Efficacy Of Glucocorticoid And Non-bioartificial Liver Support System In The Treatment Of Patients With Drug-induced Liver Disease

【Background】Drug-induced liver injury(DILI)refers to the injury of liver cells or the decrease of liver function caused by various prescriptions or over-the-counter chemical drugs,traditional Chinese medicine,natural medicine,health care products,dietary supplements,metabolic products and even accessories.It is one of the most common and serious adverse drug reactions,which can lead to acute liver failure and even death.The incidence of drug-induced liver disease(DILD)is also increasing year by year while new drugs are being developed and applied in clinic.Liver is the main organ of drug metabolism,it is also the main target organ of drug injury,and its damage mechanism has not been fully elucidated so far.The mechanism of drug-induced liver injury can be summarized as the direct toxicity and the destructive effect of drugs on hepatocytes.For various clinical manifestations and different levels of development of drug-induced liver disease patients,the treatments are not constant,and the treatment effect varies from person to person.Glucocorticoid and non-bioartificial liver support system(NBLS)therapy,as a special treatment for liver diseases,has accumulated some experience in the treatment of a large number of clinical patients.Glucocorticoid(GC)is a steroid hormone secreted by a bundle in the adrenal cortex,which regulates the biosynthesis and metabolism of sugars,fats and proteins,and inhibits immune response,anti-inflammatory,antiviral,and shock effects.Among them,the middle effect hormone is the least side effect and the only long-term application of the hormone,long-term use of high safety,has been used in drug-induced liver disease clinical treatment.There have been a number of retrospective studies on the treatment of drug-induced liver disease by glucocorticoid,which shows that glucocorticoid has a good effect on the treatment of cholestasis drug-induced liver disease.non-bioartificial liver support system is a physical or mechanical method by means of chemical treatment of blood purification technology,through the temporary replacement of the liver function of the device to play a role in purifying the environment,so that the liver cells to restore regeneration,remission of disease.Non-bioartificial liver support system treatment mode includes plasma exchange(PE),blood or plasma bilirubin,ammonia and drug hemoperfusion/plasma adsorption(DHP/PA),hemoperfusion(HP)and other treatment methods.Through the combination of different treatment modes,the treatment of non-bioartificial liver support system can significantly improve the liver function and general state of liver failure patient,reduce mortality.In China,it is mainly used for patients caused by acute,subacute liver failure,hyperbilirubinemia treatment.The types of drug-induced liver injury and the mechanism of liver disease are different in clinical manifestations of drug-induced liver disease.According to the time of the disease,the clinical characteristics and the degree of disease have acute and chronic,the prognosis of the development is also different.The type of drug cover that may cause liver damage is very wide and versatile,resulting in a variety of factors,mild only physical discomfort,severe or even liver failure and inducing malignancy.Therefore,the treatment of drug-induced liver disease does not have a unified treatment model,according to the existing treatment experience to explore different and even individualized treatment for today’s drug-induced liver disease patients are particularly important treatment.【Objective】1.To observe the efficacy and safety of individual or combined therapy of glucocorticoid or non-bioartificial liver support system in patients with drug-induced liver disease on the basis of routine drug therapy.2.To explore the factors that may affect the choice of treatment options for patients with DILD,so as to provide clinicians with a reference for decision-making in treatment.3.To explore the factors that may affect the therapeutic effectiveness of patients with DILD in order to provide more appropriate treatment for the patient and to provide better treatment decisions for clinicians.【Methods】To retrospectively collect the information of the patients hospitalized with DILD from January 2012 to June 2017 in the Department of digestion internal medicine of Xijing hospital,and all the patients collected were eligible for the inclusion criteria.According to the treatment methods used during hospitalization,patients were divided into glucocorticoid treatment group,non-bioartificial liver treatment group,combination treatment group and conventional treatment group.The efficacy and safety of the treatment were observed by comparing the changes of biochemical indexes and clinical symptoms before and after treatment.After matching by the propensity score matching method,the effect of non-biological artificial liver treatment on the treatment effect of patients with DILD was evaluated.Non-conditional logistic regression single factor and multifactor analysis were carried out to select the independent factors which could be used for reference in the related baseline indexes which affect the choice of patients ’ treatment and treatment effect.