Comparing The Diagnostic Role Of Three Diagnostic Scoring Systems Combined With Pathological Scores For Drug-induced Liver Injury

Background&Aims:Drug-induced liver injury(DILI)is a common adverse drug reaction(ADR),and it can lead to liver failure and even death.However,the current diagnosis of DILI still lacks a precise criterion,which lead to it's diagnosis mainly relied on exclusion of other diseases that cause liver damage.In this study,the clinical characteristics of patients diagnosed with definite DILI and suspected DILI were analyzed.Three clinical diagnostic scoring system were performed for each patient,and the diagnostic accuracy of DILI was compared between the three scoring systems.Then,liver biopsy was performed and scored by pathology score system.Aiming to explore how to diagnose DILI definitely,and provide a reference for clinicians.Methods:DILI patients admitted to Tianjin Second People's Hospital from 1,January 2012 to31,December 2017 were collected.340 patients was finally diagnosed with definitely DILI,and 118 with suspected DILI.Based on the criteria for the diagnosis and treatment of DILI in China,2007 and after the Multidisciplinary Team(MDT)consultation.MDT includes clinical hepatologists,infectious physicians,clinical pathologists and clinical pharmacists.All DILI patients were divided into 3 clinical groups according to their serum liver enzymes,and their differences in serum biochemistry were compared.Patients were scored by Roussel-Uclaf Causality Assessment Method(RUCAM),Maria&Victorino scale(Maria)and Digestive Disease Week-Japan criterion(DDW-J);liver tissue sections of DILI patients were observed,and pathological features were scored using a refined DILI pathology scoring system(rDILI-PSS).It's diagnostic value were evaluated.Combination of rDILI-PSS and clinical criteria used logistic regression.Kruskal-Wallis H was used for multiple analyses,Mann-Whitney U for between groups,and nonparametric tests were also used in case.The ROC curve was used to evaluate the diagnostic efficacy.P<0.05 was considered statistically significant.Statistical analysis was performed using SPSS 21.0 and MedClac 15.0 software.Results:1.Clinical characteristics of all DILI patients:458 DILI patients were enrolled.hepatocyte type was the highest,accounting for 290(63.32%),and mixed type accounted for 97(21.18%),and cholestasis types accounted for 71(15.5%).Chinese herbal medicine is the main cause of DILI,and female patients are more than male patients.The median(interquartile range)of the biochemical indicators in the three clinical subtypes were:ALT:1018.5(131,4435),253(48,1920),151(12,477)IU/L;AST:612.5(53,3045),175(28,1510),135(18,823)IU/L;GGT:207.5(17,1516.4),255(39,2652),295(25,888)IU/L;ALP:171.35(20,765),204(54,1240),265(64,1399)IU/L;TB:74.75(9.3,492.9),32.8(5.3,213.3),34.6(4.8,439.2)?mol/L;DB:56.1(3,365),12.3(1,142),11.1(1,358)?mol/L;Glu:5.33(3,16),5.53(4,29),5.42(4),17)mmol/L;TG:1.74(1,8),1.51(1,22),1.64(0,5)mmol/L;CHO:4.02(2,8),4.82(3,24),4.91(2,17)mmol/L.2.Accuracy of three DILI diagnostic criteria:Among the 458 DILI patients,340were diagnosed with definite DILI and 118 with suspected DILI.The scores(mean±standard deviation)of RUCAM,Maria and DDW-J were:8.04±1.66,11.59±2.63and 8.24±1.2,respectively.The AUROCs of the three criteria were:0.730(95%CI:0.667-0.793),Z=7.147,P<0.001;0.793(95%CI:0.740-0.847),Z=10.753,P<0.001;0.764(95%CI:0.702-0.826),Z=8.303,P<0.001,respectively3.Pathological features of three clinical subtypes and combined diagnostic efficacy:The pathological features of seven rDILI-PSS in 302 liver biopsies were:204(67.5%)manifested steatosis,?~2=4.487,P=0.106;151(50%)manifested cholestasis,?~2=3.886,P=0.143;139(46%)manifested apoptosis,?~2=0.840,P=0.657;131(43.4%)manifested eosinophil gramulocyte infiltration,?~2=0.30,P=0.985;103(34.1%)manifested central and/or portal phlebitis,?~2=25.948,P<0.001;90(29.8%)manifested iron deposition,?~2=5.737,P=0.057;92(30.5%)manifested wax-like deposition,?~2=6.616,P=0.037.The new parameters combined rDILI-PSS with RUCAM,Maria and DDW-J were expressed by logistic regression formula as:pre1=PSS+0.374*RUCAM,pre2=PSS+0.338*Maria,pre3=PSS+0.578*DDW-J.The AUROC of the three new parameters were:0.843(95%CI:0.747-0.914),Z=7.653,P<0.001;0.907(95%CI;0.822-0.960),Z=10.467,P<0.001;0.881(95%CI:0.790-0.942),Z=9.352,P<0.001Conclusion:Maria criterion is the most effective diagnostic scoring system in diagnose DILI definitely.in the three.After combined with rDILI-PSS,the diagnostic efficacy of the three diagnostic scoring systems have all improved and pre2(rDILI-PSS combined with Maria)has the highest diagnostic efficiency.