Liver injury after methylprednisolone pulses

A disputable cause of hepatotoxicity. A case series and literature review

Zoubek, Miguel Eugenio
Pinazo-Bandera, José
Ortega-Alonso, Aida
Hernández, Nelia
Crespo, Javier
Contreras, Fernando
Medina-Cáliz, Inmaculada
Sanabria-Cabrera, Judith
Sanjuan-Jiménez, Rocío
González-Jiménez, Andrés
García-Cortés, Miren
Lucena, M Isabel
Andrade, Raúl J
Robles-Díaz, Mercedes

¹UGC Digestivo y Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), H U Virgen de la Victoria, Malaga, Spain
²Department of Toxicology, School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
³Hospital de Clínicas, Clínica Gastroenterología, F Medicina, Montevideo, Uruguay
⁴Unidad de Gestión Clínica de Enfermedades Digestivas, Hospital Marqués de Valdecilla, Instituto de Investigación Biomédica Marques de Valdecilla (IDIVAL), Santander, Spain
⁵Departamento de Gastroenterología, National University Pedro Henríquez Ureña, Santo Domingo, Dominican Republic
⁶Unidad Investigación Clínica y Ensayos ClÚcos (UICEC)-Instituto de Investigacióe Biomedicina de Málaga (IBIMA), Plataforma Spanish Clinical Research Network (SCReN), Málaga Spain
⁷Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Madrid, Spain

*Co-senior authorship

Mercedes Robles-Díaz, UGC Digestivo, H U Virgen de la Victoria, Málaga 29010, Spain. Email: [email protected]

Received December 31, 2018

Accepted February 17, 2019

United European Gastroenterology Journal 7(6):p 825-837, July 2019. | DOI: 10.1177/2050640619840147

Background and Objectives

Corticosteroids are often empirically used to treat idiosyncratic hepatotoxicity with severe features. Interestingly, intravenous methylprednisolone (MP) is increasingly being recognized as being responsible for liver injury. We aimed to characterize MP-induced liver injury by analyzing demographical, clinical, laboratory and outcome data of three MP-induced hepatotoxicity cases and compared this information with that of previously published cases.

Case series

Three females with multiple sclerosis (MS) were treated intravenously with MP, mean daily dose 767 mg. Liver damage occurred 2 to 6 weeks after exposure. Severity was mild to moderate. Two patients suffered positive rechallenge.

Literature review

We identified 50 published cases of MP hepatotoxicity. Most of these cases were female (86%) and main treatment indications were MS (29 cases) and Graves' ophthalmopathy (13 cases). Hepatocellular damage predominated and mean time to onset was 6 weeks. Four patients died and rechallenge occurred in 19 cases.

Conclusion

MP pulses can induce severe liver injury, often with an autoimmune phenotype, particularly in patients with MS and Graves' ophthalmopathy. Consequently, these patient groups should have liver tests monitored when treated with MP to provide safer patient care.