Treatment of Hepatitis C Virus Infection in Thalassemia

Abstract

Treatment of hepatitis C virus (HCV) in the general population has improved over the last decade. Patients treated with peginterferon alfa (PegIFN) and ribavirin (RBV) combination therapy demonstrate overall 50-55% sustained viral response (SVR) with rates as high as 80% in patients with genotypes 2 and 3. Because RBV induces hemolysis and subsequently increases blood transfusion requirements, combination therapy has been considered contraindicated for hemoglobinopathies. This report reviews the response to interferon alfa and RBV (IFN/RBV) and PegIFN/RBV combination therapies in patients treated in the Northern California Comprehensive Thalassemia Center. A total of six thalassemia major patients were treated with IFN/RBV (n = 5; age: 4-38 years) or with PegIFN/RBV (n = 1; age: 26 years). Quantitative HCV RNA polymerase chain reaction and liver iron level assessment were completed. Transfusion volumes were obtained from patients' medical records. On IFN/RBV combination, four of five patients demonstrated SVR. The one patient on PegIFN/RBV showed end-treatment viral response after 6 months of therapy (genotype 3), but subsequently relapsed. Liver iron pretreatment level ranged from 0.2 to 22 mg/g dry weight, with a mean +/- SD of 7.9 +/- 7.7. Transfusion requirement increased by a median of 43.5% (range: 32-137%). Five of the six patients had liver iron measurements within 1 year following completion of treatment, with quantitative liver iron increasing in two patients by 2.5 mg/g dry weight, decreasing in two patients by 3 and 14 mg/g dry weight, and remaining unchanged in one patient. All patients were able to complete combination therapy, although dose reductions were required. Patients with thalassemia and high iron overload can obtain SVR after combination therapy with rates similar to those in the general population and without significant complications. Although transfusion requirements increased in most patients, iron burden was not necessarily increased.

Management of chronic viral hepatitis in patients with thalassemia: recommendations from an international panel

“…On the basis of the evidence-based data from randomized clinical trials, current treatment guidelines recommend administering this therapy for 48 weeks to patients infected by genotype 1 or 4, and for 24 weeks to patients infected by genotype 2 or 3. International guidelines recommend stopping antiviral therapy after 12 weeks in patients infected with genotype 1 or 4 if serum HCV-RNA levels have not decreased by at least 2 log units compared with baseline on the basis of strong evidence that such patients have a small likelihood of achieving sustained viral response after 48 weeks of treatment. 10 Descriptive studies [85][86][87][88][89] have reported data on small cohorts of thalassemia patients treated with ␣-interferon and ribavirin. The rate of SVR was more than 60%, but blood consumption increased during treatment by 30% to 60% because of ribavirin-associated hemolysis.…”

Treatment of interferon-α for chronic hepatitis C

“…These results showed that the PEG-IFN-α plus RBV were effective in thalassaemic patients with HCV and moderate iron overload. Patients with thalassaemia and high iron overload can obtain a SVR after combination therapy, with rates that are similar to those in the general population and without significant complications [66]. Therefore, the combination of PEG-IFN-α plus RBV in patients with thalassaemia will also become standard therapy.…”

Safety of ribavirin in adolescent thalassemic patients with chronic hepatitis C virus infection

“…[6][7][8] Butensky et al 7 treated 6 thalassemic patients with interferon, of whom only 1 patient (age 26 years) received peg-IFN plus ribavirin combination. In a recent study Harmatz et al 6 treated 21 patients of whom 16 completed the treatment.…”