【Results】1.In this study,172 patients hospitalized with DILD were collected,including 23 patients in glucocorticoid treatment group,27 patients with non-bioartificial liver treatment group,15 cases in combined treatment group and 107 cases in routine treatment group.Among them,glucocorticoid treatment Group 2 cases ineffective treatment,non-bioartificial liver treatment Group 5 ineffective,combined treatment Group 2 cases ineffective,the general treatment group all effective.2.The statistics showed that the levels of ALT,AST,TBiL,DBil,TBA in each group were significantly decreased,and the difference was statistically significant(P<0.05)and the clinical symptoms were significantly improved.The level of WBC in the glucocorticoid treatment group and the combined treatment group increased,the level of HGB decreased,which was statistically significant compared to before treatment(P<0.05),and there was no significant change in the level of ALB and INR after treatment in the non-bioartificial liver treatment group,the combined treatment group and the conventional treatment group(P>0.05).3.The propensity score matching method was used to match the baseline level between the non-biological artificial liver treatment group and the non-use treatment group.After the comparison,the two groups of patients after the treatment related laboratory test indicators found that the non-biological artificial liver was not used.Compared with the treated patients,the white blood cells,hemoglobin,liver function alanine aminotransferase,aspartate aminotransferase,total bilirubin,direct bilirubin,glutamyl transpeptidase and other indicators were significantly different in the treated group.The difference was statistically significant(P<0.05).There was no statistical difference between the prothrombin activity and the international normalized ratio,which reflected the coagulation status(P>0.05).4.According to the treatment of patients,the treatment of patients with corticosteroids,non-bioartificial liver therapy and combination therapy for special combined treatment group,and the rest patients only using conventional medical therapy to conventional treatment group.Patients with a number of related baseline indicators as independent variables,whether to take special treatment as the dependent variable(dichotomous variable),non-conditional Logistic regression univariate and multivariate analysis,multivariate analysis showed: TBiL(OR: 21.478;95 % CI: 4.155-111.039;P<0.001)and AST(OR: 17.493;95% CI: 1.752-174.667;P=0.015)are independent factors influencing the use of special treatment in DILD patients;whether a patient to take glucocorticoids treatment as a dependent variable(dichotomous variable),non-conditional logistic regression multivariate results showed: AST(OR:4.638;95%CI:1.419-15.158;P=0.011)are independent factors that affect the way in which glucocorticoid therapy is taken in patients with DILD.5.Taking patients with a number of related baseline indexes as independent variables,taking the therapeutic effect as "effective" or "ineffective" as the dependent variable(dichotomous variable),the non-conditional logistic regression single factor and multifactor analysis were performed,and the multifactor results showed that TBiL(OR:0.085;95%CI:0.010-0.691;P=0.021)and PTA(OR: 0.092;95%CI: 0.015-0.562;P= 0.010)are independent factors affecting the therapeutic efficacy of DILD patients.【Conclusion】1.On the basis of conventional drug therapy,the addition of glucocorticoids and non-biological artificial liver alone or in combination can reduce the level of ALT,AST,TBiL,DBil and TBA in DILD patients,and the overall efficacy is positive and the safety is high.After treatment with glucocorticoids,it has a greater impact on various biochemical indicators of patients.It is recommended that the indications should be strictly controlled when using glucocorticoids,and it can be considered as a second-line treatment plan when conventional drug treatment is not effective.2.Non-biological artificial liver treatment can significantly improve the liver-related laboratory test indicators of patients with DILD,but has no effect on the blood coagulation status of patients.The treatment method is more targeted to the liver and is a more favorable treatment for patients with severe DILD.3.TBiL and AST are independent factors influencing the use of special treatment in DILD patients;DBi L,AST and MELD score are independent factors that affect the way in which glucocorticoid therapy is taken in patients with DILD.4.TBiL and PTA are independent factors affecting the therapeutic efficacy of DILD patients.