Assessment of Liver Fibrosis by Transient Elastography in Children and Young Adults with Sickle Cell Disease With and Without Iron Overload

Objectives: Transfusion-associated iron overload may cause liver fibrosis. We compared transient elastography (TE) and aspartate aminotransferase-platelet ratio index (APRI), non-invasive markers for hepatic fibrosis, to percutaneous liver biopsy in children and young adults with sickle cell disease (SCD). Methods: Subjects had serum ferritin was >500 ng/mL and lacked history of viral hepatitis. APRI scores, FerriScan® R2-MRI, liver biopsies, and TEs were obtained. Hepatic fibrosis was scored according to Metavir system. Age-matched controls with SCD but without iron overload were enrolled for APRI and TE assessments. Results: Nineteen subjects (cases: 12 males, 7 females), ages 10-21 years (mean 15.9 years), were transfused an average of 9.67 years, had a mean serum ferritin of 4,899±2849 ng/mL (range 693-11,604 ng/mL), and a liver iron concentration (LIC) of 8.46±3.95 mg/g dry liver weight by R2-MRI. Mean APRI was 0.33±0.13 (0.13-0.61) in cases and 0.27±0.10 in five controls. The mean liver stiffness measures (LSM) in cases, assessed by TE, was 8.46±3.95 kPa, ranging from 3.5-14.6 kPa (expected normal less than 7 kPa). Controls had a mean LSM of 5.72±1.74 kPa (4.6-8.7 kPa). Comparison of LSM to histological fibrosis for cases revealed a T-value of 6.94, p<0.0001. There was no significant correlation between APRI and histological fibrosis and between LSM and APRI or LSM and ferritin. Conclusion: TE measures but not APRI significantly correlated with histologic fibrosis. Although the small sample size limits generalization, LSM > 10 kPa suggests liver fibrosis in children and young adults with SCD and may merit histologic confirmation especially if persistent.