title: Deficiency in calcineurin activity in liver transplantation candidates with alcoholic cirrhosis or hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Laboratory of Pharmacology and Toxicology, Centre Hospitalier Universitaire Henri Mondor, Paris XII University, Créteil, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Blanchet
authors.forename: Monika
authors.initials: M
authors.lastname: Hurtova
authors.forename: Françoise
authors.initials: F
authors.lastname: Roudot-Thoraval
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Costentin
authors.forename: Camille
authors.initials: C
authors.lastname: Barrault
authors.forename: Hèlène
authors.initials: H
authors.lastname: Jouault
authors.forename: Fathia
authors.initials: F
authors.lastname: Medkour
authors.forename: Alexis
authors.initials: A
authors.lastname: Laurent
authors.forename: Christophe
authors.initials: C
authors.lastname: Duvoux
authors.forename: Anne
authors.initials: A
authors.lastname: Hulin
mesh_terms: 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
chemical_list: C120817:calcineurin phosphatase; D019703:Calcineurin; D010744:Phosphoric Monoester Hydrolases