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.

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缓解疗法（DMT）的肝毒性的注册前和上市后数据，包括β干扰素、醋酸格拉替雷、芬戈莫德、特立氟胺、富马酸二甲酯、克拉屈滨、那他珠单抗、阿仑单抗和奥瑞珠单抗。我们回顾了文献中描述的拟议因果机制，并解决了病毒性肝炎或肝硬化患者使用 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以及发布的病例报告或病例系列得出的。严重的肝脏不良事件很少见，但确切的发生率和预测因素在很大程度上尚不清楚。不幸的是，目前可用于治疗多发性硬化症的 DMT 均不具有潜在的肝毒性作用。据报道，β-干扰素、芬戈莫德、那他珠单抗、阿仑单抗和奥瑞珠单抗通过不同机制（特异质反应、自身免疫性肝炎或病毒再激活）导致急性肝衰竭病例。应告知多发性硬化症患者其治疗可能产生的肝脏副作用。大多数肝损伤病例都是特殊且不可预测的。每个 DMT 的具体监测计划均已审查，临床医生应准备好识别提示肝损伤的临床症状。并非所有 DMT 都适用于肝硬化患者。对于某些DMT，在开始治疗之前需要筛查乙型肝炎病毒和丙型肝炎病毒，并已制定监测或抗病毒预防计划。 由于存在疾病恶化的风险，β干扰素、醋酸格拉替雷、那他珠单抗和阿仑单抗在自身免疫性肝炎中相对禁忌。