Application Analysis Of Modified RUCAM Scale In Clinical Diagnosis Of Drug-induced Liver Injury

Objective:The incidence of drug-induced liver injury(DILI)is increasing year by year due to the increasing demand for drugs,the irrational use of drugs,the continuous marketing of new drugs and a series of health problems caused by environmental pollution.In 2006,the World Health Organization reported that DILI was the fifth leading cause of death in the world.The purpose of this article is to summarize the epidemiology of DILI,the types of drugs that induce DILI,clinical characteristics and diagnostic criteria,in order to deepen the understanding of the disease,so as to better diagnose DILI and guide clinical safety medication.At the same time,we explored the establishment of a modified RUCAM scale and to investigate the application of it in the diagnosis of DILI.Methods:A retrospective analysis was conducted in 129 patients diagnosed with DILI enrolled in our hospital from January 2013 to December 2018.The RUCAM score was≥6,which diagnosed as probable/highly probable DILI were analyzed for epidemiology,pathogenic drugs and clinical features.To improve the clinical diagnosis efficiency of RUCAM scale,bile acid(BA)and eosinophil%(E%)were introduced into RUCAM,the RUCAM+BA modified scale and the RUCAM+E% modified scale were established.Sixty-five DILI patients with a RUCAM score of ≥6 and 64 DILI patients with a RUCAM score of <6 were scored according to the above two modified scales.Results:1.There were 38 female patients,the average age of onset was(44.55 ±14.73)years old;27 male patients,the average age of onset was(43.89±15.88)years old.The prevalence peaks of female and male patients were 41-60 years old,accounting for 44.74%(17/38)and44.44%(12/27)respectively.2.In our country,Chinese herbal medicine/Chinese patent medicine is widely used,resulting in DILI is very common,accounting for 44.62%(29/65);other pathogenic drugs are anti-tuberculosis drugs,accounting for 18.46%(12/65);anti-cancer drugs,accounting for 9.23%(6/65);anti-hyperthyroidism drugs,accounting for 7.69%(5/65);antibiotics,accounting for 6.15%(4/65);immune inhibitor accounting for 4.62%(3/65);drug overdose and statins accounting for 3.08%(3/65),respectively;tibetan medicine and "unknown" accounted for 1.54%,respectively(1/65).3.Clinical symptoms: gastrointestinal symptoms(nausea,vomiting,anorexia,abdominal distension)are the most common,accounting for 72.31%;the other symptoms were jaundice(body skin or sclera yellow stain,yellow urine),rash and itchy skin,fatigue,fever and asymptomatic were 70.77%(46/65),23.08%(15/65),66.15%(43/65),12.31%(8/65),1.54%(1/65),respectively.4.Clinical classification: According to the type of target cells damaged,it can be divided into three types: hepatocyte injury type,cholestasis type and mixed type.Hepatocyte injury was the most common type,accounting for 83.08%(54/65);cholestasis was the second most common type,accounting for 9.23%(6/65);mixed type was the least,accounting for 7.69%(5/65).5.Serum biochemical examination: comparison between hepatocyte injury type,cholestasis type and mixed type,the peak value of ALT in hepatocyte injury type was higher than that in other two types(P<0.05);the peak value of ALP and GGT in cholestasis type were higher than that in other two types(P<0.05);there was no difference in E,E%,AST,TB and BA among the three groups(P>0.05).6.Serum immunological examination: of the DILI patients,22(44.90%)patients tested positive for ANA;a significant difference in gender was observed within this patient cohort,which included 18(81.82%)females and 4(18.18%)males(P<0.05).7.Grading of severity : 65 DILI patients with RUCAM ≥ 6 points(diagnosed as probable/highly probable DILI)were divided into two groups according to their severity levels: Group 1 was a mild group,and the study subjects were DILI patients with severity level ≤ 2(including grade 1 and grade 2);Group 2 was a severe group,and the subjects were DILI patients with severity level ≥ 3(including grade 3,grade 4,grade 5).Compare the differences in the distribution of gender(female),age,E%,ALT,AST,TB,ALP,GGT and BA between the two groups,it was found that the difference between the groups of BA was statistically significant(p<0.0001),while there was no significant difference between the groups of women,age,E%,ALT,AST,ALP,GGT(p>0.05).8.For the clinical diagnosis of DILI,the difference between the RUCAM+BA modified scale and the RUCAM scale was statistically significant(c2= 5.135,P =0.023);the difference between the RUCAM+E% modified scale and the RUCAM scale was not statistically significant(c2= 0.763,P = 0.383).Conclusion:Among patients with DILI,women and middle-aged people are more common.In our country,the drugs that cause DILI are most commonly found in Chinese herbal medicines/Chinese patent medicines,other common pathogenic drugs are anti-tuberculosis drugs,anti-tumor drugs,anti-thyroid drugs,antibiotics,etc.The main clinical manifestations are nausea,vomiting,anorexia,abdominal distension.Hepatocyte injury type is the most common type in the clinical classification of drug-induced liver injury,cholestasis type is the second,mixed type is the least.The main manifestations of hepatocyte injury type are elevated ALT,while cholestasis type is elevated ALP and GGT.Immune-mediated DILI often has similar manifestations to AIH,including positive autoimmune antibody,therefore,attention should be paid to differentiate it from AIH,especially in female patients with DILI.Bile acid can be used as a good parameter for distinguishing the severity of DILI,which is helpful for early identification of severe DILI.Compared with the RUCAM scale,the RUCAM+BA modified scale helps to improve the sensitivity of DILI diagnosis,while there is no difference in the sensitivity of DILI diagnosis between the RUCAM+E% modified scale and RUCAM scale.