慢性药物性肝损伤患者自身抗体特征及其影响预后的因素分析

摘要/Abstract

摘要： 目的分析慢性药物性肝损伤患者自身抗体特征及其影响预后的因素。方法选择2019年3月—2022年3月赤峰学院附属医院收治的慢性DILI患者358例,在患者治疗结束后(半年后)按照预后将其分为两组,分别为预后较差(108例)与预后较好(250例)组,对所有患者自身抗体予以检测,将其分为自身抗体阳性组(145例)和自身抗体阴性组(213例),对所有患者生化治疗进行检测。结果 358例患者中,引发慢性DILI的药物种类有十几种,其中中药的占比为31.0 %,解热镇痛类药物12.3 %,抗肿瘤药物11.7%,抗生素类药物9.2 %,其次为激素类、心血管类、保健品类药物等;自身抗体检测结果显示,抗核抗体(ANA)阳性的患者占42.74%(153/358);358例慢性DILI患者中,自身抗体阳性者145例,自身抗体阴性者213例,其中自身抗体阳性组中女性占比高于阴性组,且年龄大于阴性组;预后较差患者年龄≥60岁的占比高于预后较好者,肝细胞型的患者占比低于预后较好组,胆汁淤积型或混合型高于预后较好患者,丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBil)、直接胆红素(DBil)水平分别为(519.7±90.6)U/L、(410.4±91.3)U/L、(44.0±11.8)μmol/L、(33.4±11.8)μmol/L高于预后较好组[(330.8±88.9)U/L、(269.7±80.5)U/L、(31.9±13.5)μmol/L、(27.8±9.0)μmol/L],而白蛋白(Alb)水平为(46.0±14.9)g/L,比预后较好组的(60.1±18.1)g/L低;进一步对上述指标进行分析发现,年龄≥60岁、非肝细胞型、ALT≥435.4 U/L、AST≥325.2 U/L、TBil≥38.6 μmol/L、DBil≥29.2 μmol/L,Alb≤52.2 U/L是慢性DILI预后不良的危险因素(OR=1.618、1.996、1.632、1.602、1.600、1.747、1.929,均P<0.05)。结论慢性DILI患者出现预后不良的影响因素有年龄在60岁以上、非肝细胞型、ALT≥435.4 U/L、AST≥325.2 U/L、TBil≥38.6 μmol/L、DBil≥29.2 μmol/L,Alb≤52.2 U/L,临床应对上述指标予以定期监测,并采取相应的干预措施,以改善患者预后。

关键词: 慢性药物性肝损伤, 自身抗体特征, 预后, 影响因素

Abstract: Objective To analyze the characteristics of autoantibodies in patients suffering from chronic drug-induced liver injury(DILI) and identify the key factors influencing their prognosis. Methods Between March 2019 and March 2022, 358 patients diagnosed with chronic DILI at our institution were retrospectively analyzed and categorized based on their prognosis six months post-treatment into two groups: those with a poor prognosis (108 cases) and those with a good prognosis (250 cases). Autoantibody screening was conducted for all patients, dividing them into autoantibody-positive(145 cases) and autoantibody-negative groups (213 cases). All subjects underwent biochemical therapy. Results In this cohort of 358 patients with chronic DILI, more than ten types of drugs were identified as causes, with traditional Chinese medicine being the most common (31.0%), followed by antipyretic and analgesic drugs (12.3 % ), antitumor drugs (11.7 %), antibiotics (9.2 %), and subsequently hormones, cardiovascular medications, and nutraceuticals. Autoantibody analysis revealed that 42.74 % (153/358) of patients were positive for antinuclear antibodies(ANA). Of the toatl patient cohort, 145 were found to be positive for autoantibodies while 213 were negative. It was observed that the autoantibody-postive group had a higher proportion of females and older individuals compared to the negative group. Furthermore, within the entire cohort of 358 patients, those aged ≥60 years or with non-hepatocellular types of DILI exhibited a significantly higher risk of poor prognosis. Elevated levels of alanine aminotransferase (ALT)[ (519.7±90.6) U/L vs. (330.8±88.9) U/L], aspartate aminotransferase (AST)[(410.4±91.3) U/L vs. (269.7±80.5) U/], total bilirubin (TBil)[ (44.0±11.8) μmol/L vs. (31.9±13.5) μmol/L] , direct bilirubin (DBil)[(33.4±11.8) μmol/L vs. (27.8±9.0) μmol/L] correlated with a poor prognosis, while lower slbumin (Alb) levels[(46.0±14.9) g/L vs. (60.1±18.1) g/L] were indicative of a better prognosis. Further analysis highlighted that, for the entire patient population, being aged ≥60 years, having a non-hepatocellular DILI type, and presenting with elevated ALT, AST, TBil, DBil, and decreased Alb levels were risk factors for a poor prognosis in chronic DILI (OR=1.618, 1.996, 1.632, 1.602, 1.600, 1.747, 1.929, respectively, all P<0.05). Conclusion Identified risk factors for poor prognosis in patients with chronic DILI include being over 60 years of age, having a non-hepatocellular type, and presenting with elevated biochemical markers such as ALT levels≥435.4 U/L, AST levels≥325.2 U/L, TBil levels≥38.6 μmol/L, DBil levels≥29.2 μmol/L, and reduced Alb levels≤52.2 U/L. Given these findings, regular monitoring of these indicators is imperative, Implementing corresponding intervention measures based on these parameters is crucial for enhaning patient outcomes and improving prognosis.

Key words: Chronic drug-induced liver injury, Autoantibody characteristics, Prognosis, Influencing factor

马文军, 曲相珍, 周静亚, 马维娜, 李宏韬. 慢性药物性肝损伤患者自身抗体特征及其影响预后的因素分析[J]. 肝脏, 2024, 29(4): 453-456.

MA Wen-jun, QU Xiang-zhen, ZHOU Jing-ya, MA Wei-na, Li Hong-tao. Analysis of autoantibody characteristics and prognostic factors in patients with chronic drug-induced liver injury[J]. Chinese Hepatolgy, 2024, 29(4): 453-456.

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