Can steroids cause an increase in liver enzyme levels, specifically alanine transaminase (ALT) and aspartate transaminase (AST)?

From the Guidelines

Steroids can indeed cause an increase in liver enzyme levels, specifically alanine transaminase (ALT) and aspartate transaminase (AST), as evidenced by the management guidelines for immune-mediated liver injury caused by immune checkpoint inhibitors 1.

Key Points to Consider

• The elevation in liver enzymes occurs because steroids can directly damage liver cells, leading to the release of these enzymes into the bloodstream.
• Patients taking steroids should have regular liver function tests, especially during the first few months of treatment.
• If ALT or AST levels rise to more than three times the upper limit of normal, dose reduction or discontinuation may be necessary, as outlined in the guidelines for managing treatment-emergent abnormal hepatic biochemical tests in clinical trials with ICIs 1.
• The liver enzyme elevations are usually reversible once the steroids are stopped, with levels typically returning to normal within weeks to months after discontinuation.

Management of Liver Enzyme Elevation

• For grade 1 ALT elevation (ALT > ULN-3x ULN), closer monitoring is recommended, with no treatment interruption necessary 1.
• For grade 2 serum ALT elevation (ALT > 3-5x ULN), withholding ICI treatment and initiating close monitoring is recommended, with oral corticosteroid therapy (prednisolone, methylprednisolone or equivalent) at a dose of 0.5–1 mg/kg/day if ALT returns to baseline values within 1–2 weeks 1.
• For grade 3 or 4 serum ALT elevation (> 5x ULN), withholding of ICI therapy and initiating corticosteroid therapy (prednisolone, methylprednisolone or equivalent) at 1–2 mg/kg/day is recommended, with consideration of permanent discontinuation of ICI therapy if no improvement occurs after initiation of corticosteroids 1.

From the FDA Drug Label

Reversible changes in liver function tests also occur including increased bromsulfophthalein (BSP) retention, changes in alkaline phosphatase and increases in serum bilirubin, aspartate aminotransferase (AST, SGOT) and alanine aminotransferase (ALT, SGPT)

Yes, steroids can cause an increase in liver enzyme levels, specifically:

• Alanine transaminase (ALT)
• Aspartate transaminase (AST) 2

From the Research

Liver Enzyme Increase Due to Steroids

• Steroids can cause an increase in liver enzyme levels, specifically alanine transaminase (ALT) and aspartate transaminase (AST) 3, 4, 5.
• A study found that a 26-year-old male bodybuilder who self-administered high doses of androgenic/anabolic steroids had significantly elevated AST and ALT levels, with AST at 5,870 IU/L and ALT at 10,580 IU/L 3.
• Another study discovered that 29% and 33% of patients treated with stanozolol or placebo, respectively, had significantly elevated AST and ALT levels, which returned to baseline after treatment cessation 4.
• The use of anabolic steroids can lead to hepatotoxicity, characterized by elevated liver transaminases, acute cholestatic syndrome, chronic vascular injury, hepatic tumors, and toxicant-associated fatty liver disease 5.

Factors Influencing Liver Enzyme Increase

• The frequency and severity of side effects, including liver enzyme increase, depend on factors such as the formulation of the drug, route of administration, dosage, duration of use, and individual sensitivity and response 5.
• Supraphysiologic doses or multiple steroids and other drugs taken simultaneously can increase the risk of adverse effects, including liver enzyme increase 5.

Assessment of Liver Function

• When evaluating hepatic function in cases of anabolic steroid therapy or abuse, creatine kinase (CK) and gamma-glutamyltranspeptidase (GGT) levels should be considered in addition to ALT and AST levels 6.
• Prior reports of anabolic steroid-induced hepatotoxicity based on elevated aminotransferase levels may have been overstated, as exercising subjects, including steroid users, may have elevated CK and normal GGT levels 6.