Department of Neurology, Osaka City University Graduate School of Medicine, Japan.
Department of Neurology, Osaka City University Graduate School of Medicine, Japan.
Mult Scler Relat Disord. 2020 Jul;42:102065. doi: 10.1016/j.msard.2020.102065. Epub 2020 Mar 23.
In patients with multiple sclerosis (MS), development of hepatic injury has been sporadically reported after methylprednisolone (MP) pulse therapy. Some studies suggest autoimmune hepatitis, while other studies reported direct hepatotoxicity as a cause for hepatic injury. Here, we studied the pathological mechanism of such liver injury in patients with MS.
From 2005 to 2016, eight patients with MS developed liver injury after MP pulse therapy. Their average age was 38 years (range: 28-49 years, all female). Autoimmune antibodies were measured and a liver biopsy was performed in seven patients.
Liver injury developed within two weeks in two patients and later (30-90 days after MP) in six patients. No hepatitis-related autoantibody or hepatitis virus were found. All cases were classified as hepatocellular injury and none as cholestatic or mixed. A liver biopsy in five cases revealed centrilobular necrosis with lobular infiltrates of inflammatory cells, suggesting drug-induced acute hepatitis. The biopsy findings in another case suggested a residual stage of acute hepatitis. Only one patient showed portal expansion with periportal fibrosis, suggesting autoimmune hepatitis. All patients recovered spontaneously or with only hepatoprotective drugs, although one patient with possible autoimmune hepatitis recovered slowly.
Liver injury develops usually later than two weeks after MP treatment. The prognosis is good in most cases and rarely autoimmune hepatitis may be involved.
在多发性硬化症(MS)患者中,甲基强的松龙(MP)脉冲治疗后偶尔会出现肝损伤。一些研究提示自身免疫性肝炎,而其他研究则报道直接肝毒性是肝损伤的原因。在此,我们研究了 MS 患者此类肝损伤的病理机制。
2005 年至 2016 年,8 例 MS 患者在 MP 脉冲治疗后发生肝损伤。他们的平均年龄为 38 岁(范围:28-49 岁,均为女性)。在 7 例患者中测量了自身抗体并进行了肝活检。
2 例患者在两周内发生肝损伤,6 例患者在 MP 后较晚(30-90 天)发生。未发现肝炎相关自身抗体或肝炎病毒。所有病例均归类为肝细胞损伤,无胆汁淤积或混合性。5 例肝活检显示中央小叶坏死伴小叶炎性细胞浸润,提示药物诱导的急性肝炎。另一个病例的活检结果提示急性肝炎的残留阶段。只有 1 例患者表现为门脉扩张伴门周纤维化,提示自身免疫性肝炎。尽管 1 例可能患有自身免疫性肝炎的患者恢复缓慢,但大多数患者均自发或仅用肝保护药物恢复。
肝损伤通常在 MP 治疗后两周后才发生。大多数情况下预后良好,很少涉及自身免疫性肝炎。