Rangnekar A S, Fontana R J
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
Minerva Gastroenterol Dietol. 2011 Jun;57(2):213-29.
Drug induced liver injury (DILI) is an uncommon cause of acute and chronic liver injury of increasing importance to patients, clinicians, and regulators. The incidence of DILI due to an individual agent is not well defined but population-based studies suggest that the overall incidence of DILI may be as high as 10 to 15 cases per 100000 patient years. Bona fide risk factors for DILI are also not well established, but ongoing multicenter registry studies such as the Drug Induced Liver Injury Network are attempting to identify the role of genetic, environmental, and immunological factors in DILI pathogenesis and outcomes. Acute hepatocellular injury (~50%) is more common than mixed or cholestatic liver injury but jaundiced DILI subjects with either type of liver injury have a ~10% risk of short-term mortality. Antibiotics are the most commonly implicated agents associated with DILI, but there are emerging reports of liver injury associated with the use of a multitude of herbal and dietary supplements. Despite their widespread use, the HMG-CoA reductase inhibitors or statins are an uncommon cause of idiosyncratic DILI. Furthermore, recent studies have shown that statins are actually safe and efficacious to use in hyperlipidemic patients with chronic liver disease. Acetaminophen hepatotoxicity remains a leading cause of severe acute liver injury. Limiting the amount of acetaminophen in prescription narcotic products may help reduce the incidence of future non-intentional overdoses but educating patients and providers of the multitude of over the counter products that contain acetaminophen is also recommended.
药物性肝损伤(DILI)是急性和慢性肝损伤的一个不常见原因,对患者、临床医生和监管机构的重要性日益增加。单一药物所致DILI的发病率尚不清楚,但基于人群的研究表明,DILI的总体发病率可能高达每100000患者年10至15例。DILI的确切危险因素也尚未明确,但正在进行的多中心注册研究,如药物性肝损伤网络,正试图确定遗传、环境和免疫因素在DILI发病机制和转归中的作用。急性肝细胞损伤(约50%)比混合型或胆汁淤积型肝损伤更常见,但无论哪种肝损伤类型,出现黄疸的DILI患者短期死亡率约为10%。抗生素是与DILI相关的最常见药物,但越来越多的报告表明,多种草药和膳食补充剂的使用也与肝损伤有关。尽管HMG-CoA还原酶抑制剂或他汀类药物被广泛使用,但它们是特异质性DILI的不常见病因。此外,最近的研究表明,他汀类药物实际上对患有慢性肝病的高脂血症患者安全有效。对乙酰氨基酚肝毒性仍然是严重急性肝损伤的主要原因。限制处方麻醉药品中对乙酰氨基酚的含量可能有助于降低未来非故意过量用药的发生率,但也建议对患者和医疗服务提供者进行教育,使其了解众多含有对乙酰氨基酚的非处方产品。