二甲双胍致药物性肝损伤罕见一例并文献复习

A Rare Case of Drug-Induced Liver Injury Due to Metformin and Literature Review

摘要: 二甲双胍是治疗2型糖尿病的一线口服药物，其临床安全性和耐受性普遍良好，但诱发严重肝毒性的情况极为罕见。本文报道1例62岁女性患者，因“间断右上腹疼痛伴皮肤及巩膜黄染2月”入院。患者有半年2型糖尿病病史，长期规律服用二甲双胍治疗(具体剂量不详)，血糖控制尚可。入院检查显示肝功能显著异常：ALT 1223U/L、AST 666U/L、总胆红素99.4 μmol/L、直接胆红素60 μmol/L。影像学检查排除胆道梗阻及占位性病变，肝穿刺活检提示肝细胞弥漫性水肿、坏死及炎症细胞浸润，符合药物性肝损伤(DILI)特征。根据ALT/ALP (R值 = 3.91)，本例属于混合型偏肝细胞型DILI。结合RUCAM评分10分(极可能)，排除病毒性、自身免疫性肝病等其他病因后，确诊为二甲双胍所致DILI。停用二甲双胍并给予保肝治疗2周后，患者症状缓解，肝功能逐步改善。值得注意的是，随访期间患者因糖尿病再次使用口服降糖药时，肝功能短期内再次异常，提示肝脏对药物存在高度敏感性。本病例提示，临床使用二甲双胍时需密切监测肝功能，一旦出现肝损伤相关症状应及时停药并明确病因，早期识别和干预对改善预后至关重要。

Abstract: Metformin is the first-line oral drug for the treatment of type 2 diabetes mellitus, and its clinical safety and tolerability are generally good, but the incidence of severe hepatotoxicity is extremely rare. In this article, we report a case of a 62-year-old female patient who was admitted to the hospital with “intermittent right upper abdominal pain with yellowing of the skin and sclera for 2 months”. The patient had a six-month history of type 2 diabetes mellitus and had been taking metformin regularly for a long period of time (the exact dosage was not known), and her glycemic control was fair. Admission tests showed significant abnormalities in liver function: ALT 1223 U/L, AST 666 U/L, total bilirubin 99.4 μmol/L, direct bilirubin 60 μmol/L. Imaging studies excluded biliary obstruction and space-occupying lesions, and a liver puncture biopsy showed diffuse edema, necrosis, and inflammatory cell infiltration in hepatocytes, which was consistent with the features of drug-induced liver injury (DILI). According to ALT/ALP (R value = 3.91), this case belonged to mixed partial hepatocellular DILI. Combined with the RUCAM score of 10 (highly probable), the diagnosis of metformin-induced DILI was confirmed after ruling out other etiologies, such as viral and autoimmune liver diseases. After discontinuing metformin and giving hepatoprotective therapy for 2 weeks, the patient’s symptoms were relieved, and her liver function gradually improved. Notably, when the patient was reintroduced to oral hypoglycemic agents for diabetes mellitus during the follow-up period, the liver function became abnormal again in a short period of time, suggesting that there is a high degree of sensitivity of the liver to the drug. This case suggests that liver function should be closely monitored when metformin is used in clinical practice, and once symptoms related to liver injury appear, the drug should be stopped and the etiology of the disease should be clarified, and early identification and intervention are crucial for improving the prognosis.