In nearly 50% of patients with drug-induced liver injury, the bile flow is impaired known as cholestasis. Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease that happens in pregnancy. Some of the clinical symptoms include pruritus, dark urine, and abnormal liver function tests. A rise of serum bile acids is the most accurate diagnostic evidence. ICP may lead to premature birth, fetal distress, and even postpartum hemorrhage or stillbirth in some severe cases. Higher bile acid levels (> 40 μmol/L) are associated with higher rates of adverse fetal outcomes. Due to the multifactorial nature of ICP, its etiology is still not fully understood. Therefore, the current treatments of ICP are limited to control symptoms and protect fetuses. Among various causing factors, drug exposure during pregnancy is one common factor, and it can be prevented if we know drugs with increasing risk of cholestasis. Here we analyzed over 9.5 million FDA adverse effect reports to identify drugs with increasing risks of cholestasis as an adverse effect. Patients treated for cholestasis or liver diseases were removed. The odds ratio analysis reveals that lansoprazole (LSPZ), omeprazole (OMPZ) and amoxicillin (AMXC) are associated with an increased risk of cholestasis. LSPZ is associated with increased reported cholestasis by a factor of 2.32 (OR with 95% confidence interval [2.21, 2.43]). OMPZ is associated with increased reported cholestasis by a factor of 2.61 [2.54, 2.69]. AMXC is associated with increased reported cholestasis adverse effect by a factor of 6.79 [6.49, 7.11]. The risk of cholestasis associated with these three drugs is further increased in pregnant women. These findings justify careful reassessment of the safety of the three identified drugs.

中文翻译：

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人口规模回顾性分析揭示了服用奥美拉唑，兰索拉唑和阿莫西林的孕妇胆汁淤积的潜在风险。

在近50％的药物性肝损伤患者中，称为胆汁淤积的胆汁流量受损。妊娠肝内胆汁淤积症（ICP）是妊娠中最常见的肝病。一些临床症状包括瘙痒，尿黑和肝功能异常。血清胆汁酸升高是最准确的诊断依据。在某些严重的情况下，ICP可能导致早产，胎儿窘迫，甚至产后出血或死产。较高的胆汁酸水平（> 40μmol/ L）与较高的胎儿不良结局发生率相关。由于ICP的多因素性质，其病因仍未完全了解。因此，目前的ICP治疗仅限于控制症状和保护胎儿。在各种原因中，怀孕期间的药物暴露是一种常见因素，如果我们知道胆汁淤积风险增加的药物，就可以预防。在这里，我们分析了超过950万份FDA不良反应报告，以鉴定出胆汁淤积风险增加的药物为不良反应。治疗胆汁淤积或肝病的患者被移除。优势比分析显示，兰索拉唑（LSPZ），奥美拉唑（OMPZ）和阿莫西林（AMXC）与胆汁淤积的风险增加相关。LSPZ与报告的胆汁淤积增加相关的因素是2.32（OR为95％置信区间[2.21、2.43]）。OMPZ与报告的胆汁淤积增加相关的因素是2.61 [2.54，2.69]。AMXC与报告的胆汁淤积性不良反应增加了6.79倍[6.49，7.11]。与这三种药物相关的胆汁淤积的风险在孕妇中进一步增加。