How to manage a patient with elevated ferritin, abnormal LFTs, and knee pain on multiple medications?

Management of Elevated Ferritin and Abnormal LFTs in a Patient on Multiple Medications

The elevated ferritin (380 μg/L) is most likely secondary to acute knee inflammation rather than iron overload, and the abnormal LFTs showing a mixed hepatocellular/obstructive pattern require immediate medication review with strong suspicion for drug-induced liver injury, particularly from recent Wegovy use or chronic omeprazole therapy. 1, 2

Ferritin Elevation Assessment

This ferritin level does not warrant iron overload workup or treatment at this time. The key distinguishing features are:

• Ferritin of 380 μg/L is only mildly elevated and well below the threshold (>1000 μg/L) that typically indicates true iron overload or requires specialist referral 1, 3, 4
• The temporal relationship with acute knee inflammation (pain 8-10/10, ongoing inflammation confirmed by specialist) strongly suggests this is a reactive elevation, as ferritin is an acute-phase reactant 5, 6, 7
• Transferrin saturation should be measured to definitively distinguish between inflammatory hyperferritinemia versus true iron overload - if <20%, this confirms anemia of chronic disease/inflammation; if >45%, consider iron overload 1, 2, 3
• The patient is already on iron supplementation (Ferograd) which should be discontinued immediately, as there is no evidence of iron deficiency and supplementation could worsen any underlying iron overload 1, 2

Monitoring Plan for Ferritin

• Repeat ferritin with transferrin saturation in 6-8 weeks after knee inflammation resolves 1
• If ferritin remains >1000 μg/L on repeat testing, refer to gastroenterology or hematology for HFE gene testing and further evaluation 3, 4

Abnormal Liver Function Tests - Priority Management

The mixed hepatocellular/obstructive pattern (ALT 154, ALP 139, GGT 102) represents a significant change from baseline and requires urgent medication review. 2

Immediate Actions Required

Stop Ferograd immediately - iron supplementation is contraindicated with elevated ferritin and can contribute to hepatotoxicity 1, 2

Review Wegovy (semaglutide) as primary suspect:

• The patient missed this week's dose, suggesting recent use
• GLP-1 agonists can cause hepatobiliary injury
• The mixed pattern with elevated GGT suggests possible biliary involvement
• Consider holding Wegovy pending LFT improvement 2

Evaluate omeprazole 40mg daily:

• Long-term PPI use at high doses can cause hepatotoxicity
• Consider de-escalation to 20mg or switching to H2-blocker if indication permits 2

Assess allopurinol contribution:

• Although less likely given stable use, allopurinol can cause hepatotoxicity
• Current uric acid control is excellent (0.24, target <0.36), allowing potential dose reduction if needed 8

Hepatotoxicity Workup

Order comprehensive hepatitis panel:

• Hepatitis A, B, C serologies
• Autoimmune markers (ANA, anti-smooth muscle antibody, anti-mitochondrial antibody)
• Ceruloplasmin if age <40 years (Wilson's disease)
• Alpha-1 antitrypsin level 2, 9

Obtain right upper quadrant ultrasound to evaluate for:

• Fatty liver disease (given weight loss medication use)
• Biliary obstruction
• Hepatic masses 2, 9

Repeat LFTs in 2-4 weeks after medication adjustments to assess for improvement 2

LFT Monitoring Algorithm

• If LFTs improve after stopping Ferograd/adjusting Wegovy: likely drug-induced liver injury, continue monitoring monthly until normalization 2
• If LFTs worsen or fail to improve: urgent hepatology referral for possible liver biopsy 2, 9
• If ALT rises >3x upper limit normal or bilirubin becomes elevated: immediate hepatology consultation 2

Knee Pain Management

Continue conservative management as directed by specialist with 6-8 weeks rest from prolonged standing 8

• The ongoing inflammation explains the ferritin elevation 5, 6
• Cycling for muscle strengthening is appropriate as it avoids weight-bearing stress 8
• Medical certificate for work modification is justified given specialist recommendation and pain severity 8
• Follow up with specialist as scheduled to reassess inflammation 8

Medication Optimization

Current regimen requires the following adjustments:

1. STOP Ferograd - no indication with elevated ferritin, potential hepatotoxin 1, 2
2. HOLD Wegovy - reassess after LFT improvement, consider reintroduction at lower dose if LFTs normalize 2
3. Reduce omeprazole to 20mg daily or switch to H2-blocker - minimize hepatotoxicity risk from high-dose PPI 2
4. Continue allopurinol 300mg - excellent uric acid control, no changes needed unless LFTs worsen 8
5. Continue antihypertensives - no hepatotoxicity concerns with metoprolol/losartan 2
6. Continue colchicine 0.5mg BD - appropriate for gout prophylaxis, monitor renal function (eGFR 68) 8

Critical Pitfalls to Avoid

• Do not assume elevated ferritin equals iron overload - it is an acute-phase reactant elevated in inflammation, infection, malignancy, and liver disease 5, 6, 7
• Do not continue iron supplementation with elevated ferritin without documented iron deficiency (low transferrin saturation) 1, 2
• Do not ignore the mixed hepatocellular/obstructive pattern - this represents significant hepatobiliary injury requiring investigation 2
• Do not attribute all findings to inflammation alone - the LFT pattern change from baseline warrants thorough drug-induced liver injury evaluation 2, 7