The Disease-Modifying Therapies of Relapsing-Remitting Multiple Sclerosis and Liver Injury: A Narrative Review.
The Disease-Modifying Therapies of Relapsing-Remitting Multiple Sclerosis and Liver Injury: A Narrative Review.
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DOI：
10.1007/s40263-021-00842-9
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发表时间：
2021-08
期刊：
影响因子：
6
通讯作者：
Grieco A
中科院分区：
文献类型：
--
作者：
Biolato M;Bianco A;Lucchini M;Gasbarrini A;Mirabella M;Grieco A
在这篇叙述性综述中，我们分析了所有可用于治疗复发缓解型多发性硬化症的疾病调节疗法(DMT)的注册前和上市后的数据，包括β干扰素、格列聚醋酸酯、Fingolimod、Teriflunomide、富马酸二甲酯、Cladriine、Natalizumab、alemtuzumab和ocriszumab。我们回顾了文献中提出的因果机制，并讨论了病毒性肝炎或肝硬变患者使用DMT等问题。大多数数据是在上市后阶段通过向国家药物警戒机构报告和发布病例报告或病例系列而出现的。严重的肝脏不良事件很少见，但确切的发生率以及预测因素在很大程度上是未知的。不幸的是，目前可用于治疗多发性硬化症的DMT中没有一种没有潜在的肝脏毒性作用。据报道，β-干扰素、Fingolimod、Natalizumab、alemtuzumab和ocriszumab通过不同的机制(特异性反应、自身免疫性肝炎或病毒再激活)导致急性肝功能衰竭。多发性硬化症患者应该被告知他们的治疗可能产生的肝脏副作用。大多数肝损伤病例都是特殊的和不可预测的。已经审查了每个DMT的具体监测计划，临床医生应该准备好识别提示肝损伤的临床症状。并非所有的DMT都适用于肝硬变患者。对于一些DMT，在开始治疗之前需要对乙肝病毒和丙型肝炎病毒进行筛查，并且已经建立了监测或抗病毒预防时间表。由于疾病恶化的风险，乙型干扰素、醋酸格拉替拉默、那他珠单抗和阿仑珠单抗在自身免疫性肝炎中相对禁忌。许多疾病修正疗法(DMT)被批准用于多发性硬化症的治疗，但肝脏损伤是一个令人担忧的问题。在DMT治疗期间，患者可能会出现转氨酶升高，在极少数情况下，会出现特殊的和不可预测的急性肝功能衰竭。目前，还不可能预测或预防严重的肝脏相关不良事件。此外，在DMT治疗期间，也可能发生自身免疫性肝炎和病毒重新激活。由于不良事件被严重低估，重要的是在文献中报告与肝脏相关的严重不良事件的病例，并提供足够的因果关系文件，以更好地了解DMT的肝脏安全性概况。
In this narrative review, we analyze pre-registration and post-marketing data concerning hepatotoxicity of all disease-modifying therapies (DMTs) available for the treatment of relapsing-remitting multiple sclerosis, including beta interferon, glatiramer acetate, fingolimod, teriflunomide, dimethyl fumarate, cladribine, natalizumab, alemtuzumab, and ocrelizumab. We review the proposed causal mechanisms described in the literature and we also address issues like use of DMTs in patients with viral hepatitis or liver cirrhosis. Most data emerged in the post-marketing phase by reports to national pharmacovigilance agencies and published case reports or case series. Serious liver adverse events are rare, but exact incidence is largely unknown, as are predictive factors. Unfortunately, none of the DMTs currently available for the treatment of multiple sclerosis is free of potential hepatic toxic effects. Cases of acute liver failure have been reported for beta-interferon, fingolimod, natalizumab, alemtuzumab, and ocrelizumab by different mechanisms (idiosyncratic reaction, autoimmune hepatitis, or viral reactivation). Patients with multiple sclerosis should be informed about possible hepatic side effects of their treatment. Most cases of liver injury are idiosyncratic and unpredictable. The specific monitoring schedule for each DMT has been reviewed and the clinician should be ready to recognize clinical symptoms suggestive for liver injury. Not all DMTs are indicated in cirrhotic patients. For some DMTs, screening for hepatitis B virus and hepatitis C virus is required before starting treatment and a monitoring or antiviral prophylaxis schedule has been established. Beta interferon, glatiramer acetate, natalizumab, and alemtuzumab are relatively contraindicated in autoimmune hepatitis due to the risk of disease exacerbation. Many disease-modifying therapies (DMTs) are approved for multiple sclerosis treatment, but liver injury is a concern. Patients can experience transaminase elevation during DMT treatment, and in rare cases, idiosyncratic and unpredictable acute liver failure. Currently, it is not possible to predict or prevent serious liver-related adverse events. Furthermore, autoimmune hepatitis and viral reactivation can also occur during DMT treatments. Since adverse events are greatly underreported, it is important to report cases of serious liver-related adverse events in the literature with adequate causality documentation to better understand the liver safety profiles of DMTs.
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