Plasma levels and hepatic mRNA expression of transforming growth factor-beta1 in patients with fulminant hepatic failure.
OBJECTIVE
Transforming growth factor-beta1 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-beta1 in patients with fulminant hepatic failure in whom liver regeneration may be impaired.


METHODS
Plasma levels of transforming growth factor-beta1 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-beta1 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-beta1 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 beta1 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-beta1 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-beta1 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-beta1 together with a less elevated hepatocyte growth factor could be related to impaired liver regeneration in this group.
Miwa
Y
Y
Institute of Liver Studies, King's College School of Medicine and Dentistry, London, UK.
Harrison
P M
PM
Farzaneh
F
F
Langley
P G
PG
Williams
R
R
Hughes
R D
RD
D000082:Acetaminophen / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects; D015152:Blotting, Northern; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006501:Hepatic Encephalopathy / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000628:therapy; D006525:Hepatitis, Viral, Human / Q000150:complications; D017228:Hepatocyte Growth Factor / Q000097:blood; D006657:Histones / Q000032:analysis; D006801:Humans; D008099:Liver / Q000737:chemistry; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D006657:Histones; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000082:Acetaminophen; D017228:Hepatocyte Growth Factor