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Published on: February 19, 2019
Detection of serum and intrahepatic human hepatocyte growth factor in patients with type C liver diseases
H Yamagami1, M Moriyama, N Tanaka
1Third Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Insights
Hepatocyte growth factor (HGF) serum levels correlate with liver disease severity in Hepatitis C patients. Elevated HGF indicates significant inflammation, fibrosis, and potentially higher cancer risk.
Area of Science:
- Hepatology
- Biochemistry
- Oncology
Background:
- Hepatitis C virus (HCV) infection leads to significant liver damage, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
- Hepatocyte growth factor (HGF) is a key regulator of cell growth, proliferation, and tissue repair.
- Understanding HGF's role in HCV pathogenesis is crucial for disease management and therapeutic development.
Purpose of the Study:
- To determine serum and intrahepatic hepatocyte growth factor (HGF) levels in patients with various stages of Hepatitis C.
- To assess the relationship between HGF levels and histological liver findings, including inflammation and fibrosis.
- To evaluate HGF expression in relation to hepatocellular carcinoma (HCC) development in HCV patients.
Main Methods:
- Serum and liver tissue samples were collected from 108 patients with chronic hepatitis C (CH), 70 with liver cirrhosis C (LC), 38 with hepatocellular carcinoma (HCC), and 20 with acute hepatitis (AH).
- Normal controls (n=20) were included for comparison.
- Serum HGF levels were quantified using enzyme-linked immunosorbent assay (ELISA).
- Intrahepatic HGF expression was analyzed via immunoperoxidase staining using monoclonal HGF antibody.
Main Results:
- Serum HGF levels were highest in acute hepatitis (AH) patients and tended to be higher in liver cirrhosis (LC) and hepatocellular carcinoma (HCC) patients compared to chronic hepatitis (CH) patients.
- Serum HGF levels correlated positively with the degree of intrahepatic inflammatory cell infiltration and fibrosis.
- Intrahepatic HGF was primarily localized to the cell membrane of mesenchymal cells in areas of focal necrosis and showed increased expression in patients with higher serum HGF levels. In HCC, HGF was noted in infiltrating mesenchymal cells, not cancer cells.
Conclusions:
- Serum HGF measurement is a valuable tool for estimating the extent of intrahepatic inflammation and fibrosis in Hepatitis C patients.
- Elevated serum HGF levels may indicate a high carcinogenic state in chronic hepatitis and liver cirrhosis type C, warranting further investigation.
- HGF's role in HCC appears linked to tumor microenvironment modulation by mesenchymal cells rather than direct cancer cell proliferation.
Abstract:
We determined hepatocyte growth factor (HGF) levels in the serum and liver of patients with hepatitis C and assessed the relationship to histological findings of the liver and hepatitis C virus-related markers in the serum in patients with type C liver diseases. The subjects were 108 patients with chronic hepatitis C (CH), 70 patients with liver cirrhosis C (LC), 38 patients with hepatocellular carcinoma (HCC) and 20 patients with acute hepatitis (AH). As normal controls 20 subjects were studied. The serum HGF levels were measured using an enzyme-linked immunosorbent assay kit. Intrahepatic HGF was investigated by immunoperoxidase staining using monoclonal HGF antibody. The serum HGF level was highest in patients with AH. The serum HGF levels tended to be higher in patients with LC and HCC than those with CH. Further, the serum HGF level was related to the degree of intrahepatic inflammatory cell infiltration and fibrosis, and intrahepatic HGF was noted primarily in the cell membrane of mesenchymal cells in focal necrosis. The degree of intrahepatic HGF expression tended to be higher in patients with high serum HGF levels. In patients with HCC, however, HGF showed little localization in cancer cells, but was noted in infiltrating mesenchymal cells in both cancerous and noncancerous regions. In conclusion, the measurement of serum HGF levels may be useful for estimating the degree of intrahepatic inflammatory reaction and fibrosis. Although further study is necessary, the high serum level of HGF revealed high carcinogenic states in chronic hepatitis and liver cirrhosis type C.
