title: Acute liver damage following intravenous glucocorticoid treatment for Graves' ophthalmopathy.
abstract: OBJECTIVE
  Over the last years, there have been several reports on the occurrence of acute liver damage (ALD) in patients affected with Graves' ophthalmopathy (GO) receiving intravenous glucocorticoids (ivGCs). This article is aimed at reviewing the literature on this specific topic and reporting two new cases of ALD occurring in GO patients while on ivGCs.
  
  
  METHODS
  The terms "glucocorticoid therapy" and "Graves' Ophthalmopathy"/"Graves' Orbitopathy"/"Thyroid eye disease" were used both separately and in conjunction with the terms "liver disease," "liver damage," "hepatotoxicity," "liver failure," to search MEDLINE for articles published since the first report of ALD in 2000 and up to 2015.
  
  
  RESULTS
  ALD [defined as an increase in alanine aminotransferase (ALT) >300 U/L] during or after completion of ivGCs has been so far reported in 17 fully documented cases. Overall, one-half of those patients were diagnosed as having autoimmune hepatitis (AIH) and in the vast majority of the remaining cases a diagnosis of methylprednisolone(MP)-induced hepatotoxicity was suspected. The clinical course of liver injury varied from asymptomatic hypertransaminasemia in the vast majority of patients to fatal hepatic failure in four patients receiving higher (>8 g) cumulative doses of MP.
  
  
  CONCLUSIONS
  The overall risk of ALD is relatively low (~1 %), and seems higher using a single dose >0.5 g and a cumulative dose >8.5 g MP. Whenever ivGC treatment is required, serum liver enzymes, viral hepatitis markers, and autoantibodies related to AIH should be obtained prior to ivGC administration. Liver function should be monitored during ivGC and up to 6 months after the end of treatment. Prolonging observation after 6 months is likely unnecessary, since all cases of ALD so far reported always occurred well within this term.
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, University of Messina, Messina, Italy. mmoleti@unime.it.
authors.forename: Mariacarla
authors.identifier: http://orcid.org/0000-0002-8686-1615
authors.initials: M
authors.lastname: Moleti
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, University of Messina, Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giuffrida
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, University of Messina, Messina, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Sturniolo
authors.affiliation: Dipartimento di Patologia Umana dell'adulto e dell'età evolutiva, University of Messina, Messina, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Squadrito
authors.affiliation: Dipartimento di Scienze Radiologiche, Sezione di Medicina Nucleare University of Messina, Messina, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Campennì
authors.affiliation: Dipartimento di Medicina, University of Perugia, Perugia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Morelli
authors.affiliation: Dipartimento di Medicina, University of Perugia, Perugia, Italy.
authors.forename: Efisio
authors.initials: E
authors.lastname: Puxeddu
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, University of Pisa, Pisa, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Sisti
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, University of Messina, Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Trimarchi
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, University of Messina, Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Vermiglio
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, University of Pisa, Pisa, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Marinò
mesh_terms: D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D049970:Graves Ophthalmopathy / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged
chemical_list: D005938:Glucocorticoids; D008775:Methylprednisolone
keywords: Acute liver damage; Graves’ ophthalmopathy; Hepatotoxicity; Intravenous glucocorticoid therapy; Methylprednisolone