Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity.
Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity.
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DOI：
10.18053/jctres.03.2017s1.006
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发表时间：
2017-03
期刊：
影响因子：
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通讯作者：
Fromenty B
中科院分区：
文献类型：
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作者：
Massart J;Begriche K;Moreau C;Fromenty B
背景资料：肥胖通常与非酒精性脂肪性肝病（NAFLD）相关，NAFLD是指包括脂肪肝、非酒精性脂肪性肝炎（NASH）和肝硬化在内的大范围肝脏病变。不同的研究表明或提示肥胖和NAFLD能够增加不同药物的肝毒性风险。这些药物中的一些可能会在肥胖个体中更频繁地诱发急性肝炎，而另一些可能会使预先存在的NAFLD恶化。目的：本综述的主要目的是收集关于NAFLD作为药物性肝毒性危险因素的作用的可用信息。为此，我们使用不同的查询进行了数据挖掘分析，包括药物性肝损伤（或DILI），药物性肝毒性，脂肪肝，非酒精性脂肪性肝病（或NAFLD），脂肪变性和肥胖。本文对所收集的文献中的主要数据进行了综述，并提出了一些病理生理学假设。患者相关性：可能对肥胖患者造成潜在风险的药物包括属于不同药理学类别的化合物，如对乙酰氨基酚、氟烷、甲氨蝶呤、罗格列酮、司他夫定和他莫昔芬。对于其中一些药物，在肥胖啮齿动物中的实验研究证实了临床观察结果，并揭示了不同的病理生理机制，这可以解释为什么这些药物在肥胖和NAFLD中特别具有肝毒性。其他药物，如戊巴比妥钠、苯巴比妥和奥美拉唑也可能构成风险，但需要进行更多的调查，以确定这种风险是否显著。由于肥胖者经常服用多种药物治疗不同的肥胖相关疾病，如2型糖尿病，高脂血症和冠心病，因此迫切需要确定可导致脂肪肝背景下急性肝炎或诱导NAFLD恶化的主要药物。
Background: Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including fatty liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different investigations showed or suggested that obesity and NAFLD are able to increase the risk of hepatotoxicity of different drugs. Some of these drugs could induce more frequently an acute hepatitis in obese individuals whereas others could worsen pre-existing NAFLD. Aim: The main objective of the present review was to collect the available information regarding the role of NAFLD as risk factor for drug-induced hepatotoxicity. For this purpose, we performed a data-mining analysis using different queries including drug-induced liver injury (or DILI), drug-induced hepatotoxicity, fatty liver, nonalcoholic fatty liver disease (or NAFLD), steatosis and obesity. The main data from the collected articles are reported in this review and when available, some pathophysiological hypotheses are put forward. Relevance for patients: Drugs that could pose a potential risk in obese patients include compounds belonging to different pharmacological classes such as acetaminophen, halothane, methotrexate, rosiglitazone, stavudine and tamoxifen. For some of these drugs, experimental investigations in obese rodents confirmed the clinical observations and unveiled different pathophysiological mechanisms which could explain why these pharmaceuticals are particularly hepatotoxic in obesity and NAFLD. Other drugs such as pentoxifyl-line, phenobarbital and omeprazole might also pose a risk but more investigations are required to determine whether this risk is significant or not. Because obese people often take several drugs for the treatment of different obesity-related diseases such as type 2 diabetes, hyperlipidemia and coronary heart disease, it is urgent to identify the main pharmaceuticals that can cause acute hepatitis on a fatty liver background or induce NAFLD worsening.