Genotype in Patients with Thalassemia Major Has No Impact on Risk of Liver Fibrosis

Introduction and Objectives: Patients with Thalassemia Major (TM) develop various complications related to iron overload and transfusion associated infections. It is unknown as yet if the specific genotype leading to TM has further impact on the development of liver fibrosis. Therefore, we planned to assess the impact of genotypes in patients with TM on the risk of liver fibrosis.

Methods: We included 88 patients with TM with available genotyping data in this study. These patients were followed and transfused in a single tertiary academic center. All those patients had their liver fibrosis assessed by ultrasound elastography (FibroScan device) with a cut off value of 7.8 kPa. The genotyping was done using Amplification Refractory Mutation System (ARMS)-hot start-polymerase chain reaction (PCR) technique. Iron overload was assessed using the average serum ferritin in the 5 years prior to the liver fibrosis assessment. Association was assessed using Chi-squared test and adjustment using multivariable logistic regression.

Results: A total of 88 patients were included with a median age of 27 years (Interquartile range [IQR]: 23-31). Females constituted 54% of patients and 34% of patients were splenectomised. The median alanine transaminase, aspartate transaminase, albumin and total bilirubin were 31 U/L (IQR: 20-58), 30 U/L (IQR: 18-46), 46 g/L (IQR: 43-48) and 23 µmol/L (IQR: 15-34) respectively. The median ferritin and liver iron concentration assessed by MRI T2* were 1472 µg/L (IQR: 741-2760) and 7.0 mg/gdw (IQR: 3.5-15.9) respectively. Thirty seven percent of patients had positive serology for HCV while 1% of patients had positive serology for HBV. The genotypes seen in this study included homozygous IVS-I, 5 (G-C) in 39 patients, homozygous codon 44 (-C) in 19 patients, double heterozygous IVS-I, 5 (G-C)/25 bp deletion in 5 patients and others (≤ 3 patients each) in 25 patients. The proportion of patients with fibrosis was 55%. The proportion of patients with fibrosis in the homozygous IVS-I, 5 (G-C) group was 58% compared to 52% in all other genotypes and the difference was not statistically significant (odds ratio of 1.3 with a p value of 0.6652). The impact of the genotype remained non-significant after adjustment of iron overload in the multivariable logistic regression model. The only statistically significant factor was the iron overload (p values: iron overload 0.006, genotype 0.966).

Conclusion: The risk of liver fibrosis is associated with the iron overload in patients with TM. There is no additional independent impact of the genotype. Further studies with larger sample size to study the impact of various genotypes are required to confirm these results.