Characteristics And Risk Factors Of First Line Anti-tuberculosis Drug Induced Liver Injury

BackgroundIsoniazid,rifampicin,pyrazinamide,and ethambutol are currently the first-line drugs recommended for the treatment of tuberculosis.The principle is early,regular,full course,appropriate,and combined use of several first anti-tuberculosis drugs.Drug-induced liver injury is a common adverse reaction to anti-tuberculosis drugs,which can lead to interruption of treatment,acute liver failure and even death.In order to prevent Anti-tuberculosis drug-induced liver injury(ATLI),it is of great significance to explore the clinical characteristics and analyze risk factors of these patients.ObjectiveTo describe the incidence of liver injury caused by first line anti-tuberculosis drugs,analyze patient characteristics,explore related risk factors,and investigate ATLI incidence changes over time,in order to provide more experience for the prevention and management of liver injury caused by first line anti-tuberculosis drugs in the future.MethodA analysis of the data of 572 patients with active pulmonary tuberculosis who underwent inpatient routine anti-tuberculosis treatment was conducted at the First Affiliated Hospital of Xinxiang Medical University from August 2016 to August 2019.Patients’ baseline liver function was normal.Observe the use of first-line anti-tuberculosis liver injury occurred within 6 months after the drug.We recorded the time of liver injury,the type of liver injury,serological indicators,the composition of anti-tuberculosis programs,and the use of liver protection drugs.Then we used the time-dependent COX regression model to analyze the independent risk factors leading to liver injury.ResultDuring the follow-up period,the incidence of ATLI was 11.7%(67 cases),of which 72% of ATLI cases occurred in the first 2 months after starting treatment.Compared with patients without liver injury,patients with ATLI were older,with a higher proportion of drinking history,a higher proportion of autoimmune diseases,a higher proportion of respiratory symptoms as the first symptom,more proportion of Hepatitis B virus(HBV)and Hepatitis C virus(HCV)infection,as well as lower proportion of patients with cavities in the lungs.Analyzing the characteristics of patients with abnormal liver function in baseline demonstrated that the most used anti-tuberculosis treatment was the HRZE,and the majority patients(99%)had used liver protection drugs.Most patients had obvious symptoms of liver function impairment(87%),and a small number of patients was lack of obvious symptoms.The proportions of patients with mild,moderate,and toxic liver dysfunction were 42%,30%,and 28%,respectively.The types of anti-tuberculosis drug induced liver injury included 31 cases of hepatocyte injury type,14 cases of cholestasis type,and 22 cases of mixed type.Among the four first-line anti-tuberculosis drugs,pyrazinamide had an average of 3.02 liver damages per 100 people per month,making it the most toxic first-line anti-tuberculosis drug.Time-dependent COX regression showed that the risk of liver injury induced by pyrazinamide,isoniazid,and rifampicin increased with treatment time.In addition to drug factors,gender,age,previous drinking history,HBV infection,and HCV infection were also independent risk factors for anti-tuberculosis drug induced liver injury.ConclusionThe incidence of first-line anti-tuberculosis drug induced liver injury caused in Henan Province is consistent with other studies conducted in China.Pyrazinamide is the most toxic first-line anti-tuberculosis drug in the liver,and the risk of liver injury caused by anti-tuberculosis drugs increases with the extension of treatment.Therefore,prior using first-line anti-tuberculosis treatment,especially before using a pyrazinamide-containing treatment regimen,the patient’s risks should be carefully assessed,and the liver function changes of the patient should be intensively monitored during first 2 months after beginning treatment.