Metabonomic Study Reveals Ratio Of Serum Lactate To Creatinine As A Potential Therapeutic Marker In Patients With Liver Failure Treated By Artificial Liver Support System

Objective:To date,few studies have been conducted on the evaluation indicators of the therapeutic effect of artificial liver support system.In this paper,nuclear magnetic resonance(~1HNMR)based metabolomics was employed to identify and screen biomarkers for differentiating patients with hepatic failure before and after artificial liver support system(ALSS)treatment,which would provide reference for the evaluation of therapeutic efficacy of artificial liver support system treatment.Method:1.About 200 serum samples were collected from patients with liver failure and100 healthy controls.57 cases in the experimental group and 50 cases in the control group were matched.In addition,more than 300 cases of clinical data and prognosis for survival or death were retrospectively analyzed.The serum samples of patients with liver failure before and after ALSS treatment were analyzed by ~1HNMR based metabonomics,and the differential metabolites and accociated metabolic pathways were identified.2.The correlation between serum differential biomarkers and MELD score,PTA,survival time was analyzed,and the clinical retrospective analysis data were used to verify the efficacy of biomarkers in ALSS therapy.Result:1.The levels of leucine/creatinine,isoleucine/creatinine,acetate/creatinine,alanine/creatinine,creatinine/creatinine,taurine/creatinine and lactate/creatinine in patients with liver failure were significantly altered before and after ALSS treatment.Ratios of creatine/creatinine,taurine/creatinine and lactate/creatinine returned to normal levels After ALSS treatment.The AUROC of the three variables for differentiating the groups before and after ALSS treatment were 0.633,0.644 and0.650 respectively,which were higher than that of MELD score and PTA,indicating that these three indicators was able to differentiate the group of pre-and post-ALSS treatment,among which lactate/creatinine was the best.2.The ratio of lactate to creatinine was positively correlated with MELD and PTA.A retrospective analysis of 158 clinical data showed that the serum lactate/creatinine ratio in patients with liver failure before artificial liver treatment was 0.038±0.002 in survival group,0.048±0.005 in three-month and 0.052±0.005one-month death group.The serum lactate/creatinine ratio in death group was significantly higher than that in survival group,and was significantly correlated with the survival time(R=-0.26,p=0.001),indicating lactate/creatinine ratio can be used as a biomarker for evaluating the therapeutic effect of ALSS treatment.3.A prospective study was designed to screen 58 patients with liver failure whose PTA was between 9.0 and 40.0 before ALSS treatment.Results of statistical analysis showed that there was no difference in serum PTA and lactate/creatinine between the survival group and the one-month death group before ALSS treatment.There was also no significant difference in serum PTA between survival group(46.8±1.5)and death group(45.9±1.2);however,there was significant difference in serum lactate acid/creatinine between survival group and death group(0.029±0.004vs 0.049±0.007).Moreover,lactate/creatinine has a higher diagnostic efficiency than PTA in prognosis(AUROC:0.682 vs 0.594).Our results showed that serum lactate/creatinine was more sensitive than PTA in evaluating the therapeutic effect of ALSS,which further validate that lactate/creatinine could be used as a potential biomarker for evaluating the therapeutic effect of ALSS treatment.Conclusion:The lactate/creatinine ratio can be used as a biomarker for evaluating the therapeutic effect of ALSS treatment for patients with liver failure.Our results provide key information for the precise treatment of patients with liver failure with good prognosis.