Investigation Of Clinical Features Of Drug-Induced Liver Injury In Elderly And The Establishment Of Prediction Model For Liver Failure

Background:As we grow elder,the volume of liver and the blood flow decrease as well,which weaken the activity of cytochrome P450 and further impair the metabolism drug.At the same time,due to decreased kidney removal ability,drugs and their metabolites are easier to accumulate in the body.In the meanwhile,the old are more likely to suffer from all kinds of chronic disease and have to take many drug for a long time.All these factors increase the possibility of drug induced liver injury in the old people.So this study aims to retrospectively analyze the clinical data of 97 cases of drug induced liver injury and causative agents in elderly.Methods:Firstly,we choose the patients that older than 60 years and the first diagnose is drug-induced liver injury or drug-induced hepatitis in the first affiliated hospital of school of medicine of Zhejiang university from 2013 to 2016.Then we analyze the factors include age,gender,the kind of drug,clinical types,laboratory index,imageological examination,duration of hospitalization,histological examination and the prognosis.Further,we summarize the traits of drug induced liver injury in the old people and the relevant factors that influence the prognosis,then we establish the prediction models for drug induced liver failure,which may instruct us to prevent and treat the drug induced liver injury.Use the chi-square test,rank and inspection,single factor analysis,logistic regression analysis to analyze the data in the statistical software SPSS 18.0.Results:Clinical features of drug induced liver injury:(1)General Information and clinical types This study included 97 patients,47 patients(48.5%)of men and women 50 cases(51.5%),the male to female ratio of 1:1.6.Their ages range from 60 to 92 years old,the average age was 72.1±8.0 years old.According to the clinical types of DILI:hepatocellular injury 54 cases(55.7%),cholestatic injury 12 cases(12.4%),mixed liver injury 4 cases(4.1%),abnormal liver biochemistry 27 cases(27.8%).Hepatocellular injury is the main clinical types in each age group,accounting for 64%,51%,47%of the group respectively.Underlying diseases were high blood pressure,diabetes,etc.:Simultaneous medication included cardiovascular,respiratory,antidiabetic medicines,health products,etc.20 cases had a history of alcohol,accounting for 20.6%,but they all failed to meet the diagnostic criteria for alcoholic liver disease.(2)Drug types that inducing liver injury The most common drug types are traditional Chinese medicine 54 cases(55.7%),anti-tuberculosis drugs,8 cases(8.2%),proprietary Chinese medicine,8 cases(8.2%),etc.;According to the dosing way:93 cases(95.9%)patients for oral use of drugs,4 cases(4.1%)for intravenous use of antibiotics.(3)The clinical manifestations and hospital stays The incipient symptoms and signs are nonspecific.The most common is yellow urine,yellow skin,yellow eye,fatigue,anorexia,abdominal distension.Extrahepatic symptoms are followed by pruritus,fever,rash.6 cases(6.2%)have no obvious symptoms except for the abnormal biochemistry.The incidence of liver failure was 21.6%,13 cases of acute liver failure,8 cases of subacute liver failure.Primary liver damage drugs used to starting symptoms shortest time for 2 days,up to 1 year.The longest hospital stay is 106 days,shortest for 2 days,the average was 20.4±16.3 days.Hospital stays have no significant difference between different gender and clinical types(P>0.05).(4)Laboratory examination The frequencies of the laboratory abnormalities in the drug induced liver injury in elderly people are:GGT 92.8%,DBil 92.8%,ALT 90.7%,AST 90.7%,TBil 86.6%,HDL 80.2%,IBil 78.4%,ALB 52.6%,Scr 50.5%,ALP 49.5%,TG 49.5%,LDL 47.3%,TC 45.4%,INR 41.2%,AFP 36.3%,PT 36.1%.By examining the above laboratory examinations can screen out the patients with liver injury with high sensitivity,but the specificity is low in the diagnosis of DILI.In addition,the increase of ALP level is not more than 10 times of the upper limit of normal value.However,the rise of ALT,AST,GGT that more than 10 times of the upper limit of normal(upper limit of normal,ULN)accounted for 26.8%,18.6%,8.2%respectively,and total bilirubin increased more than 10 times the upper limit of normal value of 42.3%.Of ALT,AST,TBiL,GGT hospital seven days down half of the cases accounted for 52.6%,39.2%,16.5%and 52.6%respectively.Between different clinical types ALT,AST,ALP,GGT and total cholesterol exist significant difference(P<0.05).(5)Imaging examination 27 cases(27.8%)showed the liver parenchyma echo change in ultrasound,5 cases(5.2%)showed the liver density change in CT,4 cases(4.1%)showed the liver MRI signal change.(6)Histological examination Histological examination is one of the most important means in the diagnosis of DILI.1 case accepted the percutaneous liver biopsy which showed nonspecific inflammation of the liver(G1S1).(7)The model for end-stage liver disease(MELD)score The MELD score of the 97 patients were between 6 to 34 points,as an average of 20.14±6.33 points.And scores between different clinical types,gender,age group had no significant difference(P>0.05).(8)Treatment and prognosis Once the diagnosis of DILI have been verified,the hepatotoxic drugs have been stopped.Medical conservative treatment including the use of reduced glutathione,polyene phosphatidyl choline and diammonium glycyrrhizinate to protect liver function.In the meanwhile give support treatment,such as proteins,plasma and the calories.Among the 19 patients accepted from 1 to 5 times of artificial liver treatment.1 cases of liver transplantation.Among the97 cases,29 cases cured,56 cases were improved,12 cases were not cured.Single factor analysis indicate different prognosis group the AST,TBiL,DBil,INR,PT,TC,WBC,GFR,Scr,hepatic failure,infection,AST and ALT dropped to half within one week and MELD score exist significant difference(P<0.05).Multivariable Logistic regression analysis showed that the AST level,ALT dropped to half within a week,total cholesterol,Scr and GFR were independent factors affecting the prognosis(P<0.05).Prediction mode for drug-induced liver failure:21 cases progressed to liver failure in 97 patients,including 13 cases of acute liver failure,8 cases of subacute liver failure.Finally,2 cases were cured,better in 11 cases,8 patients were not cured.White blood cells,INR,PT,HDL,TBil,DBil,IBil and MELD score exist significant difference between liver failure and none liver failure(P<0.05).Logistic regression analysis showed that INR and TBil are the independent risk factors to drug-induced liver failure.Conclusion:The main pathogenic drugs for DILI in the elderly is traditional Chinese medicine,next is anti-tuberculosis drugs.Clinical types of DILI in elderly people is given priority to hepatocellular injury type.Initial symptoms have no specificity.The ALT,AST level of hepatocellular injury type is significantly higher than other clinical types,and cholestasis type ALP,GGT and TC significantly higher than that of other clinical type(P<0.05).AST,TC,Scr,GFR and ALT fell to half within a week are risk factors affecting the prognosis(P<0.05).Drug induced liver injury in elderly people has a greater incidence of liver failure.INR together with TBil can predict drug-induced liver failure(P<0.05).