抗线粒体抗体M2亚型在药物性肝损伤与原发性胆汁性胆管炎患者中血清学特点分析

An analysis of the serological characteristics of anti-mitochondrial M2 subtype in patients with drug-induced liver injury and primary biliary cholangitis

目的分析抗线粒体抗体M2亚型(AMA-M2)在药物性肝损伤(DILI)和原发性胆汁性胆管炎(PBC)患者中的血清学特点,以期为临床鉴别诊断提供参考。方法回顾性收集2011年1月至2017年12月就诊的2802例DILI患者实验室资料,分析血清中AMA-M2阳性患者实验室检查特点,并将同时期就诊的120例PBC患者血清学资料作为对照。计数资料组间比较用χ^2检验,对于各组数据的丙氨酸氨基转移酶,天冬氨酸氨基转移酶,碱性磷酸酶,γ-谷氨酰转移酶,免疫球蛋白M检测结果做秩和检验,并进行单因素方差分析。结果2802例DILI患者中,AMA-M2阳性占5.1%(144/2802),其中77.1%(111/144)为单纯DILI,22.2%(32/144)为DILI合并PBC,0.7%(1/144)为DILI合并干燥综合征。单纯DILI组AMA-M2多为中、低水平,低于PBC组及DILI合并PBC组,各组比较差异均有统计学意义(P值均<0.05);DILI合并PBC组与PBC组AMA-M2水平比较,差异无统计学意义(P>0.05)。单纯DILI组和DILI合并PBC的丙氨酸氨基转移酶、天冬氨酸氨基转移酶水平分别为(585.92±653.04)U/L、(501.45±512.67)U/L和(373.47±502.60)U/L、(335.97±513.96)U/L,均显著高于PBC组[(106.33±134.08)U/L、(112.59±152.20)U/L],两组比较,差异均有统计学意义(P值均<0.05)。单纯DILI组的碱性磷酸酶水平为(152.58±81.46)U/L,低于PBC组的(237.86±215.09)U/L,两组比较,差异有统计学意义(P<0.05)。单纯DILI组的免疫球蛋白M水平为(1.76±1.16)g/L,低于PBC组[(4.74±5.74)g/L]和DILI合并PBC组(3.31±1.68)g/L,3组比较,差异有统计学意义(P<0.05)。随访单纯DILI组中,2.7%患者出现肝硬化;42.3%患者AMA-M2滴度降低,其中14.4%患者AMA-M2滴度降至正常;13.5%患者AMA-M2滴度上升,5例患者发展为PBC。结论AMA-M2并非仅见于PBC患者中,中低水平甚至高水平的AMA-M2可在DILI患者中检出。对于AMA-M2阳性的DILI患者首先需鉴别是否合并PBC;其次分析丙氨酸氨基转移酶,天冬氨酸氨基转移酶,碱性磷酸酶水平,并对患者定期随访观察,以便及早发现DILI合并PBC患者及药物诱导的PBC患者,给予及时治疗。

Objective To analyze the serological characteristics of anti-mitochondrial antibody M2 subtype (AMA-M2) in patients with drug-induced liver injury (DILI) and primary biliary cholangitis (PBC),in order to provide reference for clinical differential diagnosis.Methods Laboratory data of 2802 DILI cases who visited the hospital between January 2011 and December 2017 were retrospectively collected.AMA-M2 positive patients were analyzed with respect to laboratorical findings,and serum data of 120 patients with primary biliary cholangitis (PBC) at the same period was taken as a control.A chi-square test was used for group comparisons.One-way ANOVA and rank sum tests was used for ALT,AST,ALP,GGT and three groups of immunoglobulin M.Results Among 2802 DILI patients,AMA-M2 positive rate was 5.1%(144/2 802),77.1%(111/144) was DILI alone,22.2%(32/144) was DILI with PBC,and 0.7%(1/144) was DILI with Sjogren's syndrome.An AMA-M2 level in DILI alone group was mostly mild and moderate than the PBC group and the DILI combined with the PBC group.There was significant difference between the two groups (P < 0.05).There was no significant difference in AMA-M2 levels between DILI group combined with PBC group and PBC group (P > 0.05).ALT and AST levels of DILI alone group and DILI combined with PBC were (585.92 ± 653.04) U/L,(501.45 ± 512.67) U/L and (373.47 ± 502.60) U/L,(335.97 ± 513.96) U/L,respectively,which were significantly higher than PBC group [(106.33 + 134.08) U/L,(112.59 + 152.20) U/L].There were statistically significant differences between the two groups (P < 0.05).The ALP level of DILI alone group was (152.58 + 81.46) U/L,which was lower than PBC group (237.86 + 215.09).The difference was statistically significant (P < 0.05).The level of immunoglobulin M in the DILI alone group was (1.76 ± 1.16) g/L,which was lower than PBC group (4.74 ± 5.74) g/L and the DILI combined with the PBC group (3.31 ± 1.68) g/L.There was significant difference between the two groups.During follow-up,2.7% of patients with DILI had cirrhosis,42.3% had lower AMA-M2 titer,14.4% had lower AMA-M2 titer,13.5% had higher AMA-M2 titer and five cases developed PBC.Conclusion AMA-M2 is not only positive in patients with PBC,but also low-to-medium or even high-level AMA-M2 may be detected in DILI patients.For AMA-M2-positive DILI patients,it is necessary to identify whether they are associated with PBC.Secondly,the levels of ALT,AST and ALP should be analyzed,and the patients should be on regular follow up for early and timely detection of drug-induced PBC.