Can Thalassemia Cause Elevated Liver Function Tests?
Yes, thalassemia directly causes elevated liver function tests (LFTs) through iron overload-induced hepatic damage, with the severity of LFT elevation correlating exponentially with liver iron concentration, particularly when liver iron exceeds 3% dry weight. 1, 2
Mechanisms of LFT Elevation in Thalassemia
Iron Overload as the Primary Driver
Iron deposition in hepatocytes is the predominant mechanism causing elevated transaminases in thalassemia patients. The relationship between iron burden and liver damage is exponential rather than linear—hepatic fibrosis accelerates dramatically once liver iron concentration exceeds 3% dry weight. 2
- Each unit of transfused blood contains approximately 200-250 mg of iron with no physiological excretion mechanism, leading to progressive hepatic iron accumulation 3
- In thalassemia intermedia (non-transfusion-dependent), increased gastrointestinal iron absorption driven by hepcidin suppression causes intrahepatic iron overload even without transfusions 3, 4
- Serum ferritin levels >5000 ng/mL are associated with significantly elevated AST, ALT, and bilirubin compared to patients with ferritin <2500 ng/mL 1
Specific Patterns of LFT Abnormalities
ALT shows the strongest correlation with iron overload (r=0.682), followed by AST (r=0.532), with only weak correlation for bilirubin (r=0.350). 1 This pattern reflects predominantly hepatocellular injury rather than cholestatic disease.
- In thalassemia intermedia patients, ALT levels ≥63.5 U/L (3.15 times upper normal limit) correlate with liver iron concentration ≥5 mg Fe/g dry weight 5
- Patients with liver iron concentration >5 mg Fe/g dry weight demonstrate significantly higher mean ALT and AST levels 5
- The degree of transaminase elevation does not appear to be dose-related to chelation therapy itself 6
Additional Contributing Factors
Viral Hepatitis Co-infection
Chronic hepatitis C infection significantly potentiates LFT elevation in thalassemia patients beyond iron overload alone. 7
- Anti-HCV positive patients have higher mean serum ferritin, ALT, AST, and GGT levels compared to HCV-negative patients 7
- Approximately 50% of thalassemia major patients may be anti-HCV positive, with 55% of those being HCV-PCR positive 7
- HCV-positive patients typically have longer transfusion duration and higher age, compounding iron accumulation 7
Splenectomy Status
Splenectomized thalassemia patients demonstrate relatively heavier parenchymal siderosis and higher serum ferritin relative to liver iron concentration compared to non-splenectomized patients, though this does not independently affect fibrosis severity. 2
Clinical Implications for Monitoring
LFTs should be monitored every 3 months in all thalassemia patients to detect progressive liver damage and guide intensification of chelation therapy. 8
- Serum ferritin cut-offs of 916-940 ng/mL in thalassemia intermedia patients correlate with liver iron concentration >5 mg Fe/g dry weight, indicating need for chelation 5
- Liver iron concentration via MRI (not just ferritin) should guide chelation therapy intensity 8, 9
- Screen for hepatitis B and C at baseline and regularly, as chronic viral hepatitis is common in transfused patients 8, 10, 9
Common Pitfalls to Avoid
Do not attribute elevated LFTs solely to viral hepatitis without assessing iron burden—iron overload is the main leading cause of elevated liver enzymes, and HCV infection is significantly related to increased iron overload rather than being an independent cause. 7
- Deferasirox can cause drug-induced hepatitis (6% of patients develop ALT >5× ULN at two consecutive visits), requiring differentiation from iron-induced liver injury 6
- The relationship between fibrosis severity and liver iron concentration is exponential—damage accelerates rapidly above the 3% dry weight threshold, making early detection critical 2
- Hepatic fibrosis progression can be significantly retarded even with modest reductions in liver iron concentration through chelation therapy 2