endothelin-1 and Hepatitis-C

Expression of endothelin receptors in terminal liver cirrhosis is not well investigated. The aim of this study was to investigate the expression of the endothelin type A receptor (ETAR) and endothelin type B receptor (ETBR) immunohistochemically using paraffin-embedded tissue sections from patents with terminal liver cirrhosis (TLC), non-terminal liver cirrhosis (NTLC) and non-cirrhotic liver fibrosis (NCLF) caused by hepatitis C viral infection.. Liver tissue sections from 38 autopsy cases, including 12 cases of NCLF (mild, moderate or severe liver fibrosis), 11 cases of NTLC and 15 cases of TLC, were stained using anti-ETAR and anti-ETBR antibodies after antigen retrieval. Double staining using antibodies to alpha-smooth muscle actin (ASMA) was also performed.. There were significantly fewer ETBR-positive cells in TLC compared with NTLC and NCLF. Numbers of ASMA-positive stellate cells expressing ETBR were also significantly lower in TLC. Therefore, the ETAR/ETBR ratio of sinusoidal cells is significantly higher in TLC than in NTLC and NCLF. ASMA-positive stellate cells showed similar evidence of ETAR and ETBR expression.. There is a difference in ETAR and ETBR expression among TLC, NTLC and NCLF: the ETAR/ETBR ratio is increased in TLC due to a relative decrease in ETBR expression. This finding may be useful for the diagnosis of TLC with regard to circulatory disturbances in the liver.

Topics: Aged; Aged, 80 and over; Autopsy; Endothelin-1; Female; Hepatitis C; Humans; Immunohistochemistry; Liver Cirrhosis; Male; Middle Aged; Receptor, Endothelin A; Receptor, Endothelin B; Terminally Ill

A balance between endothelins (ET) and nitric oxide (NO) might interfere with liver haemodynamics and disease progression in various liver diseases. Increased levels of endothelin 1 (ET-1) and nitrites and nitrates (NOx, the end products of NO metabolism) have been reported in hepatocellular carcinoma (HCC), but the balance has not been studied. The purpose of this study was to assess the ratio of NOx to ET-1 in patients with virus-related hepatocellular carcinoma and to investigate its correlation with the extent of the disease. Eighteen patients with virus-related HCC (six Okuda stage I, six Okuda stage II and six Okuda stage III) were included in the study and were compared with 22 patients with viral cirrhosis (14 decompensated, eight compensated) and seven normal controls. ET-1 was measured with an ELISA assay and NOx with a modification of the Griess reaction. Patients with virus-related HCC had the highest levels of circulating ET-1 and NOx (13.24 +/- 0.82 pg/ml and 112.28 +/- 18.56 micromol/l) compared to compensated cirrhosis (9.47 +/- 0.50 pg/ml, P < 0.004 and 54.47 +/- 2.36 micromol/l, P < 0.01), decompensated cirrhosis (9.57 +/- 0.32 pg/ml, P < 0.001 and 90.20 +/- 11.23 micromol/l, NS) and normal controls (8.84 +/- 0.61 pg/ml, P < 0.001 and 51.17 +/- 6.18 micromol/l, P < 0.01). There was a significant increase of ET-1 and NOx at HCC stage III compared to HCC stages I and II, cirhotics and controls. HCC stage III patients also had a NOx/ET-1 ratio that was higher than HCC stages I and II patients, normal controls and patients with compensated cirrhosis. Virus-related HCC patients have high levels of circulating ET-1, compared to compensated or decompensated cirrhosis. Highest levels of ET-1 are produced in Okuda III tumours. NOx are also increased but only in Okuda stage III tumours. The NOx/ET-1 ratio is increased in virus-related HCC and DC. This increase may account for the known increase in tumour blood flow.

Topics: Carcinoma, Hepatocellular; Endothelin-1; Female; Hepacivirus; Hepatitis B; Hepatitis B virus; Hepatitis C; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Nitrates; Nitrites