Effect of Antioxidant Therapy On Hepatic Fibrosis and Liver Iron Concentrations In Beta-Thalassemia Major Patients

Repeated blood transfusion my lead to peroxidative tissue injury in thalassemia ptients due to secondary iron overload. The aim of the study was to assess the effects of antioxidant vitamins on the oxidative stress, antioxidant status, erythrocytes, hemoglobin derivatives. Also to demonstrate their effects on hepatic status in multitransfused beta-thalassemia major

The study was a prospective follow up study. It involved thirty β-thalassemia major patients aged 4–17 years (15 males and 15 females) recruited from Hematology Oncology Department, Ain Shams University. They were compared to a 20 healthy age and sex matched subjects served as controls. Patients were treated with oral dose of vitamin E (400 mg/day if patient weight < 20 kg and 600 mg/day in patient weight at least 20 kg), low dose of vitamin C (100 mg/day) and vitamin A (25000 IU/ week) for twelve months. Investigations were performed before and after 6 and twelve months of therapy: liver transaminases, serum ferrittin, hepatitis status for HBV, HCV, hepatic fibroscan elastography (TE) for assessment of liver fibrosis and hepatic MRI R2* to measure liver iron concentration (LIC). Assessment of the oxidant /antioxidant capacity by measuring: reduced glutathione, malondialdehyde, ascorbic acid, catalase enzyme, superoxide dismutase, glutathione reductase as well as glutathione peroxidase determination.

All patients were on iron chelation therapy: 12 patients received deferiprone (DFP) (75 mg/kg per day orally), 8 patients received deferoxamine (DFO) (30–50 mg/kg per day subcutaneously at least 5 times/week), and 10 patients received a combination of DFO (30–50 mg/kg per day, 2–3 days/week) and DFP (75 mg/kg per day, 7 days/week). In the studied thalassemics 40.0% and 54% were HCV RNA and hepatitis B surface antigen positive. The basal levels of vitamin A, E and C were 3.1, 4, and 2.6 times significantly lower in thalassemia patients compared to controls(p<0.001). Malondialdehyde concentration was 3.4 times higher while reduced glutathione level was 3.2 times lower in studied thalassemics compared to controls(p=0.02,p=0.04). Levels of vitamin A, C, E, reduced glutathione and hemoglobin were significantly elevated during the study period on antioxidant therapy(P=0.03, P=0.02, P<0.001)).This was paralleled by a significant decline in the oxidative-stress marker malondialdehyde (7.87±2.2,8.2±3,11.6±4.1nmol/L;at baseline, after 6 and 12 ms therapy respectively, p<0.001) and serum ferritin levels(2887±1009,2456±1122,2114±990 μg/L, p=0.05). After twelve months of vitamins treatment, there were highly significant improvements of enzymatic antioxidants parameters as compared with before treatment in thalassemia patients. Alanine transaminase, aspartate transaminase, superoxide dismutase and glutathione peroxidase were significantly decreased(p<0.001) while catalase and glutathione reductase activities were significantly elevated(p<0.005). The extent of hemolysis of erythrocytes in studied patients decreases markedly after treatment compared to baseline (p<0.001).There was significant improvement of hepatic fibrosis after 12ms of therapy as 20% of patients had high TE values (FibroScan>12kPa) at baseline compared to 16% after 12 ms therapy (P=0.04).And 56% of patients had value of (>6kPa) at baseline compared to 66%, 70% at 6 and 12months therapy respectively(p=0.03). Levels of liver iron concentration were progressively decreased during the study period compared to baseline (22.4±6.7, 19.4±4.8, 14.4±3.6 mg/gm) in MRI R2* at baseline, after 6 and 12 months therapy respectively<0.001.

Antioxidants vitamins are effective in clinical practice for regulation of antioxidant status as well as improvement of liver iron concentration and hepatic fibrosis in multitransfused thalassemia major patients.

No relevant conflicts of interest to declare.