Liver Fibrosis in Adult Thalassemia Patients Assessed by Transient Elastography.
Authors: Cassinerio Elena , Fraquelli Mirella , Volpato Elisabetta , Rigamonti Cristina , Colombo Massimo , Conte Dario , Cappellini Maria Domenica 
Published: April 2020

Background and aim. Transient elastography (TE) is a new, non-invasive and reproducible technique that measures liver stiffness (LSM). It has been demonstrated to be a reliable tool for assessing hepatic fibrosis and cirrhosis in patients with chronic liver disease (CLD). However, its role in patients with b- thalassemia has not been extensively investigated. The aim of the present study was to assess LSM and its possible correlation with iron overload in HCV positive patients with b- thalassemia major and intermedia.

Methods. During a six-month period (from January to June 2007) 46 consecutive adults patients with b- thalassemia afferring to a single Italian Thalassemia Care Center in Milan, Italy, were enrolled in the study. Twenty-nine patients (Group I: 7 M and 23 F; mean age 31±SD 7.1 yrs; mean BMI 23.4±SD 3 Kg/m2) had b- thalassemia major and 17 intermedia (Group II: 10 M and 7 F; mean age 43±SD12.4 yrs; BMI 22 ±SD 3 Kg/m2). Sixteen patients (55%) in group I and two (12%) in group II were HCV RNA positive. All patients were examined by TE (FibroScan®; Echosens, Paris, France) and only the examinations with at least 10 validated measurements and a success rate of at least 60% were considered adequate. According to a previous study in CLD patients the considered TE cut off to diagnosing different stages of hepatic fibrosis were: &gt;7.9 kPa for F≥2; &gt;10.3 for ≥F3 and &gt;11.9 for F=4. Twelve patients (all in group I) also had undergone liver biopsy. Necroinflammation and fibrosis were scored by METAVIR classification; liver iron concentration (LIC, mg/gr of liver dry weight) was measured on fresh tissue cores by atomic absorption spectrometry. Twenty-five patients underwent liver iron determination by T2* Magnetic Resonance Imaging (MRI) assessment.

Results. In patients who underwent liver biopsy, LSM increased proportionally to the METAVIR stage and a significant positive correlation was observed between LSM and fibrosis stage (r=0.57, p= 0.039). Patients in group I had significantly higher values of mean LSM values (10.6± SD 9.3 kPa) and serum ferritin (SF) (1367±SD 1169 ng/mL) than those in group II (6.0± SD 3.3 kPa and 716±SD 472 ng/mL, respectively) (p&lt;0.05). In both groups LSM did not significantly correlate with age, BMI, platelets count, serum iron and iron overload measured by T2* MRI. In group I a significant positive correlation was observed betweeen LSM and SF (r=0.47, p=0.008), ALT (r=0.87, p=0.0001) and GGT levels (r=0.80, p=0.0001). Among patients with b- thalassemia major LSM values did not differ significantly between HCV RNA positive (13.0±SD 12.5 kPa) and negative patients (7.7±SD 3.3 kPa) (p=NS) as well as the proportion of patients with significant (F&gt;=2) or severe fibrosis (F&gt;=3) did not differ significantly according to HCV viremic status.

Conclusion TE is a reliable non invasive technique to stage liver fibrosis in patients with b- thalassemia major. In these patients with concomitant HCV infection a significant or severe fibrosis was observed in about one third of the cases. Apart from fibrosis also serum necroinflammatory activity, GGT levels and SF levels may influence LSM values. The reliability of liver iron overload by T2* MRI evaluation remains still to be validated.