Clinical Features And Risk Factors Of Chemotherapy-induced Liver Dysfunction Of Colorectal Cancer Patients

Objectives:Oxaliplatin,irinotecan and 5-fuorouracil are widely applied to chemotherapeutic regimens for colorectal cancer.According to some research,however,their application can induce liver injury.Patients with colorectal cancers can benefit from chemotherapy,but liver injury induced by chemotherapy can lead to the delay of effective therapeutic measures,which may exacerbate the conditions of patients.Therefore,evaluating the clicical features and exploring the risk factors of chemotherapy-induced liver injury are significant for preventing and reducing hepatic injury.The objective of our study is to research the incidence,clinical manifestation and main risk factors of liver dysfunction induced by chemotherapy in colorectal cancer patients.What's more,we attempt to illustrate the influence of genetic variants in glutathione-S-transferases(GSTs)genotype on the occurrence of chemotherapy-induced liver injury.Methods:We performed a retrospective study of 505 colorectal cancer patients receiving standard chemotherapy in QiLu Hospital from Jan 1st 2014 to Dec 31th 2016.We collected clinical medical records which can be categorized as 4 aspects of host factors,liver status,tumor features and therapeutic regimens.We evaluated the liver function of each patient after every cycle of chemotherapy.The patients with abnormal liver function were categorized as case group,and the others were categorized as control group.We performed the univariate and multivariate analysis to illustrate the relationship between these factors and the occurrence of liver dysfunction.For those who agreed with the test of GSTs genotype,we collected blood sample and detected the variation of GSTM1 and GSTT1 genotype,then did correlation analysis.Results:1)505 patients received a total of 3277 cycles of chemotherapy.The incidence rate of liver dysfunction in colorectal cancer patients receiving chemotherapy was 55.25%(279/505),and the rate of liver injury was 13.66%(69/505).Among the patients with liver injury,there were 260 patients in grade 1 liver dysfunction,14 in grade 2,4 in grade 3,and 1 in grade 4.Most of the patients had hepatocellular DILI(56 patients),while 11 patients with cholestatic DILI and 2 patients with mixed-type.2)The univariate analysis showed that age,diabetes,combination with other drugs,type of treatment,chemotherapy drugs,chemotherapy regimens,and usage of target drugs were significantly associated with morbidity.The binary logistic regression analysis showed that age<60,diabetes,combination with other drugs were risk factors of chemotherapy-induced liver dysfunction.3)The frequency of GSTM1 null genotype was 46.43%.The frequency of GSTT1 null genotype was 58.33%.And the frequency of double null genotype was 30.95%.Correlation analysis showed that there was a higher risk of chemotherapy-induced liver dysfunction for colorectal cancer patients with GSTM1 null genotype and double null genotype.Conclusions:The incidence rate of chemotherapy-induced liver dysfunction with colorectal cancer patients was 55.25%,and the rate of liver injury was 13.66%?Three factors,including age<60,diabetes,combination with other drugs,were risk factors for the occurrence of chemotherapy-induced liver dysfunction.There was a higher risk of liver dysfunction for colorectal cancer patients with GSTM1 null genotype and double null genotype.