The Clinical Characteristics Of 190 Patients With Drug-Induced Liver Injury And The Correlation Between Serum ?-L-Fucosidase And Drug-Induced Liver Injury

Objective: Serum Alpha-l-Fucosidase(AFU)is a lysosomal acid hydrolytic enzyme that catalyzes the glycosylase oligosaccharides,glycoproteins,glycolipids and other macromolecules in human body,which has been proved to be a specific marker for the early diagnosis of primary liver cancer.Relevant studies have shown that AFU is also associated with viral hepatitis and non-alcoholic fatty liver disease.At present,there is no related research on AFU and DILI at domestic and overseas.This study firstly analyzed the clinical characteristics of the included 190 patients with DILI,and the first time to explored the correlation between AFU and DILI,to evaluate whether it can be used to assess the severity of DILI patients' disease and predict their prognosis.Methods: This is a retrospective study,there were 190 patients diagnosed with drug-induced liver injury in our hospital from January 2016 to September 2019 were collected,including 80 males and 110 females,with an average age of(53.85±14.37)years.This study was divided into two parts.The first part analyzed the general clinical characteristics of DILI patients,and the second part divided DILI patients into low AFU group(AFU<48U/L)and high AFU group(AFU?48U/L)according to the median level of AFU.Consulted the clinical case data of the patients during hospitalization,Collected the basic information of the patients(age,gender),past medical history(hypertension,diabetes,coronary heart disease,stroke,rheumatism,hyperthyroidism,epilepsy,TB),smoking history,drinking history,drug urgent priorities,cause liver damage,the administration way,clinical manifestation,auxiliaryexamination,(liver function,consulted oagulation routine,consulted imaging examination,consulted histopathological examination of the liver),drug-induced liver injury clinical classification(liver cell type,cholestasis type,mixed type),degree of drug induced liver injury(grade 1 mild,2 moderate l,3 severe,4 acute liver failure,5deadly),treatment and outcome(death,invalid,improvement,cure).The study end point was the occurrence of nosocomial endpoint events in DILI patients,including liver failure,ineffective discharge or transfer,and death.Consulted SPSS 22.0statistical software was used for statistical analysis to analyze the clinical characteristics of DILI patients and compared the clinical data of the low AFU group and the high AFU group.Odds ratio(OR)and 95% Confidence interval(CI)were calculated by binary Logistic regression analysis.At the same time,the Receiver operating characteristic(ROC)curves of AFU for nosocomial liver failure and endpoint events in DILI patients were analyzed.Results:1.Analysis of clinical characteristics of DILI patients1.1 The average age of the 190 patients with DILI was(53.85±14.37)years old,mainly ranging from 41 to 85 years old.There were 66 patients with basic diseases,accounting for 34.7%.Among them,55(28.9%)and 11(5.8%)were the most patients with hypertension and diabetes.There were 54 long-term smokers(28.4%)and 19 long-term drinkers(10%).1.2 The first four drugs causing liver injury were 72 cases of traditional Chinese medicine(37.9%),20 cases of radix notoginseng(10.5%),18 cases of proprietary Chinese medicine(9.5%)and 16 cases of antibiotics(8.4%),most of which were taken orally,mainly causing hepatocellular liver injury(P<0.05).The intrahepatic clinical manifestations of DILI patients were mainly belching,nausea and vomiting,insufflation and fatigue,yellow eyes and yellow urine,etc.while the extrahepatic clinical manifestations were mainly skin yellowing accompanied by itching,fever,chills,dizziness,headache,rash,palpitation and chest tightness.A few patients did not have the above symptoms.1.3 Abdominal ultrasound examination was performed in 128 patients(67.4%),and the main manifestations were liver echo thickening,liver cyst,gallbladder wall thickening,cholecystitis,etc.Abdominal CT examination was performed in 63patients(33.2%),and the main manifestations were hepatic cyst,cholecystitis,and mild fatty liver.32 patients(16.8%)underwent abdominal MRI,which was similar to CT.1.4 Most of the patients were treated with drug combination,and the median length of hospitalization was 10.5 days.Among them,186 cases(97.9%)were improved or cured,12 cases(6.3%)were liver failure,3 cases(1.6%)were invalid discharged or transferred to hospital,and 1 case(0.5%)was dead.2.Comparison of clinical data of DILI patients with low AFU group and high AFU group2.1 Compared with the low AFU group,the patients in the high AFU group had longer hospital stay and higher admission requirements of AFU,bilirubin,alkaline phosphatase,glutamyl transferase and activated partial thrombin.At the same time,more patients developed liver injury of grade 3 or above,and more patients were treated with cholagogic and liver protective drugs(P<0.05)2.2 The incidence of liver failure and the endpoint of high AFU group patients was more,the incidence of liver failure was 5.471 times higher in the high AFU group than in the low AFU group(adjusted OR=5.320,95% CI 1.114 25.398,P=0.036),suggesting that high AFU was an independent risk factors for hepatic failure occurred in the institute,while women,age ? 60 years,acute course of the disease,hepatocellular liver injury were not independent risk factors for nosocomial liver failure.The incidence of nosocomial endpoint events was 6.723 times higher in the high AFU group than in the low AFU group(adjusted OR=6.321,95%CI1.349-29.621,P=0.019),suggesting that high AFU was an independent risk factor for nosocomial endpoint events in DILI patients.Meanwhile,age?60 years was also an independent risk factor for nosocomial endpoint events in DILI patients(OR=3.230,95%CI 1.003-10.399,P=0.049),while female,acute course of disease and hepatocellular liver injury were not independent risk factors for nosocomial endpoint events.2.3 The ROC curve of AFU for nosocomial liver failure in DILI patients was analyzed,and the AFU-AUC value was 0.691(95%CI 0.62-0.755,P=0.003),which had certain predictive value.The AFU critical value was 52.8U/L,the sensitivity was75.0%,and the specificity was 62.9%.The ROC curve of AFU for nosocomial endpoint events in DILI patients was analyzed,and the AFU-AUC value was 0.702(95%CI 0.632-0.766,P<0.001),which had certain predictive value.The AFU critical value was 52.8U/L,the sensitivity was 78.6%,and the specificity was 63.6%.Conclusions:Most patients with DILI were acute onset,and the majority of them were female,middle-aged and elderly.Most of them were oral medication,and the pathogenic drugs were mainly traditional Chinese medicine.The clinical manifestations of DILI patients were mainly gastrointestinal symptoms and hepatocellular liver injury,and the vast majority of patients could be improved or cured after drug withdrawal and normal treatment.Patients in the high AFU group were more seriously ill,and high AFU was an independent risk factor for nosocomial liver failure and endpoint events in DILI patients.The AFU critical value of nosocomial liver failure and endpoint events in DILI patients was 52.8U/L,which may be a new method to evaluate the condition and predict the prognosis of DILI patients.