Management of Abnormal LFTs and Elevated Ferritin in a Patient on Wegovy, Allopurinol, and Metoprolol
Immediately discontinue Wegovy and iron supplementation (Ferograd), obtain urgent abdominal ultrasound and viral hepatitis/autoimmune workup, and repeat LFTs in 2-4 weeks to assess for drug-induced liver injury, as the progressive worsening mixed hepatocellular-cholestatic pattern (ALT rising from 30 to 154, GGT from 67 to 102) strongly suggests medication-related hepatotoxicity.
Immediate Actions for Abnormal LFTs
Discontinue Potentially Hepatotoxic Medications
Stop Wegovy (semaglutide) immediately as GLP-1 receptor agonists can cause hepatocellular injury, particularly given the temporal relationship where LFTs began deteriorating and then accelerated after Wegovy initiation 1.
Discontinue iron supplementation (Ferograd) as the patient has elevated ferritin (380 ng/mL) without anemia (Hb 141 g/L), and continued iron supplementation risks further hepatic iron accumulation 1.
Review all other medications for hepatotoxicity potential, though allopurinol and metoprolol at these doses are less likely culprits given the timing 1.
Urgent Diagnostic Workup
Obtain abdominal ultrasound to evaluate for structural liver disease, biliary obstruction, or hepatic steatosis given the mixed hepatocellular-cholestatic pattern 1.
Complete viral hepatitis screening (HBsAg, anti-HBc, anti-HCV) and autoimmune markers (ANA, ASMA, ANCA if suspicion for autoimmune hepatitis is high) to exclude alternative etiologies 1.
Check GGT levels to confirm the cholestatic component, as isolated alkaline phosphatase elevation (139) requires GGT confirmation to distinguish hepatic from bone sources 1.
Consider liver biopsy only if LFTs fail to improve after medication discontinuation or if alternative diagnoses would alter management 1.
Management of Elevated Ferritin
Interpretation in This Clinical Context
The ferritin of 380 ng/mL is likely multifactorial: secondary to ongoing knee inflammation (acute phase reactant) and potentially contributing to hepatic injury 2, 3.
Ferritin is an independent predictor of hepatic steatosis in patients with abnormal LFTs, and the correlation between elevated ferritin and liver enzyme abnormalities suggests this may be contributing to the hepatocellular injury pattern 2.
This is NOT iron overload requiring phlebotomy: the patient has normal hemoglobin (141 g/L), no evidence of hemochromatosis, and ferritin remains well below levels associated with organ damage (typically >1000 ng/mL) 1.
Monitoring Strategy
Recheck ferritin in 4-6 weeks after discontinuing iron supplementation and once knee inflammation resolves to establish a true baseline 1.
Monitor ferritin levels should not exceed 500 ng/mL to avoid potential toxicity, particularly given the concurrent liver dysfunction 1.
If ferritin remains elevated (>500 ng/mL) after inflammation resolves and iron supplementation is stopped, consider iron studies including transferrin saturation and genetic testing for hereditary hemochromatosis (HFE mutations) 1.
LFT Monitoring and Grading
Current Grade Assessment
- This represents Grade 3 hepatotoxicity (ALT >5× ULN if baseline was 30, now 154; though absolute values suggest Grade 2-3 range) with mixed hepatocellular-cholestatic pattern 1.
Follow-up Protocol
Repeat LFTs in 2-4 weeks after medication discontinuation to assess for improvement 1.
If LFTs improve to Grade 1 or less (ALT <3× ULN), continue monitoring every 4-6 weeks until normalization 1.
If LFTs worsen or fail to improve after 3-5 days of medication discontinuation, consider initiating corticosteroids (0.5-1 mg/kg/day prednisone equivalent) for drug-induced liver injury, though this should be done in consultation with hepatology 1.
Do NOT restart Wegovy if LFTs were medication-related; permanent discontinuation is recommended for Grade 3 hepatotoxicity 1.
Addressing the Underlying Conditions
Weight Management Without Wegovy
Given the need to discontinue Wegovy, focus on non-pharmacologic weight management strategies including dietary modification and the patient's current cycling regimen for muscle strengthening.
Once LFTs normalize, consider alternative weight loss medications with lower hepatotoxicity risk if medically necessary, but only after complete resolution of liver enzyme abnormalities.
Gout and Allopurinol Management
Continue allopurinol 300 mg daily as the uric acid is well-controlled (0.24, target <0.36) and allopurinol is less likely the culprit given stable dosing [@patient history@].
Allopurinol-induced hepatotoxicity typically presents earlier in treatment course, not after prolonged stable use.
Common Pitfalls to Avoid
Do not continue iron supplementation in a patient with elevated ferritin and normal hemoglobin, as this risks hepatic iron accumulation and worsening liver injury 1.
Do not attribute all ferritin elevation to inflammation alone without excluding iron overload disorders, particularly if ferritin remains elevated after inflammation resolves 2.
Do not restart Wegovy without complete LFT normalization and careful risk-benefit assessment, as rechallenging with the offending agent risks severe hepatotoxicity 1.
Do not delay ultrasound imaging in progressive cholestatic patterns, as structural causes (biliary obstruction, infiltrative disease) require urgent identification 1.
Ferritin levels correlate poorly with LFTs in isolation but when combined with elevated liver enzymes suggest more severe hepatic insulin resistance and potential steatosis 3.