The Association Between Abnormal Serum Bilirubin Levels And Clinical Characteristics Of Drug-induced Liver Injury

Objective:Drug-induced liver injury(DILI)is a common disease in gastroenterology department.Clinical methods used to determine the severity of DILI,clinical characteristics,and recovery,mainly include liver function biochemical tests with blood samples,imaging,and liver tissue biopsy.However,it is still unclear whether the abnormal types of blood biochemical test indicators have predictive value for the characteristics of the course of liver function recovery,and whether there are hints for the application of different hepatoprotective drugs.This study mainly explores whether serum bilirubin levels have a suggestive significance for the biochemical indicators of liver function,the course of disease recovery,and the choice of glucocorticoid(GC)therapy.Methods:This is a retrospective study.A total of 142 patients with DILI who were hospitalized in the Affiliated Hospital of Qingdao University from March 1,2013 to March 1,2019 were included.The following clinical data of patients were collected: 1)Gender,age,medical history(such as diabetes,cardiovascular and cerebrovascular diseases,autoimmune diseases,etc.),previous medication history;2)Serum biochemical indicators of liver function;3)The number of cases with biochemical indicators of liver function returned to normal levels;4)Length of hospital stay;5)The number of patients treated with GC.In this study,abnormal serum bilirubin criteria were defined as ALT ≥ 3ULN +TB ≥ 2ULN.The study subjects were divided into abnormal serum bilirubin group according to the presence or absence of abnormal biochemical indicators of serum bilirubin system.In addition,DILI patients with abnormal serum bilirubin levels were divided into two subgroups according to whether GC treatment was combined or not: GC treatment subgroup(GC)and non-GC treatment subgroup(NG),and the recovery of biochemical parameters of liver function,duration of disease,and GC treatment options were compared between these two subgroups.Results:1.A total of 142 patients with DILI were included in this study,including 46 males(32.39%)and 96 females(67.61%).There were 77 patients in the abnormal serum bilirubin level group and 65 patients in the normal serum bilirubin level group.There were 26 males and 51 females with abnormal serum bilirubin level,aged 24-74 years old,with mean age of(51.4 ± 12.6)years old;there were 20 males and 45 females with normal bilirubin level,aged 22-82 years old,with mean age of(55.5 ± 13.2)years old.2.The analysis results of the classification and constituent ratio of drugs inducing DILI showed that among the patients with normal serum bilirubin levels and abnormal serum bilirubin levels,there were many types of drugs causing DILI,and the proportions of traditional Chinese medicines,Chinese patent medicines and health products were much higher than those of other drugs(26 cases in normal serum bilirubin level group,(40.0%)and 32 cases in abnormal serum bilirubin level group(41.6%),respectively).The proportion of multidrug combination(15% versus 10.4%),antimicrobial agents(7.7%versus 7.8%),cardiovascular and cerebrovascular drugs(6.2%versus 5.2%),and anti-tumor drugs(4.6% versus 5.2%)was also relatively high in each group.There was no statistically significant difference in the proportion of inducing drugs between the two groups.3.The results of baseline characteristics analysis of biochemical indicators of liver function(AST、ALT、γ-GT、ALP)in DILI patients showed that,for at admission,among biochemical indicators of serum liver function,the levels of AST,ALT,ALPwere significantly higher in patients with abnormal serum bilirubin levels than that in patients with normal serum bilirubin levels(P < 0.05).The results of Pearson correlation analysis showed that the serum AST levels of DILI patients with abnormal serum bilirubin levels were positively correlated with TB levels(r = 0.235,P < 0.05).4.The analysis results of biochemical indicators of liver function(AST、ALT、γ-GT、ALP)showed that 1 week after hospitalization,the serum levels of ALT and AST in the two groups of patients with DILI were significantly lower than those before treatment(P< 0.01).The levels of γ-GT and ALP in DILI patients with abnormal bilirubin levels were significantly lower after treatment(P < 0.05).The percentage of decrease in AST levels in DILI patients with normal serum bilirubin levels was significantly higher than that in patients with abnormal bilirubin levels(P < 0.05).5.The average length of hospital stay was 15.59 days(8-28 days)in DILI patients with elevated serum bilirubin levels was longer than that in patients with normal bilirubin levels(10.87 days;6-25 days)(P < 0.05).In addition,the number of cases with complete recovery of liver function biochemical parameters(including ALT,、AST、γ-GT,and ALP)at discharge in DILI patients with abnormal serum bilirubin levels was significantly lower than that in patients with normal serum bilirubin level group(P < 0.05).The results of Pearson correlation analysis showed that the length of hospital stay of DILI patientswith abnormal serum bilirubin levels was positively correlated with serum TB levels(r = 0.525,P < 0.01).6.The analysis results of the application of GC treatment in patients showed that: 12 DILI patients(15.58%)with elevated serum bilirubin levels were treated with GC,which was significantly higher than that in the normal bilirubin group(1 case).The subgroup analysis showed that in DILI patients with elevated serum bilirubin levels: 1)the baseline levels of ALT,AST,IB,DB,TB and other liver function biochemical indicators in GC subgroup were significantly higher than those in NG subgroup(P < 0.01);2)the percentage of decrease of liver function biochemical indicators(ALT,AST,γ-GT,ALP,IB,TB)in GC subgroup was significantly higher than that in NG subgroup 1 week after hospitalization(P < 0.05).7.Among the 12 Dili patients who were treated with GC in the abnormal bilirubin group,only 1 Dili patient had hypokalemia during hospitalization,and no adverse reactions such as lower limb depression edema,infection,acute gastrointestinal bleeding,etc.Conclusion:1.There was no significant difference in the proportion of inducing drugs between the two groups of DILI patients.2.DILI patients with elevated serum bilirubin levels have higher baseline levels of biochemical markers of liver function.After treatment,the recovery of liver enzyme indicators was slower and the course of hospitalization was prolonged,suggesting that the degree of liver function injury was more severe,the recovery was slower,and the combination of GC was more preferred.3.In DILI patients with elevated serum bilirubin levels,patients treated with GC had higher baseline levels of serum liver enzymes,and the liver enzyme levels decreased more significantly after treatment.