Refractory response to growth factors impairs liver regeneration after hepatectomy in patients with viral hepatitis.
OBJECTIVE
Liver regeneration after surgical resection is important. The present study was designed to understand the effect of background liver damage on the rate of liver tissue regeneration after hepatectomy and the mechanism of any defective regeneration.


METHODS
The subjects were 40 patients who underwent liver resection. They comprised 22 patients with chronic viral hepatitis-hepatocellular carcinoma (liver damage group) and 18 patients with hepatic metastases from colorectal cancer (normal liver group). Liver regeneration was evaluated by histopathological and immunohistochemical examination of the surgically resected tissue and by CT-scanning of the regenerated liver mass. The resected liver specimens were stained for c-met, gp-130 and nuclear factor-kappaB (NF-kappaB) proteins.


RESULTS
Liver regeneration was significantly less in the liver-damage group than in the normal-liver group. Histopathological examination showed marked inflammatory cell infiltration in the liver-damage group. Expression of c-met, but not gp-130, was significantly higher on parenchymal cells of the liver-damage group than the normal-liver group. NF-kappaB expression in parenchymal liver cells was significantly higher than in non-parenchymal cells of the normal-liver group. In the liver-damage group, liver regeneration correlated negatively with the staining intensity of NF-kappaB protein in non-parenchymal cells. These findings suggest that non-parenchymal cells are constitutively activated in the damaged liver, probably explaining the refractoriness of hepatocytes to cytokine-induced proliferation after hepatectomy, in spite of increased receptor (c-met) expression.


CONCLUSIONS
The refractory response of injured hepatocytes to cytokines may explain the impaired postoperative liver regeneration in patients with damaged liver.
Umeda
Y
Y
Department of Gastroenterological Transplant Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Iwagaki
H
H
Ozaki
M
M
Ogino
T
T
Iwamoto
T
T
Yoshida
R
R
Shinoura
S
S
Matsuda
H
H
Sadamori
H
H
Tanaka
N
N
Yagi
T
T
D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000556:secondary / Q000601:surgery*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000473:pathology; D005260:Female; D006498:Hepatectomy / Q000379:methods*; D006525:Hepatitis, Viral, Human / Q000601:surgery*; D006801:Humans; D016014:Linear Models; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary / Q000601:surgery*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D018709:Statistics, Nonparametric; D014057:Tomography, X-Ray Computed
D014408:Biomarkers, Tumor; D016328:NF-kappa B; D019859:Proto-Oncogene Proteins c-met; D051058:Oncogene Protein v-akt