth factor-beta(1) and human hepatocyte growth factor were measured in 57 fulminant hepatic failure patients and 20 healthy volunteers by ELISA. Northern blot analysis of transforming growth fa ctor-beta(1) and H3 histone, a marker for liver proliferation, was per formed in liver tissue of 14 fulminant hepatic failure patients. Resul ts: The plasma levels of total transforming growth factor-beta(1) in f ulminant hepatic failure patients can admission (median 38.8 ng/ml, ra nge 8.4-108 ng/ml) were significantly higher than those in control sub jects (23.0 ng/ml, 8.5-34.9 ng/ml, p<0.001). Significantly higher leve ls were observed in non-A, non-B hepatitis patients (57.9 ng/ml, 38.8- 108 ng/ml, n=10, p<0.001) compared to patients with paracetamol overdo se (37.1 ng/ml, 8.4-72.5 ng/ml, n=47). In contrast, the plasma levels of free transforming growth factor beta(1) were greater in paracetamol overdose (623 pg/ml, 46.7-1241 pg/ml, n=21) than in non-A, non-B hepa titis (131 pg/ml, 77.2-254 pg/ml, n=9), with both being higher than co ntrol (72.3 pg/ml, 28.7-108, n=7, p<0.001). The plasma levels of human hepatocyte growth factor in patients with paracetamol overdose (7.04 ng/ml, 1.00-62.4 ng/ml) were significantly higher than those in patien ts with non-A, non-B hepatitis (4.48 ng/ml, 0.74-9.10 ng/ml, p<0.05). Northern blots showed increased mRNA expression of transforming growth factor-beta(1) in paracetamol-overdose patients (n=8, p<0.85), but no t in patients with non-A non-B hepatitis (n=6), compared to controls ( n=4). Conclusions: The increased circulating plasma TGF-beta(1) in FHF may be part of the tissue repair process in fulminant hepatic failure . In patients with non-A, non-B hepatitis, the increased total transfo rming growth factor-beta(1), together with a less elevated hepatocyte growth factor could be related to impaired liver regeneration in this group.