Imbalance between expression of endothelin receptors A and B in terminal liver cirrhosis due to hepatitis C viral infection: immunohistochemical study of autopsy cases.

Background And Aim: 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.

Methods: 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.

Results: 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.

Conclusions: 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.