College of Pharmacy, Ohio State University, 500 West 12th Ave., Columbus, OH 43210, USA.
J Am Pharm Assoc (2003). 2010 May-Jun;50(3):407-10. doi: 10.1331/JAPhA.2010.08090.
To explore why some clinicians hesitate to use metformin in patients with liver disease and whether routine monitoring of transaminases before and during metformin therapy is substantiated.
A Medline literature search was conducted (1966 to June 2008) using the terms metformin, lactic acidosis, liver disease, chronic liver disease, hepatotoxicity, hypoxia, risks, and predisposing factors.
Manufacturer prescribing information and some current medical and lay press literature caution against metformin use in patients with liver disease. This recommendation is interpreted variably by different prescribers, with some believing that the caution implies metformin can cause or worsen liver injury. Others believe that liver disease predisposes patients to developing lactic acidosis. A clearer understanding of how and when to screen for liver dysfunction in patients before and during metformin therapy is thus warranted.
Metformin does not appear to cause or exacerbate liver injury and, indeed, is often beneficial in patients with nonalcoholic fatty liver disease. Nonalcoholic fatty liver frequently presents with transaminase elevations but should not be considered a contraindication to metformin use. Literature evidence of liver disease being associated with metformin-associated metabolic acidosis is largely represented by case reports. Most such patients had cirrhosis and were also actively using alcohol. Patients with cirrhosis, particularly those with encephalopathy, may have arterial hypoxemia, which heightens the risk of developing lactic acidosis. For this reason, identifying patients with cirrhosis before initiating metformin seems prudent. Because cirrhosis can exist in the face of normal liver transaminases, however, and because metformin is not considered intrinsically hepatotoxic, withholding metformin from patients with abnormal transaminases or routinely monitoring transaminases before or during metformin treatment is not supported.
探讨为何一些临床医生在肝病患者中不愿使用二甲双胍，以及在二甲双胍治疗前后常规监测转氨酶是否有依据。
对医学文献资料进行了 Medline 文献检索（1966 年至 2008 年 6 月），检索词包括二甲双胍、乳酸酸中毒、肝病、慢性肝病、肝毒性、缺氧、风险和诱发因素。
生产商的说明书及一些当前的医学和通俗文献告诫肝病患者禁用二甲双胍。不同的医生对这一建议有不同的解读，有些医生认为这意味着二甲双胍会导致或加重肝损伤；而有些医生则认为肝病使患者易发生乳酸酸中毒。因此，更清晰地了解如何以及何时在开始二甲双胍治疗前和治疗期间对患者进行肝功能筛查是有必要的。
二甲双胍似乎不会导致或加重肝损伤，事实上，它对非酒精性脂肪性肝病患者通常是有益的。非酒精性脂肪性肝病常伴有转氨酶升高，但不应将其视为使用二甲双胍的禁忌证。有关肝病与二甲双胍相关代谢性酸中毒相关的文献证据主要来自病例报告。这些患者多数有肝硬化，且同时还在大量饮酒。肝硬化患者，尤其是伴脑病者，可能存在动脉低氧血症，这会增加发生乳酸酸中毒的风险。出于这个原因，在开始使用二甲双胍之前识别出肝硬化患者似乎是明智的。然而，由于肝硬化可能在正常的肝转氨酶情况下存在，并且由于二甲双胍不被认为具有内在的肝毒性，因此不能因为患者的转氨酶异常而拒绝为其使用二甲双胍，或常规在开始或继续二甲双胍治疗前监测转氨酶。
