Treatment Response And Influence Factors Of Glucocorticoid In Severe Drug-induced Liver Injury

Objective:To investigate the effeicacy and influence factors of glucocorticoid in treatment of severe drug-induced liver injury(DILI).Methods:According to the inclusion and exclusion criteria,we collected the clinical data of 214 patients in the Department of hepatology of our hosptial who were diagnosed as severe drug-induced liver injury from October 2017 to December 2021.Patients were divided into non-steroid-treated group(n=81)and steroid-treated group(n=133),who recieved only conventional therapy and conventional therapy plus small dose of glucocorticoid in short course,respectively.Comparing the general clinical and biochemical characteristics of two groups and exploring the effeicacy,safety and influence factors of glucocorticoid treatment.The clinical efficacy was estimated by clinical symptoms and liver functional biochemical indexes of the hospitalization.Obvious efficacy was defined as the clinical symptoms significantly improved or disappeared as well as the ALT,AST and TBi L were descended more than 50% or less than 2ULN.Efficacy indicated clinical symptoms relieved,but the improvement of biochemical indexes failed to meet the level of obvious efficacy.Inefficacy meant which meet one of these criteria: 1)Could not achive the above conditions;2)Clinical symptoms and biochemical indexes continued to worsen or death;3)Patients who gave up treatment for personal reasons or transfered to a superior hospital for treatment.Result:1.The most common drugs leading to severe DILI were Chinese herbal medicine or Chinese patent medicine(70.6%),followed by combination therapy(10.7%)and non steroidal anti-inflammatory drugs(4.2%).The most common identifiable Chinese herbal ingredients are Panax notoginseng and Polygonum multiflorum.2.This study included 75 males(35%)and 139 females(65%).The sex ratio was1:1.85.The proportion of women in steroid-treated group(71%)was significantly higher than non-steroid-treated group(54%),meant women had more severe conditions tendency(P < 0.05).3.The patients in steroid-treated group had longer hospital stay(P < 0.05),lower AST level and higher TBi L and INR level(all P < 0.05),indicating steroid-treated groupg patients were more severe.4.TBi L,PT and INR in steroid-treated group decreased significantly after one week of glucocorticoid treatment,while three weeks of treatment in non-steroid-treated group(P < 0.05),indicating the glucocorticoid treatment have better restoration of serum bilirubin and improve the liver coagulation function.5.The median time for TBi L of 50% decrease in steroid-treated group and non-steroid-treated group were 6 days and 10 days,respectively(P < 0.001),indicating short-term of glucocorticoid treatment can significantly shorten the time of bilirubin restoration.6.Influence factors for glucocorticoid treatment of severe DILI(1)Clinical classification: The mixed type DILI patients had highest overall effeicacy after glucocorticoid treatment.The overall effeicacy had no significant difference between hepatocyte type and cholestatic type,which both more than 95%.(2)MELD score: The overall treatment effeicacy in steroid-treated group had no significant difference between MELD score was low-risk group and medium-risk group.For patients whose MELD score were high-risk group,the ineffective rate was highest,which up to 26.6%,P = 0.041,indicating MELD score was high-risk group patients who underwent glucocorticoid treatment had minimal benefits.(3)Time of glucocorticoid treatment: our study showed that there is no significant correlation between glucocorticoid treatment time and effeicacy,indicating patient should receive individualized treatment accoring to the response to glucocorticoid.7.The incidence of adverse reactions was 17.3% in steroid-treated group and 11.1%in non-steroid-treated group,P=0.22.Secondary infection,hypokalemia and rash were the most common adverse reactions of both group,and most of them could recovered after the supportive treatment.Some adverse reactions in steroid-treated group(such as hyperleukocytosis,hypokalemia and hyperglycemia)disappeared after stopping glucocorticoid use,indicating glucocorticoid treatment is safe.Conclusion:1.Woman took more percentage in DILI patients,and had more severe conditions tendency.2.The most common drugs leading to severe DILI were Chinese herbal medicine or Chinese patent medicine,followed by combination therapy and non steroidal anti-inflammatory drugs.The most common identifiable Chinese herbal ingredients are Panax notoginseng and Polygonum multiflorum.3.For severe DILI patients,short course of glucocorticoid treatment can significantly shorten restoration of serum bilirubin and improve the liver coagulation function with good safety.4.We recommend glucocorticoid treatment for with MELD score of low-risk group and medium-risk group.As for MELD score was high-risk group,doctors can try small dose of glucocorticoid in short course after weigh the pros and cons carefully.The patients showed poor response to glucocorticoid treatment should withdraw timely and they may benefit from artificial liver supporting treatment or liver transplantation.