Clinical Study Of Cylex(?) Immuknow Cell Function Test For Patients Undergoing Liver Transplantation

Background:Acute cellular rejection is one commonly morbidity after liver transplantation.If not to be diagnosed and treated timely,sever rejection will threat the patient's life and turn to chronic rejection which can lead to graft loss.Such rejection is mainly mediated by T cells, and most of the immunosuppresants which are used in transplantation clinic and researched in lab take effect by restraining the active and effective function of the T cells.CD4~+T lymphocytes are considered to be the key role to initiate the cellular rejection,which can identify the transplant antigen presented by Antigen Present Cells(APC),then start the immunologic response.Therefore,CD4~+T lymphocytes are very important in the immunologic response after liver transplantation,and measurement of the CD4~+T lymphocyte's activation can reflect the function of immunologic cells.Food and Drug Administration of American(FDA) once concluded that blood concentration of the immunosuppresants can't be used as the only index of the drug's adjustment,and an overall evaluation must be done before adjustment of drugs in the transplanted patient.Cylex(?) immuknow cell function test has been cleared by FDA,which can evaluate the recipient's immunologic function through whole blood analysis and enable the individualized management of the patients after organ transplantation.Objective:To explore the evaluation of Cylex(?) immuknow cell function test for Chinese patients undergoing liver transplantation.Method:We tested 309 blood samples by Cylex(?) immuknow cell function test collected from 74 patients who received liver transplantation between April of 2004 and April of 2008.There are 61 males and 13 females in those patients,aged from 28 years to 71 years old,their average age is 49.2±13.5 years.The primary diseases including hepatocellular carcinoma(n=48),hepatitis B-related liver cirrhosis(n=19),primary biliary cirrhosis(n=2),cholangiocarcinoma(n=2),primary sclerosing cholangitis(n=2),alcoholic liver cirrhosis(n=1) and fulminant hepatitis(n=1),respectively.At the same time we tested the blood samples of 56 health adults,including 32 males and 24 females,the age of those adults ranged from 21 to 65,and the average age of them is 41.0±13.5 years.The data base including issues of the age and sex of the patients,the time of the operation,primary disease,the time of the testing,the relative ATP levels and blood concentration of the drugs, the patient's condition during the test(stable,rejected or infected), the dosage of the immunosuppressants,the percentage of CD4+T cells,tumor recurrence,chemotherapy,and the level of total bilirubin/ direct bilirubin,alanine aminotransferase(ALT) level and so on.Then we carry out statistic analysis on the base of those datas.Results:The average ATP level of health adult is 257±97ng/ml,which is lower than 415±100ng/ml reported by Europe and USA researches.The average ATP level of patients with stable liver function and general condition after liver transplantation in our Institution is 209±59ng/ml,also lower than 249±99ng/ml reported by the westerners.We found immunologic function and the percentage of CD4+T cells do not have liner correlation through scatter graph.Pearson correlation analysis(P＞0.05) and liner regression analysis proved that result.We also found that ATP level has the correlative relationship with FK506 blood concentration(P＜0.05) but do not has the correlative relationship with Rapamycin blood concentration (P＞0.05).The ATP level of stable,rejected and infected patients after liver transplantation has also been compared.The average ATP level of three group is 209±59ng/ml,594±110ng/ml,60±25ng/ml respectively,and comparision among the groups has statistical significance(P＜0.05).We tested 33 samples from 12 patients suffered from tumor recurrence or metastasis validated by typical image or pathology evidence,and 45 samples of 20 stable patients.Average ATP level of the two groups is 154±88ng/ml and 209±59ng/ml,the recurrence or metastasis group has the lower ATP level(P=0.001).The ATP level before and after the transplantation were detected and compared in 14 liver cancer patients undergoing liver transplantation from January to April of 2008.The average level before and after the operation is 183±58ng/ml and 217±66ng/ml respectively,and the ATP level after the operation is higher than that before the operation in spite of the immunosuppressants (P=0.014).According to the experience reported by foreign documents,we classified 309 data detected by Cylex(?) immuknow cell function test into three groups:ATP level＜100ng/ml(group 1),ATP level=100-300 ng/ml (group 2),and ATP level＞500 ng/ml(group 3),corresponding to infection, stable,and rejection respectively.Logistic regression analysis indicated that compared to group 2,group i has the higher infection risk (OR=8.7),while group 3 has the more higher rejection risk(OR=19).We also adjusted the dosage of immunosuppressants according to ATP level we got through Cylex(?) immuknow cell function test in some patients and got the success.Conclusion:Cylex(?) immuknow cell function test can be an effective method to assess the immunologic function after liver transplantation.Combined the tests of Cylex(?) immuknow cell function and immunosuppressant drug concentration we can evaluate the immunologic response of liver recipients more accurately and adjust the drug more precisely,and could predict the risk of rejection,infection and the tumor recurrence.Therefore,Cylex(?) immuknow cell function test should be used in a more extended way in liver transplantation clinic.The novelty of this work:This is the first time that Cylex(?) immuknow cell function test be used in China to assess the immunologic function in liver recipients.