Ramachandran R, Kakar S
Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA.
J Clin Pathol. 2009 Jun;62(6):481-92. doi: 10.1136/jcp.2008.058248.
The diagnosis of drug-induced liver injury (DILI) is a challenging problem, often confounded by incomplete clinical information and the difficulty of eliciting exposure to herbal products, over-the-counter agents and toxins. The task is further rendered difficult on biopsy, as drugs can mimic all the patterns found in primary liver disease. Acute hepatitis, with or without cholestasis, is the most common histological pattern of DILI, and drugs such as acetaminophen are the leading causes of acute liver failure. Most cases of DILI resolve on discontinuation of the drug, but recovery can take months or rarely the disease can progress despite drug withdrawal. Drugs such as methotrexate can lead to chronic hepatitis and cirrhosis, while others such as minocycline, nitrofurantoin and methyldopa are implicated in autoimmune hepatitis. Prolonged cholestasis and ductopenia resembling primary chronic biliary disease can occur. Drug-induced steatohepatitis is also an uncommon pattern, but is well described with drugs such as amiodarone and irinotecan. In the presence of risk factors such as obesity and diabetes, some drugs such as tamoxifen, oestrogens and nifedipine can precipitate or exacerbate steatohepatitis. Other observed patterns include granulomatous hepatitis, vascular injury (eg, sinusoidal obstruction syndrome), Ito cell lipidosis and neoplasms (eg, adenomas).
药物性肝损伤（DILI）的诊断是一个具有挑战性的问题，常常因临床信息不完整以及难以确定是否接触过草药产品、非处方药和毒素而变得复杂。活检时该任务进一步变得困难，因为药物可模仿原发性肝病中发现的所有模式。伴有或不伴有胆汁淤积的急性肝炎是DILI最常见的组织学模式，对乙酰氨基酚等药物是急性肝衰竭的主要原因。大多数DILI病例在停用药物后可缓解，但恢复可能需要数月时间，或者极少数情况下，尽管停药，疾病仍会进展。甲氨蝶呤等药物可导致慢性肝炎和肝硬化，而米诺环素、呋喃妥因和甲基多巴等其他药物则与自身免疫性肝炎有关。可出现类似于原发性慢性胆汁性疾病的长期胆汁淤积和小胆管减少。药物性脂肪性肝炎也是一种不常见的模式，但胺碘酮和伊立替康等药物可引发该模式。在存在肥胖和糖尿病等风险因素的情况下，他莫昔芬、雌激素和硝苯地平等一些药物可引发或加重脂肪性肝炎。其他观察到的模式包括肉芽肿性肝炎、血管损伤（如窦性阻塞综合征）、伊托细胞脂质沉积症和肿瘤（如腺瘤）。
