Deficiency in calcineurin activity in liver transplantation candidates with alcoholic cirrhosis or hepatocellular carcinoma.
BACKGROUND
Tacrolimus and cyclosporin inhibits the activity of calcineurin, a serine/threonine phosphatase that is involved in many physiological and pathological pathways. However, the baseline calcineurin phosphatase activity (CPA) measured before the transplant is unknown. In this study, we determine baseline CPA in liver transplant (LT) candidates and explore some factors that might modify it.


METHODS
Thirty-two consecutive LT candidates (25 men, seven women, average age 53.4 years) were included. Seven millilitres of whole blood was collected from each patient. CPA was determined in lymphocytes quantifying a dephosphorylated peptide phosphorylated previously (D-L-D-V-P-I-P-G-R-F-D-R-R-V-S-V-A-A-E) by high-performance liquid chromatography. The relationship between CPA and the quantitative variables was tested according to Pearson's correlation. A two-way analysis of variance was performed to test the independent role of categorical parameters in CPA.


RESULTS
The median CPA was significantly lower in LT candidates than in healthy volunteers [179.2 (146.9-226.3) vs 247.8 (220.9-292.5) pmol/min/10(6) peripheral blood mononuclear cell (PBMC), respectively, P=0.0002]. CPA was also significantly lower in alcoholic cirrhosis (152.2 vs 211.1 pmol/min/10(6) PBMC, P=0.04) and in the presence of hepatocellular carcinoma (HCC) (152.0 vs 213.5 pmol/min/10(6) PBMC, P=0.0074) compared with other liver diseases. A two-way analysis of variance showed that these parameters were independently associated with lower CPA (P=0.05 for alcohol and P=0.0056 for HCC respectively).


CONCLUSIONS
This pilot study showed a lower CPA in patients with AC and HCC. This phenomenon may contribute towards lowering the risk of acute rejection in these patients after LT and, on the other hand, may increase the risk of de novo cancers.
Blanchet
Benoit
B
Laboratory of Pharmacology and Toxicology, Centre Hospitalier Universitaire Henri Mondor, Paris XII University, Créteil, France.
Hurtova
Monika
M
Roudot-Thoraval
Françoise
F
Costentin
Charlotte E
CE
Barrault
Camille
C
Jouault
Hèlène
H
Medkour
Fathia
F
Laurent
Alexis
A
Duvoux
Christophe
C
Hulin
Anne
A
D000328:Adult; D000368:Aged; D019703:Calcineurin / Q000097:blood* / Q000172:deficiency; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000601:surgery; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood* / Q000601:surgery; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000097:blood* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010865:Pilot Projects; D055815:Young Adult
C120817:calcineurin phosphatase; D019703:Calcineurin; D010744:Phosphoric Monoester Hydrolases