Does Prednisone Increase Transaminases?
No, prednisone does not directly increase transaminases; in fact, it is used therapeutically to normalize elevated transaminases in autoimmune hepatitis, where 80% of patients achieve ALT less than twice the upper limit of normal within 6 months of treatment. 1
Prednisone's Effect on Liver Enzymes in Autoimmune Hepatitis
Prednisone actively reduces transaminases in autoimmune hepatitis rather than elevating them. The evidence from multiple high-quality guidelines demonstrates:
In autoimmune hepatitis treatment, prednisolone (the active metabolite of prednisone) at doses of 0.5-1 mg/kg/day leads to normalization of transaminases and IgG levels as the primary therapeutic goal. 1
80% of patients treated with prednisolone alone or prednisolone plus azathioprine achieve serum ALT less than twice the upper limit of normal within 6 months. 1
In non-responding patients with autoimmune hepatitis, increasing prednisone to approximately 60 mg/day is recommended to improve biochemical parameters, including transaminases. 1
FDA-Labeled Adverse Effects
The FDA drug label for prednisone lists "elevation in serum liver enzyme levels (usually reversible upon discontinuation)" under gastrointestinal adverse reactions. 2 However, this is listed as a rare adverse effect and must be contextualized:
This elevation is described as "usually reversible upon discontinuation," suggesting it is an uncommon idiosyncratic reaction rather than a predictable pharmacologic effect. 2
The incidence is not quantified in the FDA label, indicating it is not a common or dose-dependent phenomenon. 2
Pharmacology-Related Considerations
Transaminase elevations from corticosteroids, when they occur, may represent "pharmacology-related elevation" through modification of gluconeogenesis rather than true hepatotoxicity. 3
Drugs that modify gluconeogenesis or glucose metabolism can slightly increase transaminase activities without evidence of drug-induced liver injury (DILI). 3
In patients with active liver disease, prednisone metabolism is altered: there is impaired conversion of prednisone to prednisolone (the active form), but also impaired degradation of prednisolone, resulting in different levels of biologically active corticosteroids. 4
Clinical Context: Severe Drug-Induced Liver Injury
In severe drug-induced liver injury (DILI), prednisone does not worsen transaminase elevations but also does not provide benefit. 5
A 2019 observational study found that serum bilirubin and transaminase values gradually decreased in both prednisone-treated and control groups, with no significant differences between groups. 5
High-dose prednisone (>40 mg daily) was actually detrimental in severe DILI, with lower cumulative rates of severity reduction compared to low-dose or no prednisone. 5
Critical Clinical Pearls
When evaluating transaminase elevations in patients on prednisone, consider these key points:
If transaminases are elevated in a patient on prednisone for autoimmune hepatitis, this represents inadequate disease control or non-response, not a drug effect. 1
Baseline liver function tests prior to initiating corticosteroid therapy are recommended in patients with known liver dysfunction, with follow-up studies one month later. 6
In patients with active liver disease and low serum albumin, higher levels of unbound prednisolone circulate, resulting in different biological activity compared to patients without liver disease. 4
Transaminase elevations are not specific to hepatic injury and can occur from extrahepatic causes, nutritional factors, or hormonal modifications of gluconeogenesis. 3, 7