Association Of Risk Factors And Abnormal Liver Function/DILI Happened After Oxaliplatin-Based Chemotherapy In Colorectal Cancer Patients

Purpose:With the aim of exploring the main risk factors inducing abnormal liver function/DILI after using oxaliplatin-based chemotherapy in colorectal cancer patients, as well as the therapeutic effect of some hepatic protection agents, we established binary logistic regression models and multivariable linear regression equations which could predict the incidence of abnormal liver function/DILI, in order to find risk factors.Methods:We did a retrospective analysis between 267 colorectal cancer patients treated with oxaliplatin-based chemotherapy in Qilu Hospital of Shandong University from January 1st 2014 to December 31th 2015. We monitored the liver function and other side effects of each patients before and after every cycle of chemotherapy. Patients were classified into 3 groups:normal liver function group, abnormal liver function group, and DILI group according to the Paris Consensus about DILI made by experts from the United States & European Countries in 1989. After getting the agreement of patients, we collected 2 milliliter of blood from peripheral venous and tested the genotype of XRCC1 Arg399Gln. For each patient, a detailed record about 34 factors that might affect the occurrence of abnormal liver function/DILI was noted, which could be concluded into 6 aspects, general factors, liver condition, tumor features, therapeutic regimen, XRCC1 Arg399Gln genotypes(only for those who agree with the blood test) and hepatic protection agents(only for those in abnormal liver function group or DILI group). SPSS 17.0 software was used for statistical analysis of data. We established binary logistic regression models about the occurrence of abnormal liver function/DILI, the relationships between latency time and its median, the relationships between duration time and its median and the relationships between the differences of liver function after using hepatic protection agents for 6 weeks and its median, got the prediction probabilities from the probability equations, and evaluated the models by the AUC of ROC curves. Meanwhile, we set multivariate linear regression equations to evaluate the latency times, duration times of abnormal liver function/DILI, and the differences of liver function after using hepatic protection agents for 6 weeks, got regression equations, and evaluated the fitness degree of equations with coefficient R2. Finally, we try to find related risk factors through these models and regression equations.Results:The occurrence of abnormal liver function/DILI after chemotherapy:The factor got into the model equation of the occurrence of abnormal liver function after chemotherapy was without the prevention using reduced glurathione, and the prediction accuracy was 70.1%. The factor got into the model equation of the occurrence of DILI after chemotherapy was age female, and the prediction accuracy was 64.8%. The factors got into the model equation of the occurrence of abnormal liver function or DILI were female, with liver metastasis, no more than high differentiation, without the prevention using reduced glurathione, with a prediction accuracy of 69.7%.The latency times of abnormal liver function/DILI after chemotherapy:The latency times of abnormal liver function group and DILI group do not make any difference. Regimen not XELOX(±Avastin) wasthe factor got into the regression equation of cumulative dose of oxaliplatin when abnormal liver function occurred after chemotherapy, with a fitness degree of 9.4%. Regimen not XELOX(±Avastin) was also the only one factor entered the model of the cumulative dose of oxaliplatin larger than its median when abnormal liver function occurred after chemotherapy, with a predication accuracy of 59.7%. Regimen not oxaliplatin and tegafurwas the only one factor entered the regression equation of cumulative dose of oxaliplatin when DILI occurred after chemotherapy, with a fitness degree of 32.4%. Male was regarded as the only one factor entered themodel of the cumulative dose of oxaliplatin larger than its median when DILI happened after chemotherapy, with a predication accuracy of 66.8%. Regimen not XELOX(±Avastin) was also included in the regression equation of time from the first cycle hen abnormal liver function happened after chemotherapy, with a fitness degree of 7.5%. And finally, male entered the model of the time from the first cycle more than its median when DILI happened, leading to an accuracy of 66.8%The duration times of abnormal liver function/DILI after chemotherapy:The duration times of DILI group are shorter than that of abnormal liver function group. With the treatment of diammonium glycyrrhizinate entered the regression equation of duration cycles when abnormal liver function happened after chemotherapy, with a fitness degree of 13.0%. BMI no less than 28, stage 4 entered the regression equation of duration cycles when DILI happened after chemotherapy, with a fitness degree of 32.5%. With the treatment of hepatic prediction agents entered the model of duration time more than its median when abnormal liver function happened after chemotherapy, leading to an accuracy of 61.2%.The therapeutic effects of hepatic prediction agents used from the occurrence of abnormal liver function/DILI after chemotherapy:Hepatic grediction agents are more polularly used in DILI group compared with abnormal liver function group. The therapeutic effects are more significant among DILI group than abnormal liver function group. With the treatment of silibinin entered the regression equation of the difference of ASTafter using hepatic protection agents for 6 weeks from the time of the abnormal liver function happened, and its fitness degree was 18.4%. Besides, the treatment of bifendate got into the regression equation of the difference of TBIL after using hepatic protection agents for 6 weeks from the time of the abnormal liver function occurred, with a fitness degree of 9.1%.Conclusion:Four factors, including female, with liver metastasis, no more than high differentiation, without the prevention using reduced glurathione, are critical to the occurrence of abnormal liver function/DILI after chemotherapy. No more than high differentiation, regimen not XELOX (±Avastin) are critical to short latency before the happening of abnormal liver function/DILI after chemotherapy. Long duration time of abnormal liver function after chemotherapy is related to BMI no less than 28, and stage 4. With the treatment of silibinin, or bifendate are critical to better therapeutic effects of hepatic protection agents’used from the occurrence of abnormal liver function/DILI after chemotherapy.