Immunosuppressive effect of chenodeoxycholic acid on natural killer cell activity in patients with biliary atresia and hepatitis C virus-related liver cirrhosis.
Patients with severe liver diseases, such as liver cirrhosis and biliary atresia, have low natural killer (NK) cell activity. The relations between NK activity and measures of liver function, including serum levels of total bilirubin, total bile acids, bile acid components, aspartate aminotransferase, and alanine aminotransferase, and platelet count were examined in patients with biliary atresia (6 boys and 6 girls; mean age, 4.8+/-5.7 years) and patients with liver cirrhosis due to hepatitis C virus infection (10 men and 2 women; mean age, 54.3+/-13.8 years). Univariate analysis showed that platelet count was positively correlated with NK activity in patients with biliary atresia (r = 0.611, P < 0.05). Serum levels of free chenodeoxycholic acid were negatively correlated with NK activity both in patients with biliary atresia (r = -0.647, P < 0.05) and in patients with hepatitis C virus-related liver cirrhosis (r = -0.876, P < 0.01). None of the other free bile acids or conjugated bile acids or other indicators of liver function were correlated with NK activity. Multiple stepwise regression analysis showed that only levels of free chenodeoxycholic acid were independently correlated with NK activity. All patients with biliary atresia underwent liver transplantation from living related donors. NK activity had increased significantly two months after transplantation (from 24.1+/-20.2% to 49.2+/-12.5%, P < 0.01). In contrast, levels of free chenodeoxycholic acid in transplant recipients had decreased significantly two months after transplantation (from 1.22+/-1.16 to 0.26+/-0.21 micromol/l, P < 0.05). In conclusion, in patients with biliary atresia or liver cirrhosis, NK activity in peripheral blood decreases, mostly because of free chenodeoxycholic acid.
Hirata
Masaru
M
Liver Transplantation Team, Graduate School of Medicine, University of Tokyo, Japan.
Harihara
Yasushi
Y
Kita
Yoshiaki
Y
Saito
Shoichi
S
Nishimuraj
Motoko
M
Yoshino
Hiroyuki
H
Sano
Keiji
K
Ito
Mitsuhiro
M
Kusaka
Koji
K
Kawarasaki
Hideo
H
Hashizume
Kohei
K
Makuuchi
Masatoshi
M
D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001647:Bile Acids and Salts / Q000097:blood; D001656:Biliary Atresia / Q000097:blood / Q000276:immunology* / Q000601:surgery; D001663:Bilirubin / Q000097:blood; D002635:Chenodeoxycholic Acid / Q000097:blood*; D002675:Child, Preschool; D005260:Female; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology / Q000276:immunology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D012044:Regression Analysis
D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin