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Deficiency in calcineurin activity in liver transplantation candidates with alcoholic cirrhosis or hepatocellular carcinoma
Author(s) -
Blanchet Benoit,
Hurtova Monika,
RoudotThoraval Françoise,
Costentin Charlotte E.,
Barrault Camille,
Jouault Hèlène,
Medkour Fathia,
Laurent Alexis,
Duvoux Christophe,
Hulin Anne
Publication year - 2009
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2009.02084.x
Subject(s) - hepatocellular carcinoma , calcineurin , liver transplantation , cirrhosis , medicine , alcoholic liver disease , peripheral blood mononuclear cell , gastroenterology , tacrolimus , phosphatase , analysis of variance , transplantation , endocrinology , phosphorylation , biology , in vitro , biochemistry
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. Patients and 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). Conclusion: 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.