Betamethasone and Liver Function Test Elevations
Betamethasone can cause elevations in liver function tests, though this is uncommon, and the FDA label lists "elevation in serum liver enzyme levels (usually reversible upon discontinuation)" as a known adverse reaction. 1
Direct Evidence of Corticosteroid-Induced Hepatotoxicity
While corticosteroid-induced liver injury is rare, it is well-documented:
Case reports demonstrate that betamethasone specifically can cause severe hepatotoxicity, including one documented case of acute liver failure requiring plasma exchange after betamethasone administration for sudden-onset deafness, with AST reaching 18,000 U/L and ALT 12,000 U/L. 2
Methylprednisolone (a related corticosteroid) has caused acute hepatitis with RUCAM scores of 6-10 (probable to highly probable causality), with multiple cases showing positive rechallenge confirming the diagnosis. 3
The hepatotoxic effect appears dose-dependent and can occur with high-dose pulse therapy, as seen in multiple sclerosis patients receiving methylprednisolone. 3
Mechanisms and Risk Factors in Liver Disease
In patients with pre-existing liver disease, corticosteroids pose additional concerns beyond direct hepatotoxicity:
Corticosteroids may lead to increased fat deposition in the liver, which is particularly concerning in patients with pre-existing steatosis and should be considered in decision-making. 4
Patients with chronic liver disease have impaired cortisol metabolism, resulting in elevated non-protein bound corticosteroid levels and increased sensitivity to corticosteroid therapy, suggesting reduced dosing may be advisable. 5
Corticosteroid metabolism is altered differently depending on the specific agent and type of organ dysfunction: dexamethasone shows prolonged half-life in liver disease but accelerated metabolism in renal failure, while prednisolone shows reduced clearance in renal failure but not liver disease. 6
Critical Risk: HBV Reactivation
The most clinically significant liver-related risk with corticosteroids is hepatitis B virus reactivation, which can cause hepatitis flare and acute liver failure:
Screening for HBsAg is mandatory before corticosteroid therapy, and antiviral prophylaxis with nucleoside analogues is recommended in all HBsAg-positive patients receiving corticosteroids. 4
Particular attention should be paid to HBcAb-positive candidates in whom occult HBV infection could be reactivated after immunosuppression. 4
Monitoring Recommendations
When administering corticosteroids to patients with liver concerns:
Perform baseline liver function tests before initiating therapy if liver disease is suspected. 7
Monitor LFTs at 2-4 weeks after starting therapy, with increased frequency if any elevation occurs. 7, 8
For patients on potentially hepatotoxic medications, monitor LFTs twice weekly. 4, 8
If moderate-to-severe liver injury develops (ALT >5× ULN or ALP >2× ULN with total bilirubin >2× ULN), discontinue the corticosteroid immediately. 4
Clinical Context: Beneficial Effects on LFTs
Paradoxically, corticosteroids are used therapeutically to manage ALT elevations in specific contexts:
In gene therapy patients, corticosteroids (prednisone 60 mg/day) are the standard treatment for ALT elevations, with the goal of preserving therapeutic response. 4
In HELLP syndrome, betamethasone administration significantly improves liver function, with ALT decreasing by 31.6 IU/L and AST by 52.1 IU/L, with two doses of 12 mg betamethasone given 12 hours apart being most effective. 9
Key Pitfalls to Avoid
Do not attribute all LFT abnormalities to corticosteroids alone—investigate for underlying disease processes, viral hepatitis, or other hepatotoxic medications. 7, 10
Do not delay investigation of persistent LFT abnormalities—if tests fail to normalize within 8-12 weeks after discontinuation, investigate for chronic liver diseases. 7, 8
Do not ignore signs of hepatic decompensation—urgent referral is needed for progressive deterioration, acute liver failure signs, or severe elevation with bilirubin >2× ULN. 7, 10
Do not overlook the possibility of autoimmune hepatitis mimicking corticosteroid-induced injury, particularly in patients with underlying autoimmune conditions—unintended rechallenge can help distinguish between the two. 3