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多发性硬化症患者静脉注射甲基泼尼松龙冲击治疗后的肝损伤:来自单一学术性肝病中心的经验

Liver Injury Following Intravenous Methylprednisolone Pulse Therapy in Multiple Sclerosis: The Experience from a Single Academic Liver Center.

作者信息

Kounatidis Dimitris, Vallianou Natalia G, Kontos Georgios, Kranidioti Hariklia, Papadopoulos Nikolaos, Panagiotopoulos Alexandros, Dimitriou Krystalia, Papadimitropoulos Vasileios, Deutsch Melanie, Manolakopoulos Spilios, Vassilopoulos Dimitrios, Koskinas John

机构信息

Second Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, 11527 Athens, Greece.

Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece.

出版信息

Biomolecules. 2025 Mar 19;15(3):437. doi: 10.3390/biom15030437.

Abstract

Intravenous methylprednisolone (IVMP) pulses, widely used for managing multiple sclerosis (MS) exacerbations, can lead to acute liver injury, presenting a diagnostic challenge in distinguishing between drug-induced autoimmune-like hepatitis (DI-ALH) and idiopathic autoimmune hepatitis (AIH). This study aimed to delineate the clinical and biochemical features of IVMP-induced liver injury, discern its etiology, and evaluate the efficacy of glucocorticoid (GC) therapy in treatment. A retrospective analysis of 13 relapsing MS patients with IVMP-induced liver injury was conducted. Liver injury was classified as hepatocellular, cholestatic, or mixed, with severity assessment guiding liver biopsy in selected cases. Causality was assessed using the Roussel Uclaf Causality Assessment Method (RUCAM) and the Simplified Diagnostic Criteria for AIH. All patients were initially monitored for a minimum of six months, with a mean follow-up period of 4.30 years. The median onset of liver injury was 37.46 days post-IVMP, with a mean peak alanine transaminase (ALT) level of 618.46 U/L. antinuclear antibody (ANA) positivity was observed in 61.53% of cases, with elevated serum immunoglobulin G (IgG) at 15.38%. Hepatocellular injury was universal among patients, and causality assessment predominantly supported DI-ALH. GC therapy was administered in six cases, achieving favorable outcomes in all but one, which necessitated rituximab. Biochemical normalization occurred within a mean of 55.41 days, with GC-treated patients recovering faster (48 days). These findings support the hypothesis that IVMP can induce hepatocellular injury, likely DI-ALH, during MS exacerbations. A tapering GC regimen proved effective in promoting recovery, particularly in severe cases. Additionally, this study introduced a diagnostic and therapeutic algorithm for managing IVMP-induced liver injury, offering a practical framework for clinical application.

摘要

静脉注射甲泼尼龙(IVMP)冲击疗法广泛用于治疗多发性硬化症(MS)急性发作,但可导致急性肝损伤,这给鉴别药物性自身免疫样肝炎(DI-ALH)和特发性自身免疫性肝炎(AIH)带来了诊断挑战。本研究旨在描述IVMP所致肝损伤的临床和生化特征,明确其病因,并评估糖皮质激素(GC)治疗的疗效。对13例复发型MS患者IVMP所致肝损伤进行回顾性分析。肝损伤分为肝细胞型、胆汁淤积型或混合型,在部分病例中根据严重程度评估指导肝活检。采用鲁塞尔·优克福因果关系评估法(RUCAM)和AIH简化诊断标准评估因果关系。所有患者最初至少监测6个月,平均随访期为4.30年。肝损伤的中位发病时间为IVMP治疗后37.46天,平均谷丙转氨酶(ALT)峰值水平为618.46 U/L。61.53%的病例抗核抗体(ANA)呈阳性,15.38%的病例血清免疫球蛋白G(IgG)升高。肝细胞损伤在患者中普遍存在,因果关系评估主要支持DI-ALH。6例患者接受了GC治疗,除1例需要使用利妥昔单抗外,其余均取得了良好效果。生化指标平均在55.41天内恢复正常,接受GC治疗的患者恢复更快(48天)。这些发现支持了以下假设:在MS急性发作期间,IVMP可导致肝细胞损伤,可能为DI-ALH。逐渐减量的GC方案被证明对促进恢复有效,尤其是在严重病例中。此外,本研究还介绍了一种管理IVMP所致肝损伤的诊断和治疗算法,为临床应用提供了一个实用框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19b9/11940579/543cad526a37/biomolecules-15-00437-g001.jpg

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