Clinical Study Of Drug-induced Cholestatic Liver Injury

Objective The prognosis and prognostic factors of drug-induced cholestasis liver injury have not been unified.In addition,drug-induced sclerosing cholangitis-like changes,which gets few clinical research attention,needs further in-depth study.The purpose of this paper is the following points:1.To explore the general information,underlying diseases,clinical features,medication history,blood routine and liver laboratory tests,imaging findings,severity,treatments and outcomes of cholestasis drug-induced liver injury.2.To compare the clinical characteristics of patients with different outcomes and then analyze the prognostic factors.3.To analyze the comorbidities,medication history,clinical features,laboratory results,severity and outcome of the elderly group by comparing with the young and middle-aged group.4.To investigate the proportion of sclerosing cholangitis-like changes in MRCP in patients with cholestasis drug-induced liver injury,and then to analyze the differences in clinical characteristics and prognosis between patients with and without cholangiography abnormalities.MethodsThe patients diagnosed as cholestatic drug-induced liver injury in The First Affiliated Hospital of Anhui Medical University from April 2018 to June 2022 were collected using the bidirectional cohort study.The following clinical data were recorded: age,gender,BMI,hospitalization time,smoking history,drinking history,allergy history,underlying diseases,medication history,clinical symptoms,blood routine,coagulation,initial and peak values of liver laboratory tests,viral markers,autoantibodies,MRCP changes and treatments.The follow-up time ranged from 6 months to 4 years.The data were analyzed by SPSS 25.0.Results1.There were 105 cases of cholestasis drug-induced liver injury in our hospital in the past4 years,of which 57 were males(54.3%),48 were females(45.7%).The median age was55 years,with the highest proportion of patients ≥60 years(47.0%).The main clinical symptoms were jaundice,anorexia,fatigue and abdominal distension,and few patients(12.4%)were asymptomatic.There were nearly 80 kinds of drugs involved in this study.The top three categories were traditional Chinese medicine(34.3%),antitumor drugs(22.9%)and antibiotics(10.5%).Sclerosing cholangitis-like changes were found in 7 of49 patients(14.3%)who underwent MRCP.Of the 16 patients who underwent liver biopsyies,12(75%)were cholestatic hepatitis,2(12.5%)were mixed hepatitis,and 2(12.5%)were simple cholestatic hepatitis.The proportion of grade 4 severity in these patients was highest.There were 53 patients cured(50.5%),41 improved(39.0%),7uncured(6.7%),and 4(3.8%)died.The total efficient was 89.5%.2.The R value,hemoglobin,eosinophil count,initial ALT and treatment time were significantly higher in patients with positive outcomes than those without.While,the white blood cell count were lower(P<0.05).There was no significant difference in the presence of underlying liver disease between the two groups(P=0.808).Multivariate Logistic regression analysis showed that RUCAM score[OR=0.126(0.033～0.486),P=0.003],white blood cell count[OR=1.453(1.095-1.927),P=0.010],hemoglobin[OR=0.934(0.889-0.981),P=0.006] and treatment time[OR=0.887(0.815-0.966),P=0.006] were independent predictors of prognosis in patients with cholestatic drug-induced live injury.3.There were 47 patients with age≥60 yeas.Compared with the younger group,endocrine and metabolic diseases,chronic lung disease and renal insufficiency were more common in the elderly group(P<0.05).The medication history was basically consistent between the two group,and traditional Chinese medicine was the most common.The elderly group had lower hemoglobin(P=0.001),lymphocyte percentage(P=0.021),initial value of ALT(P=0.013),peak value of ALT(P=0.015),albumin(P=0.001)and higher peak TBi L(P=0.029).In the elderly group,the severity of grade 4 was the most(40.4% vs22.4%,P=0.046).There was no significant difference in the proportion of chronic injury and the prognosis between the two groups.4.7 of the 49(14.3%)patients who underwent MRCP had sclerosing cholangitis-like changes with a median age of 54(47,60)years,including 5(71.4%)women.The illegal drugs included glibenclamide,Traditional Chinese medicine,celecoxib,ranitidine and amoxicillin.The median intake duration of medication was 20(10,30)days.The median resolution time was 138(54,251)days.Compared with non-sclerosing cholangitis group,the peak value of ALP and TBi L in sclerosing cholangitis group was higher,and the proportion of chronic injury was higher(71.4% vs 23.8%,P=0.037).Conclusion1.Drug-induced cholestasis liver injury mainly occurs in elderly patients,most of which are complicated with underlying diseases.The clinical manifestations are varied and not specific.There are many kinds of drugs involved in this disease,most of which are traditional Chinese medicines.Drug-induced cholestatic liver injury is often severe,but the overall prognosis is optimistic.2.Lower RUCAM score and hemoglobin,higher white blood cell count and shorter treatment time are independent prognostic factors of drug-induced cholestatic liver injury.3.The elderly group have many comorbidities,mainly endocrine and metabolic diseases,renal insufficiency.Compared with younger group,the elderly is more likely to have anemia,decreased albumin and severe cholestasis.4.Drug-induced sclerosing cholangitis which can be caused by a variety of drugs,are more likely to cause cholestasis and chronic liver injury.Thus,DILI should be considered as one of the differential diagnosis of cholestasis and abnormal cholangiography.