Analysis Of Clinical Features Of Patients With Drug-Induced Liver Injury And Establishment Of Prediction For Severe Disease

Research background and purpose:In recent years,the incidence of drug-induced liver injury has been increasing year by year,which has attracted more and more attention.However,the pathogenesis of DILI has not been fully elucidated,and the clinical features are diverse.Most patients with mild to moderate injury have a good prognosis after drug withdrawal and symptomatic treatment,but some severe patients may rapidly progress to acute liver failure or even death within a few days of onset if diagnosis and treatment are not timely.Because it is impossible to predict the occurrence of drug-induced liver injury and accurately judge the severity of liver injury in the early stage.In this study,197 patients with DILI were retrospectively analyzed,the risk factors of severe DILI were screened and the prediction model was established to provide clinical basis for better diagnosis and treatment of DILI.Materials and Methods:In this study,197 patients diagnosed with drug-induced liver injury in our hospital from January 2015 to June 2022 were retrospectively analyzed.The clinical data of patients during hospitalization were collected,and their clinical characteristics were analyzed.According to the severity classification of drug-induced liver injury in China,the patients were divided into non-severe group(n=65)and severe group(n=132).The clinical characteristics of patients with severe injury were summarized,and the prediction model of severe drug-induced liver injury was established.Results:1.A total of 197 DILI patients were collected in this study,including 72 males(36.5%)and 125 females(63.5%).Male: Female =1:1.7.The average age of DILI is48.77±13.38 years old.DILI can occur at all ages,with the minimum age being 15 years old and the maximum age being 83 years old.The onset age of DILI is more common between 40 and 59 years old,and most of them are female.The median length of stay in hospital was 14 days(10-21 days),and there was no significant difference in length of stay in hospital between injury types(P=0.358).2.In this study,the top four drugs leading to liver injury were Chinese herbal medicine or Chinese patent medicine(88 cases,61.5%),anti-tuberculosis drugs and combination drugs(12 cases,8.4%),non-steroidal anti-inflammatory drugs(10 cases,7.0%),and cold drugs(9 cases,6.3%).The most common clinical classification was hepatocellular injury type(113/197,57.4%),followed by cholestatic type(49/197,24.9%)and mixed type(35/197,17.8%).3.There were significant differences in prealbumin,international standard ratio,alanine aminotransferase,and aspartate aminotransferase among different clinical types of DILI groups(P<0.05).However,there was no significant difference in age,gender,albumin,total bilirubin,direct bilirubin,gamma-glutamyl transpeptidase,total bile acid and length of hospital stay(P>0.05).Further analysis of biochemical indicators between groups showed that the alanine aminotransferase and aspartate aminotransferase in patients with hepatocellular injury were significantly higher than those in patients with cholestasis or mixed type(alanine aminotransferase: 885.10IU/L vs.97.50IU/L vs.332.60IU/L;Aspartate aminotransferase: 672.60IU/L vs.69.50IU/L vs.263.30IU/L,P<0.001).The alkaline phosphatase level of the cholestatic type was higher than that of the hepatocellular injury type(180.20IU/L vs.258.10IU/L,P<0.001).At the same time,Alanine aminotransferase(523.70IU/L vs.314.20IU/L)and aspartate aminotransferase(347.20IU/L vs.162.30IU/L)on the third day after admission were significantly lower than those at baseline.However,alkaline phosphatase was not significantly decreased(192.00IU/L vs.172.90IU/L),and total bilirubin had a tendency to increase compared with admission.4.Compared with the non-severe group,the patients in the severe group had a longer length of hospital stay(16.5 days vs.10 days,P<0.001),and higher MELD score,ALBI score,alpha-fetoprotein,aspartate aminotransferase,total bilirubin,direct bilirubin,indirect bilirubin,alkaline phosphatase,total bile acid,low-density lipoprotein cholesterol,and platelet count.The levels of albumin,prealbumin and high density lipoprotein cholesterol were lower(P<0.05).5.In this study MELD scores ranged from 0.41 to 26.45 points,with an average of10.84 points and a median of 10.87 points.The patients were divided into four groups according to the quartiles,and it was found that the levels of total cholesterol and high density lipoprotein cholesterol gradually decreased with the increase of the degree of liver injury(P<0.05).6.Correlation analysis showed that total cholesterol and high-density lipoprotein cholesterol in DILI patients were negatively correlated with liver function indexes(alanine aminotransferase,aspartate aminotransferase,total bilirubin,direct bilirubin)(P<0.05),and positively correlated with albumin,prealbumin,alkaline phosphatase,andγ-glutamyl transpeptidase(P<0.05).There was no correlation with total bilirubin,direct bilirubin,total bile acid(P>0.05).7.The area under the curve value of the new model for predicting severe liver injury in DILI patients was 0.961(95%CI: 0.932-0.990,P < 0.001),which had certain predictive value.The cut-off value of the new model was 0.43,and the sensitivity and specificity of predicting severe DILI were 94.9% and 87.8%,respectively.The accuracy of the new model is high and it can be used to guide clinical practice.Conclusions:1.In this study,the main pathogenic drugs of DILI were Chinese herbal medicine.It can occur in all ages,mainly in middle-aged and elderly women.The most common clinical classification was hepatocellular injury.2.This study showed that high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,total bile acids and prealbumin were independent influence factors for severe DILI.3.Lipid metabolism is related to the occurrence and development of DILI,and can be used as an evaluation index of liver injury degree and disease progression in DILI patients.The new prediction model combined with lipid index can better predict the risk of severe DILI.The cutoff value of the new model for predicting severe DILI was 0.43,and the AUC was 0.961(95%CI: 0.932-0.990,P<0.001),which was better than the prediction performance of total bile acid,MELD score,ALBI score,high-density lipoprotein cholesterol and proalbumin,and can be used as a new method to assess the severity of injury in patients with DILI.