Methylprednisolone and hepatotoxicity in Graves' ophthalmopathy

Immunosuppressive therapy with glucocorticoids alone or in combination with radiotherapy is first-choice treatment for the active phase of Graves' ophthalmopathy (GO). Intravenous methylprednisolone (mPRED) pulse therapy is much more effective, safer, and better tolerated than steroids orally administered. There have been some reports, however, of unfavorable reactions to mPRED pulse therapy on liver function. Here, we report laboratory test results in patients with GO before and after intravenous mPRED therapy.

Thirty patients (24 women and 6 men) whose mean age was ± standard error of the mean 53±1.3 participated in the study. All patients were treated with mPRED for their history of GO. None had received radiotherapy before mPRED. There was no history of liver disease including viral hepatitis in any of the patients. A battery of tests including general serum chemistries and liver function tests as well as those relating to clotting parameters and viral forms of hepatitis were performed a week before and 2 days after mPRED therapy.

mPRED pulse therapy caused a significant, below reference range, decrease in alkaline phosphatase activity from 119.43±14.98 to 105.53±13.98 IU/L and an increase in gamma-glutamyltranspeptidase activity (above reference range, but not statistically significant) from 23.76±2.93 to 25.3±1.52 IU/L. No significant changes were noted in other liver enzymes activities. We also observed a significant, below reference range, decrease in serum total protein as well as a significant, above reference range, increase of alpha-1 globulins, and low-density lipoproteins cholesterol levels. Pulse therapy also resulted in a significant, but still within reference range, decreases in activated partial thromboplastin time (APTT) from 29.03±0.86 to 26.13±1.16 s, fibrinogen from 3.85±0.2 to 3.05±0.13 g/L, and increase of International Normalized Ratio (INR) from 1.06±1.06 to 1.11±0.06. Despite a lack of a history of viral hepatitis, six patients had positive tests for anti-Hepatitis B e (HBe) antibodies before mPRED administration. In two of these patients, anti-HBe antibody tests became negative after mPRED treatment. In two of the six patients who had positive anti-HBe antibodies, anti-HBc antibodies in the IgG class were also present before and after mPRED treatment. Another patient was found to have anti-HBc IgG both before and after mPRED treatment. Other markers of A and C viral hepatitis were negative in all patients.

Patients who are on anticoagulents need careful monitoring of their INR, APTT, and fibrinogen while on mPRED therapy. We recommend at least once a week. In patients without evidence for active viral replicating disease, but with past hepatitis B, as judged by the presence of pertinent markers, mPRED pulse therapy for GO does not appear to reactivate hepatitis B.