The Effect of Hepatitis C - Direct-Acting Antiviral Treatment on the Hematogical Profile of Thalassemic Patients

Background: The prevalence ofhepatitis C (HCV) infection remains high among transfusion-dependent thalassemic patients. Chronic Hepatitis C, along with iron overload toxicity, eventually leads to liver fibrosis and cirrhosis. The new direct-acting antiviral (DAA)-containing regimens have shown great efficacy in achieving sustained viral response, even in patients with advanced liver disease. The aim of this study was to investigate the impact of HCV treatment with DAA on the hematological profile and management of patients with thalassemia.

Methods: Twelve adult patients (5 males, 7 females) with age between 30 and 49 years old (mean: 43±4.5 years) were treated with interferon-free DAA-regimens in accordance to the EASL 2015 guidelines. All patients had previously, either not responded to or relapsed after treatment with interferon. Patients received various regimen schemas, with 10 of them receiving Sofosbuvir-containing regimen. Hepatitis C genotypes were: 1a (n=1), 1b (n=8), 3a (n=1), 4a (n=1) and 4h (n=1).

Hematological and biochemical profiles were assessed at -12, -9, -6, -3, -2, -1 months before the treatment initiation, monthly during treatment and at +1, +2, +3, +4 and +6 months after treatment. Patients' transfusion requirements as well as chelation therapy needs were calculated per period. To discriminate the effect on Ferritin levelsof hepatic necrosis and inflammation from iron overload, the ratios Ferritin x (ALT-1) / ALT and Ferritin/ALT were calculated and the values before and after treatment were compared (Eisuke Ozawa et al, 2011, Journal of Gastroenterology and Hepatology, 1326-1332). Paired t-test was used for statistical analysis.

Results: All patients responded well and achieved SVR. Patients' Serum Ferritin levels decreased significantly (mean± SD: 776 ± 604 ng/ml before treatment vs 449 ± 385 ng/ml, after treatment, p=0.011) in response to HCV treatment. The decrease in ferritin levels was universal in all patients (mean± SD: 327 ± 372 ng/ml, range=90 -563 ng/ml). Ferritin x (ALT-1)/ ALT ratio decreased also significantly (mean± SD: 768± 599 before treatment vs 426 ± 362, after treatment, p=0.009), whereas Ferritin/ALT ratio generally increased significantly (mean± SD: 8.5 ± 6.1 before treatment vs 23 ± 25, after treatment, p=0.03). Transfusion requirements did not change in between the three observational periods, i.e. before, during and after HCV treatment. Similarly, there were no changes in the usage of chelation therapy.

Conclusions: Treatment with DAA-containing regimens shows promising results in controlling chronic hepatis C in thalassemic patients with advanced liver disease, without having an effect in transfusion requirements. The significant drop of serum Ferritin levels in these patients may be due, at least in part, to decreased hepatic inflammation. The kinetics of serum ferritin levels during HCV treatment needs to be evaluated with caution for optimization of chelation therapy.