title: Combination assays for evaluation of immune function and CYP3A5 genotype to identify the risk of infectious complications and mortality in living donor liver transplant patients.
abstract: BACKGROUND
  The aim of this study is to evaluate whether the combination of the ImmuKnow assay (IMK) and cytochrome P450 3A5 (CYP3A5) genotype assay is useful for identifying the risk of morbidity and mortality in living donor liver transplantation (LDLT) patients, and also to investigate the optimal cutoff value of IMK level of immune status.
  
  
  METHODS
  Sixty six LDLT patients, who were randomly screened by using IMK between March 2002 and June 2011, were divided into 2 groups: patients in whom at least 1 IMK value was <175 ng/mL (Group A, n=16) and patients in whom all IMK values were >175 ng/mL (Group B, n=50). Both donors and recipients were evaluated for the CYP3A5 genotype.
  
  
  RESULTS
  The frequencies of cytomegalovirus and bacterial infection in Group A were significantly higher than those in Group B (P<0.001). The short term mortality was 4 (25.0%) in Group A and none in Group B, and the IMK level in all four cases became <100 ng/mL at least one time before death. The rate of CYP3A5*1 allele (expressors) among recipients was significantly higher in Group A than in Group B (63.6% vs. 22.2%, P=0.0147). The rates of CMV infection and bacterial infection, and the IMK levels was significantly higher in recipients with expressors (p=0.0216, p=0.0332, and p=0.0433, respectively).
  
  
  CONCLUSIONS
  The combination of the IMK and CYP3A5 genotype assay is useful for monitoring immune status after LDLT, and the IMK level <100 ng/ml might be the critical level to make a recovery from the severe immunesupressive condition.
authors.affiliation: mizunos @clin.medic.mie-u.ac.jpDepartment of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan.
authors.forename: Shugo
authors.initials: S
authors.lastname: Mizuno
authors.forename: Kaname
authors.initials: K
authors.lastname: Nakatani
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Muraki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tanemura
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Azumi
authors.forename: Naohisa
authors.initials: N
authors.lastname: Kuriyama
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ohsawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Kishiwada
authors.forename: Masanobu
authors.initials: M
authors.lastname: Usui
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Masami
authors.initials: M
authors.lastname: Tabata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okuda
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nobori
authors.forename: Shuji
authors.initials: S
authors.lastname: Isaji
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001424:Bacterial Infections / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000209:etiology; D005260:Female; D005838:Genotype; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D007223:Infant; D007239:Infections / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D016031:Liver Transplantation / Q000009:adverse effects* / Q000401:mortality*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus