Role Of CD14~+/HLA-DR Detection In Postoperative Infection Monitoring And Clinical Prognosis Evaluation Of The Patients With Orthotopic Liver Transplantation

Duo to the sevirity of primary disease and application of immunodepressive drugs, infection become a major factor to predict the outcome of patients undergoing postoperative liver transplantation. Sepsis, septic shock and MODS due to postoperative infection has become the most severe complication and mortality reason in postoperative patients.Because most preoperative patients have malnutrition and compromised immunity, and large dose of hormone and immunodepression are routinely used after operation, common parameters such as temperature, WBC count and CRP levels are not suitable to predict infection after operation. Although PCT has relatively high sensitivity and specificity, it has poor prediction power in diagnose fungal, virus and protozoan infection, meanwhile, complicated techniques and drug application make PCT a poor diagnostic indicator of fungal, virus and protozoan infection after operation. Besides, culture results takes time and have low positive rate, effective assisted diagnostic method is of great importance to differentiate rejection. At present, most researches about immuno-evaluation of postoperative patients focus on the rejection diagnosis, and there is no effective immuno-paremeter to predict postoperative infection. CTP scores are used in predict the severity of preoperative conditions of end-stage liver disease, and it has its certain limitations. CTP scores is short of validity in assessing non-cirrhosis, and lack of accuracy to predict the severity of patients especially in those combined with renal dysfunction. MELD score system is discussed in recent literatures and it is proved that it is more accurate in reflecting the pre-operative severity and renal functions in end-stage liver disease patients, and it is considered as a tissue-distribution standard and predicting-outcome factor. Due to tech complicity and indefinability of postoperative treatment and recovery, a new indicator is in great need to better predict the infection and outcome.CD14+/HLA-DR is proved to be effective in predicting the infection and outcome of sepsis patients due to trauma, shock and major operation, howere, there is seldom research about the CD14+/HLA-DR changes rule and its relationship with postoperative infection, clinical outcome and immuno-modulation. Our study analyzes dynamic changes of CD14+/HLA-DR and its relationship with postoperative infection, septic shock and clinical outcome in 91 cases of orthotopic liver transplantation patients, and provide new method in infection monitoring, predicting the outcome and evaluating the immunity in postoperative patients undergoing liver transplantation.To monitor the occurrence and clinical outcome of infection and septic shock patients after hepatic implantation, and detect the postoperative CD14+/HLA-DR expression and observe its effects in predicting the infection and outcome so as to calculate the responsive warning value. To observe the dynamic trend of CD14+/HLA-DR expression in different stage of patient with infection and septic shock and to observe the importance of predicting the condition, postoperative infection and treatment. To provide a new light in predicting the postoperative infection, determining the outcome and modulating the immunity in postoperative hepatic implantation patient.According to the definition of systemic infection and septic shock defined by ACCP/SCCM in 1998 and the protocol of hemodynamic monitoring and support guidance in adult with severe infection and septic shock released by affiliated critical care medical association of Chinese Medieal Association in Oct 2006,91 patients (80 of male,27-69 years of age,49.91±9.01 years of average age) in the end stage of hepatic disease after orthotopic hepatic implantation from Mar 2003 to Dec 2009 were divided into non-infection group (NI group,, n=62), infection group (I group,, n=13) and septic shock group (SS group, n=8). Unified case form was made, and age, sex, preoperative diagnosis, hospital stay, postoperative stay, ICU stay and clinical outcome were recorded. Flow cytometer were used to detect the CD14+/HLA-DR expression after implantation and at discharge, and detect again when infection occurred, most severed, relieved/persisted and at discharge or death in patients with infection and septic shock. The average value of CD14+/HLA-DR expression in different time point was adopted. The value of CD14+/HLA-DR expression when infection manifested the most severe according to the body temperature, hemogram, PCT, iconography and clinical manifestations was used in patients with infection and septic shock.. CD14+/HLA-DR expressions in different groups were compared, and ROC analysis was processed, so as to evaluate the prediction power in postoperative infection, infection shock and death and to calculate the optimal cutoff value. Based on the CD14+/HLA-DR expression distribution, patients were divided into 3 groups, and the outcome is compared and the Pearson relative analysis was used to assess the relationship between the CD14+/HLA-DR expressions, hospital stay, postoperative stay and ICU stay in order to evaluate the importance of CD14+ HLA-DR expressions in predicting outcome. CD14+/HLA-DR expressions at different time point before and after implantation in 3 groups was compared to analyze its role in determine the condition, adjusting the treatment and regulate immunity.SPSS13.0 was used, andχ2 test was used in comparison of sex among three groups. Data were presents with x±s, and One-way ANOVA was applied in mean value comparison. LSD was used in multiple comparisons. ROC curve assay was applied to evulate HLA-DR expression in prediction of outcome. Pearson analysis was usted to test the corelationships between general parameters and CD14+/HLA-DR. P<0.05 was considered to have statistical significance.1 The infection occurrence after liver transplantation:25 cases of postoperative infection (11 of septic shock) were developed in 91 cases after hepatic implantation, with infection rate of 27.5%. 9 cases are multi-site infection (occurrence rate of 36.0%), with pulmonary infection of 5 cases, hematogenous infection of 5 cases, celiac infection of 4 cases, biliary infection of 2 cases. Bacteria infection accounts most in pathogenesis (bacteria infection rate of 84%), including 4 cases combined with deep fungal infection (combind infection rate of 16%),3 cases of cytomegalorivus infection,1 cases of HCV infection.8 patients died with mortality rate of 8.8%.2 Groups of patients with liver transplantation:In the NI group, CD14+/HLA-DR expressions have no difference with that of healthy controls (66.26±18.21% vs 62.3±9.71%, P>0.05). based on the different groups in CD14+/HLA-DR expression distributions and with infection or not, there is no difference in the sex rate and age in NI group, I group and SS group, as well as in the HLA-DR≥40% group,20%< HLA-DR<40% group and HLA-DR≤20% group, indicating there is comparability in different groups. 3 Co-relationship between CD14+/HLA-DR expression rate and infecting degree in liver transplantation:CD14+/HLA-DR expression in I group is much lower than that in the SS group (p<0.05), and those in both group are significantly reduced than that in NI group (P<0.01). the ROC of CD14+/HLA-DR expression to predict infection is 0.944, with standard error of 0.027 and 95% CI of (0.891, 0.996) indicating that CD14+/HLA-DR expression has an important role in predicting the occurrence of infection (P<0.01). The lower CD14+HLA-DR expression is, the greater possibility of infection the patient might have. The cutoff value of 42% is considered as the most optimal value to differentiate postoperative infection patient (sensitivity of 88%, specificity of 91%). Also, CD14+/HLA-DR expression is an effective biomarker in differentiating septic shock from infection patients (ROC of 0.952, standard error of 0.024,95% CI of (0.905,0.999), p<0.01), and the most optimal cutoff value is 33.5% (sensitivity of 90.9%, specificity of 88.7%).4 Co-relationship between CD14+/HLA-DR expression rate and the outcome of the patients with liver transplantation:The ICU stay, postoperative stay, infection rate and mortality rate in the 20%40% group (p<0.05), and mortality rate and infection rate in the treatment subgroup of HLA-DR<20% group are higher than those of 20%0.05).1 CD14+/HLA-DR expression is a useful biomarker in monitoring infection and septic shock after hepatic implantation. CD14+/HLA-DR≤42% can be considered as a warning threshold of infection occurrence. CD14+/HLA-DR≤35% can be considered as a warning threshold of septic shock occurrence.2 CD14+/HLA-DR expression has an important role in predict the outcome in the hepatic implantation patients. Low CD14+ HLA-DR expression is associated with prolonged ICU stays, postoperative stays and hospital stays, as well as high mortality rate and high infection rate. CD14+/HLA-DR≤39% is a warning threshold to predict mortality.3 Dynamic monitoring of CD14+/HLA-DR expression is of great importance in the guidance of determine severity and adjust treatment for high-risk and suspicious postoperative infection patients. Decreased CD14+/HLA-DR expression is a general hint of infection and septic shock occurrence and poor outcome, and immunodepressive drugs should be decreased or even discontinued, with prompt application of immunostrengthening medications, acute reject reaction occurrence is not concerned. After immunomodulatory treatment, graveled CD14+/HLA-DR expressions indicate improved state whereas decreased or persisted low CD14+/HLA-DR expression represent poor outcome.