What is the recommended course of action for a patient with elevated iron, gamma-glutamyl transferase (Gamma GT), aspartate aminotransferase (AST), and creatine kinase (CK) levels, as well as impaired renal function and hyperlipidemia?

Management of Elevated Iron, Liver Enzymes, and Creatine Kinase

This patient requires immediate evaluation for hemochromatosis with repeat iron studies and HFE genetic testing, discontinuation of any statin therapy if present, and close monitoring of liver and muscle enzymes within 2-5 days. 1, 2

Critical Abnormalities Requiring Action

Iron Overload Assessment

• Iron saturation of 59% (reference 13-45%) with elevated iron (35.7 μmol/L, reference 10.6-33.8) strongly suggests iron overload and requires confirmatory testing. 1
• The AASLD guidelines specify that patients with persistently elevated ferritin and transferrin saturation >45% may have iron overload, and these tests should be repeated for confirmation. 1
• HFE mutation analysis should be performed immediately given the elevated transferrin saturation ≥45%. 1
• If C282Y homozygosity is confirmed and ferritin remains elevated on repeat testing, therapeutic phlebotomy should be initiated. 1

Elevated Creatine Kinase (559 U/L, reference <165)

• The markedly elevated CK (3.4× upper limit of normal) requires immediate evaluation for statin-induced rhabdomyolysis if the patient is on statin therapy. 1, 3
• AST elevation (46 U/L, slightly above 36) in conjunction with elevated CK is positively associated with peak CK levels and severity of rhabdomyolysis (P=0.002). 3
• If on statin therapy, discontinue immediately and repeat CK, AST, ALT, and creatinine within 2-3 days. 1, 2
• The 2018 AHA/ACC guidelines recommend measuring CK in cases of severe statin-associated muscle symptoms and objective muscle weakness. 1

Liver Enzyme Abnormalities

Gamma-GT (65 U/L, at upper limit of normal) and AST (46 U/L, above 36):

• Repeat ALT, AST, alkaline phosphatase, GGT, and total/direct bilirubin within 2-5 days to confirm abnormalities. 2, 4
• The mildly elevated AST (<2× ULN) with borderline GGT requires investigation but is not immediately concerning for severe liver injury. 2
• Atorvastatin can cause isolated GGT elevation (up to 6-fold) without hyperbilirubinemia or significant transaminase elevation. 5

Diagnostic Workup Priority

Immediate Testing (Within 2-5 Days):

1. Repeat iron studies (iron, transferrin saturation, ferritin) for confirmation 1
2. HFE genetic testing (C282Y and H63D mutations) 1
3. Repeat CK, AST, ALT, ALP, GGT, total and direct bilirubin 2, 4
4. Comprehensive metabolic panel including creatinine 2

Additional Evaluation:

• Viral hepatitis serologies (HBsAg, anti-HCV) to rule out viral causes 4
• Abdominal ultrasound to evaluate for hepatic steatosis and structural abnormalities 4
• Medication review for hepatotoxic or myotoxic drugs 2, 4
• Assess for metabolic risk factors (obesity, diabetes, hyperlipidemia) suggesting NAFLD 2, 4

Management Algorithm

If Statin Therapy Present:

1. Discontinue statin immediately given CK elevation >3× ULN 1
2. Monitor for symptoms of muscle weakness, dark urine, or decreased urine output 1
3. Repeat CK every 2-3 days until declining 1
4. The benefits of statin therapy do not outweigh risks when CK is significantly elevated with muscle symptoms 1

Iron Overload Management:

• If HFE testing confirms C282Y homozygosity with elevated ferritin on repeat testing, initiate therapeutic phlebotomy 1
• Target ferritin <50-100 μg/L through weekly phlebotomy initially 1
• The AASLD guidelines indicate that serum ferritin >1000 μg/L with elevated aminotransferases predicts cirrhosis in 80% of C282Y homozygotes, though this patient's ferritin level is not provided 1

Liver Enzyme Management:

• For AST <3× ULN and GGT at borderline elevation, repeat testing in 2-5 days is appropriate 2
• If values remain stable or improve, continue monitoring every 2-4 weeks until normalized 2
• The AST/ALT ratio can help differentiate causes: ratio <1.0 suggests viral hepatitis, NAFLD, or drug-induced liver injury 2

Renal Function Consideration

• The eGFR of 99 mL/min/1.73m² is normal and does not require immediate intervention 1
• However, monitor creatinine closely given elevated CK, as rhabdomyolysis can cause acute kidney injury 1
• The patient's creatinine of 82 μmol/L is within normal range (45-110) 1

Hyperlipidemia Management

• LDL cholesterol of 2.22 mmol/L is above the optimal target of ≤2.00 mmol/L for intermediate/high-risk individuals 1
• Given the elevated CK, if statin therapy is discontinued, consider alternative lipid-lowering strategies after CK normalizes 1
• Non-statin therapies (ezetimibe, PCSK9 inhibitors) should be considered if statin rechallenge fails 1

Critical Pitfalls to Avoid

• Do not attribute isolated AST elevation to cardiac causes without elevated troponin or clinical cardiac symptoms 6
• Do not delay HFE genetic testing when transferrin saturation is ≥45% 1
• Do not continue statin therapy with CK >3× ULN and elevated AST 1, 3
• Do not assume GGT elevation is solely from alcohol without considering medication effects 5
• AST can be elevated from muscle injury (given elevated CK), not just liver disease 3, 7

Follow-Up Timeline

• 2-3 days: Repeat CK, liver enzymes, iron studies 2, 4
• 1-2 weeks: Review HFE genetic testing results 1
• 2-4 weeks: Repeat monitoring if initial values stable 2
• Refer to hepatology if transaminases remain elevated for 6 months or evidence of synthetic dysfunction develops 4