| Objective:Ankylosing Spondylitis(AS) was a chronicly processive disease which mainly occured in young men. It had a close relationship with HLA-B27 and inflammation of attachment point was its pathogenic character.It was realized gradually that using disease modifying antirheumatic drugs(DMARDs) earlier and properly could effectively alleviate symtoms and prevent patients from joints informity. DMARDs acted slowly and still had effection long after stoping administering. The mechanism of action of DMARDs was to inhabit the synthesis of large biological molecular.Literature reports confirmed that some DMARDs had certain curative effect,such as sulfasalazine(SASZ),methotrexate(MTX), leflunomide(LEF).Liver damage was DMARDs'major adverse reaction. At the same time ,it was still controversial that folic acid may alleviate the side effects of MTX.The aim of this paper was to probe into short-term liver damage of different DMARDs in AS patients and the effection of folic acid in liver function,so as to provide certain basis in establishing treatment theme according to ratio/effect ratio for the clinicians.Methods:All of the ankylosing spondylitis cases were chosen from inpatients in the Department of Immunology and Rheumatology inThird hospital of Hebei Medical University, during January 2008 to July 2010. They were all corresponded the modified New York criteria for AS. Patients admitted had to be as follows:initial treatment or hadn't take DMARDs in the last month,taking medicine and returning visit regularly, liver function was nomal.At the same time, patientswith serious heart disease,hypertension,peptic alcer,HbsAg(+),pregnant and lactation women,other organic diseases and liver diseases before were excluded.The objects were divided into MTX group,LEF group,SASP group and had been dealt with separately: MTX group MTX 10mg 1/w;LEF group LEF10mg 1/d,SASP group SASP1.0 2/d. The liver function were detected at baseline,half a month,3months and 6 months. liver function indexes included ALT(5～40U/L), AST(10～40U/L), BIL(3.0～20.0umol/L), ALP(15～130U/L),γ-GT(7～40 U/L),TBA(1.0～10.0umol/L), CHE(5～12KU/L), LDH(76～200U/L).It was diagnosed drug-induced liver injury in case of ALT≥2ULN or BIL≥2ULN.And drug-induced liver injury was dividide into three types(hepatocyte injury type, Cholestasis type and mixed type) according to the international consensus proposal published in 1990.SPSS18.0 was used to process all data. Expression of measurement data used (x|-)±s,comparation of rates used chi-square test,means of diffenent groups used vatiance analysis.P value of < 0.05 was considered significant.Results:1 Description of general informaion:197 patients in all were admitted,including 17 women and 180 men;The average age was (25.23±8.56) years, with a mean disease duration of (5.35±5.02) years. Patients with pains or swelling of peripheral joints were 156(79.19%).All patients coadministrated one kind of NSAIDs(meloxicam or diclofenac sodium or nimesulide),one or two kinds of chinese patent medicine.Some patients also took anti-osteoporotic drugs. There were no differences in different DMARDs'groups in age, gender, disease duration,alcohol concumption and whether used prednison or not(P>0.1).2 Drug-induced liver injury information in the three groups:Liver function indexes were rechecked at half amonth(mean 14±3d),the third month(mean 62±9d),the sixth month(mean 168±32d) after taking DMARDs.The incidence rates of different groups were as follows: MTX group(8/62), SASP group(5/78)and LEF group(10/57).There were no statistical differences(P>0.05).According to the international consensus proposal published in 1990:17 patients belonged to hepatocyte injury type(6 in MTX group,3 in SASP group,8 in LEF group), and no statistical differences among the three groups(P>0.05),3 belonged to cholestasis type(1 in MTX group,the other 2 in SASP group) and 3 belonged to mixed type(1 in MTX group,the other 2 in LEF group).Because the numbers in cholestasis type and mixed type were too few, differences among the groups were not compared.3 variance information of total liver functin indexes of drug-induced liver injury:All of the 23 drug-induced liver injury cases were accompanied by abnormality of ALT(109.09±17.65)U/L,and some abnormality of other indexes at variable degrees. There were no differences among the elevation levels of ALT in the different DMARDs'groups(P>0.05).4 Times happening liver injury:Numbers of liver injury at half a month, the third month and the sixth month were separately as follows: MTX group:2,5,1 ; SASP group:0,3,2; LEF group:2,5,3. There were significant differences among the three different time points(P=0.013). 56.52% of patients happened at the third month'rechecking time point.5 folic acid information in group MTX:The rate of liver injury was 2/19 in patiens who took MTX and folic acid at the same time,and rate was 6/43 in patients who took MTX without folic acid.There was no difference between them(P>0.05).But there was difference (P=0.031)between patients coadministrated folic acid(3/19)and patients who did not take folic acid(19/43).Conclusion:1 Taking MTX ,SASP or LEF for ankylosing spondylitis patients might cause liver injury.And there were no significant difference in the rates among the different DMARDs groups in 6 month.It was necessary to carry out large sample and long-term follow-up observation to illustrate the safety of DMARDs.2 The abnormal indexes of liver function mainly presented as elevation of ALT,so ALT was a sensitive one.The type of DMARDs'induced liver injury was hepatocyte injury type,the other 2 types were rare. 3 Observation for 6 months,drug-induced liver injury by DMARDs mainly happened in half a month to three months after drugs taken.It was necessary to monitor liver function for patients whose function indexes were normal when rechecking at half a month.4 Coadministrating folic acid and MTX did not reduce rate of liver injury in short term,but it could reduce the abnormality rate of ALT,which might imply that folic acid could protect liver at a certain degree.
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