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Abstract：
Background: Knowledge of metformin-induced hepatotoxicity is based on case reports. The aim of this study was to investigate the clinical features of metformin-induced hepatotoxicity. Methods: We collected relevant literature on metformin-induced hepatotoxicity published from January 1994 to February 2022 by searching Chinese and English databases. Results: Thirty patients (19 males and 11 females) from 29 articles were included, with a median age of 61 years (range 29-83). The median time to onset of liver injury was 4 weeks (range 0.3-648) after metformin administration. Clinical symptoms occurred in 28 patients, including gastrointestinal reactions (56.7%), jaundice (50.0%), fatigue (36.7%), anorexia (23.3%), pruritus (13.3%), dark urine (13.3%), and clay-colored stools (10.0%). Serum alanine transaminase, aspartate transaminase, γ-glutamyl transferase, total bilirubin and alkaline phosphatase were elevated to varying degrees. Liver imaging in 26 patients showed hepatic steatosis (6 cases, 23.1%) and gallbladder wall thickening (11.5%). Liver biopsies from 13 patients showed portal phlebitis (61.5%), cholestatic hepatitis (38.5%), and parenchymal inflammation (38.5%). After metformin discontinuation, liver function returned to normal levels at a median of 6 weeks (range 2-16). Conclusions: Metformin-induced hepatotoxicity is a rare adverse reaction. Physicians and patients should be alert to metformin-induced hepatotoxicity.
摘要：
背景：二甲双胍诱导的肝毒性的知识是基于病例报告。本研究的目的是探讨二甲双胍诱导的肝毒性的临床特征。方法:检索中英文数据库,收集1994年1月至2022年2月发表的二甲双胍肝毒性相关文献。结果:共纳入29篇文献中的30例患者(男19例,女11例),年龄中位数为61岁（范围29-83）。二甲双胍给药后，肝损伤发作的中位时间为4周（范围0.3-648）。28例患者出现临床症状,包括胃肠道反应（56.7%），黄疸（50.0%），疲劳(36.7%)，厌食症(23.3%),瘙痒（13.3%），深色尿液(13.3%),和粘土色粪便(10.0%)。血清丙氨酸转氨酶,天冬氨酸转氨酶,γ-谷氨酰转移酶，总胆红素和碱性磷酸酶均有不同程度的升高。26例患者肝脏影像学表现为肝脏脂肪变性(6例,23.1%)和胆囊壁增厚(11.5%)。13例患者的肝活检显示门脉静脉炎（61.5%），胆汁淤积性肝炎(38.5%),和实质性炎症（38.5％）。二甲双胍停药后,肝功能在中位6周（范围2-16）恢复至正常水平。结论：二甲双胍引起的肝毒性是一种罕见的不良反应。医师和患者应警惕二甲双胍引起的肝毒性。
