Liver Fibrosis Assessed by Transient Elastography in Adult Thalassemia Intermedia Patients
Authors: Fasulo Maria Rosaria , Fraquelli Mirella , Cesaretti Claudia , Rigamonti Cristina , Cassinerio Elena , Zanaboni Laura , Cappellini Maria Domenica 
Published: April 2020

Abstract
Concomitant HCV infection and iron overload are responsible for increased risk of chronic liver disease (CLD) in thalassemic patients. Liver biopsy remains so far the gold standard to assess histological activity and iron burden, although it is an invasive method poorly accepted by patients and it can not be repeated regularly. MRI ferriscan is a good tool recently introduced to estimate hepatic and cardiac iron load but it does not allow to evaluate the tissue liver damage. Transient Elastography (TE) is a new non-invasive device that measures liver stiffness (LSM) and assesses liver damage, namely fibrosis and cirrhosis. TE use in thalassemic patients is still limited, thus the aim of this study was to evaluate LSM by TE in a cohort of adults affected by Thalassemia Intermedia (TI) in order to assess the liver damage. Ninety consecutive TI patients followed at a single Italian tertiary Thalassemia Care Center in Milan were enrolled in this study. Eighteen patients (20%) were regularly transfused, 28 (31%) occasionally transfused, 44 (49%) never transfused. No one patient was on regular chelation treatment.
Table 1 summarizes the demographic, clinical and laboratory features at time of TE evaluation.
Males n° (%) 43 (47.8%) LDH U/l * 570±296 *Mean ± SD TE (FibroScan®) was performed according to Fraquelli et al. and was expressed in KPa. Only the examination with at least 10 validated measurements, a success rate greater than 60% and the interquartile range of all validated measurements lower than 30% of the mean value were considered reliable. TE cut-off to diagnose different stages of hepatic fibrosis was &gt;7.9 kPa for F&gt;2, &gt;10.3 for F&gt;3 and &gt;11.9 for F&gt;4 (cirrhosis). Forty-eight patients underwent T2* Magnetic Resonance Imaging (MRI) in order to estimate liver iron concentration (LIC). Forty-three patients (48%) had normal TE values (TE≤5.0 KPa), 35 (39%) had F&gt;1 (5.0&lt;TE≤7.9 KPa), 5 (6%) had F&gt;2, 2 (2%) had F&gt;3, 5 (6%) had F&gt;4. Mean ± SD TE value was 6.0±2.8 KPa. A significant correlation (p&lt;0.05) was observed between LSM and age (p&lt;0.001), transfusion regimen (p=0.017), serum ferritin (p=0.006), AST (p&lt;0.001), ALT (p&lt;0.001), GGT (p=0.003), bilirubin (p=0.003), albumin (p=0.017), IgG (p=0.006) and HCV positivity (HCV-Ab p&lt;0.001; HCV-RNA p=0.028). AGE yrs * 40.5±11.1 BILIRUBIN (tot) mg/dl * 2.8±1.8 BMI kg/m2 * 21.8±2.9 BILIRUBIN (conj) mg/dl * 0.5±0.3 Hb g/dl * 8.9±1.3 ALBUMIN g/dl * 4.6±0.3 FERRITIN LEVELS ng/ml* 730±690 IgG mg/dl * 1611±543 AST U/l * 32±17 SPLENECTOMY n° (%) 49 (54.4%) ALT U/l * 29±22 CHOLECYSTECTOMY n° (%) 38 (42.2%) ALP U/l * 72±25 HCV-Ab + n° (%) 18 (20.0%) GGT U/l * 24±23 HCV-RNA + n° (%) 8 (8.8%) CHE U/l * 5617±1664 LIC mg Fe/g dry weight * 7.37±5.03
Table 2 describes TE results based on transfusion regimen, ferritin levels and HCV-RNA positivity.
TE (mean ± SD) Transfusion regimen Never 5.4±2.2 Occasionally 6.4±3.5 Regular 7.2±2.9 Ferritin levels ng/ml &lt;500 5.4±2.9 500–1000 5.5±2.8 &gt;1000 8.2±3.4 HCV-RNA Positive 7.7±2.9 Negative 5.9±2.8
Moreover, splenectomy (p=0.014) and cholecystectomy (p&lt;0.001) positively correlated with TE values. No significant correlations were found between TE values and sex, BMI, Hb, ALP, LDH, CHE and LIC by MRI. This study showed that fibrosis is common in TI patients and relates with iron load estimated by ferritin and with HCV positivity. Liver fibrosis can progress to cirrhosis and eventually to liver cancer, thus TE is a reliable non-invasive method for assessing liver fibrosis and for monitoring its progression in TI patients. It is advisable to introduce TE in the follow-up of thalassemic patients, although its role as a surrogate of liver biopsy remains to be established. The relationship between LSM and LIC measured by T2* MRI needs further investigations.