Plasma levels and hepatic mRNA expression of transforming growth factor-β 1 in patients with fulminant hepatic failure

Abstract

Background/Aims: Transforming growth factor-β 1 is an important cytokine involved in cell growth and inflammation which has been shown to be inhibitory to hepatic DNA synthesis. The aim of this study was to investigate the plasma levels and hepatic mRNA expression of transforming growth factor-β 1 ni patients with fulminant hepatic failure in whom liver regeneration may be impaired. Methods: Plasma levels of transforming growth factor-β 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 factor-β 1 and H3 histone, a marker for liver proliferation, was performed in liver tissue of 14 fulminant hepatic failure patients. Results: The plasma levels of total transforming growth factor-β 1 in fulminant hepatic failure patients on admission (median 38.8 ng/ml, range 8.4–108 ng/ml) were significantly higher than those in control subjects (23.0 ng/ml, 8.5–34.9 ng/ml, p<0.001). Significantly higher levels 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 overdose (37.1 ng/ml, 8.4–72.5 ng/ml, n=47). In contrast, the plasma levels of free transforming growth factor β 1 were greater in paracetamol overdose (623 pg/ml, 46.7–1241 pg/ml, n=21) than in non-A, non-B hepatitis (131 pg/ml, 77.2–254 pg/ml, n=9), with both being higher than control (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 patients 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-β 1 in paracetamol-overdose patients ( n=8, p<0.05), but not in patients with non-A non-B hepatitis ( n=6), compared to controls ( n=4). Conclusions: The increased circulating plasma TGF-β 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 transforming growth factor-β 1 together with a less elevated hepatocyte growth factor could be related to impaired liver regeneration in this group.