Liver Function After Intravenous Methylprednisolone Administration

Summary

Graves' orbitopathy (GO) is a characterized by orbital soft tissue inflammation and oedema associated with glycosaminoglycan deposition and fibrosis. The most frequent cause is Graves' disease. The classification is comprised based on the severity of orbital changes ranging from mild, moderate-to-severe GO and sight-threatening GO, which includes dysthyroid optic neuropathy (DON). Intravenous methylprednisolone (IVMP) pulse therapy is the first-line treatment in the active-phase of moderate-to-severe GO and DON. This therapy is more effective and better tolerated than oral glucocorticoids (GCs). The current recommendation of the European Group of Graves' Orbitopathy (EUGOGO) is that cumulative doses of IVMP should not exceed 8.0g in each treatment course, and pulses should not be given on consecutive or alternate days, except in the case of DON. According to EUGOGO recommendations patients with moderate-to-severe GO are treated with IVMP cumulative dose 4.5g during a 12-week period (for the first 6 weeks 0.5g IVMP per week, for the next 6 weeks 0.25g IVMP per week). According to EUGOGO recommendations patients with DON should receive 3.0g IVMP (1.0g/day for 3 consecutive days) as the basic treatment. This limitation in doses are due to the necessity of the prevention of severe side effects that are rare but may be fatal. One of the most severe adverse events is acute liver injury (ALI), in some cases irreversible and/or fatal. The estimated morbidity and mortality of ALI was found to be 1-4 % and 0.01-0.3%, respectively. Since 2000, there were 5 reported fatal cases.

Mechanisms causing an IVMP-induced ALI remains incompletely elucidated. There are some possible hypotheses that may explain the occurrence of ALI. Firstly, GCs can lead to reactivation of autoimmune hepatitis: an immune "rebound phenomenon" following GCs withdrawal. The second mechanism of ALI is reactivation of viral hepatitis. Finally, there is well known direct toxic effect of GCs on hepatocytes, probably dose-dependent.

This study was performed to evaluate the influence of two different, routinely used schemes of therapy with IVMP in patients with moderate-to-severe GO (first scheme) and DON (second scheme) on biochemical liver parameters. Patients included into the study were treated according to EUGOGO recommendations with routine doses of IVMP and routine scheme of administration for moderate-to-severe GO and DON. No additional treatment was performed during the study protocol.

Conditions

• Graves Disease
• Graves Ophthalmopathy
• Liver Diseases
• Liver Failure
• Liver Injury
• Liver Dysfunction
• Liver Insufficiency
• Acute Liver Failure
• Acute Liver Injury
• Acute Liver Injury, Drug Induced
• Methylprednisolone Adverse Reaction
• Glucocorticoids Toxicity
• Dysthyroid Orbitopathy
• Dysthyroid Ophthalmopathy

Interventions

DRUG

every week IVMP therapy

12 pulses of intravenous methylprednisolone (IVMP) in every week schedule (for the first 6 weeks 0.5g IVMP per week, for the next 6 weeks 0.25g IVMP per week; cumulative dose 4.5g) according to EUGOGO recommendations

DRUG

very high doses IVMP therapy

3 pulses of intravenous methylprednisolone (IVMP) (1.0g/day for 3 consecutive days; cumulative dose 3.0g) according to EUGOGO recommendations

Sponsors & Collaborators

• Medical University of Warsaw

  lead OTHER

Principal Investigators

• Piotr Miśkiewicz, MD, PhD · Medical University of Warsaw

Study Design

Allocation

NON_RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-01-01

Primary Completion

2016-10-30

Completion

2016-10-30