Dual therapy with peg-interferon and ribavirin in thalassemia major patients with chronic HCV infection: Is there still an indication?

Abstract

Background

Iron overload and hepatitis C virus (HCV) infection together can lead to chronic liver damage in thalassemia major (TM) patients.

Aims

We investigated viral, genetic, and disease factors influencing sustained virological response (SVR) after peg-interferon and ribavirin therapy in TM patients with HCV infection.

Methods

We analyzed 230 TM patients with HCV infection (mean age 36.0 ± 6.3 years; 59.1% genotype 1; 32.2% genotype 2; 3.4% genotype 3; and 5.3% genotype 4; 28.7% carried CC allele of rs12979860 in IL28B locus; 79.6% had chronic hepatitis and 20.4% cirrhosis; 63.5% naive and 36.5% previously treated with interferon alone) treated in 14 Italian centers.

Results

By multivariate regression analysis SVR was independently associated with CC allele of IL28B SNP (OR 2.98; CI 95% 1.29–6.86; p = 0.010) and rapid virologic response (OR 11.82; CI 95% 3.83–36.54; p < 0.001) in 136 genotype 1 patients. Combining favorable variables the probability of SVR ranged from 31% to 93%. In genotype 2 patients, only RVR (OR 8.61; CI 95% 2.85–26.01; p < 0.001) was associated with SVR higher than 80%. In 3 patients with cirrhosis a decompensation of liver or heart disease were observed. Over 50% of patients increased blood transfusions.

Conclusion

Dual therapy in TM patients with chronic HCV infection is efficacious in patients with the best virological, genetic and clinical predictors. Patients with cirrhosis have an increased risk of worsening liver or heart disease.

Introduction

Chronic liver disease is a common clinical issue in thalassemia major (TM) patients because iron overload and hepatitis C virus (HCV) infection together can lead to chronic liver damage [1], [2]. In young patients free of HCV infection, adequate iron chelation prevents the development of liver fibrosis, but adult patients with active HCV infection frequently have severe liver fibrosis, even when they are undergoing regular and effective iron chelation therapy [3], [4], [5] and cirrhosis due to HCV infection is a major risk for development of hepatocellular carcinoma (HCC) and liver failure [6], [7].

Antiviral therapy is indicated in TM patients with clinical evidence of significant liver fibrosis or cirrhosis [8]. The absence of cirrhosis, low iron hepatic concentration, and infection by HCV genotype other than 1b are the main clinical and virologic findings that predict a good response to therapy [9]. There is little data on the efficacy and tolerability of combination therapy with peg-interferon (PegIFN) and ribavirin (RBV) in TM patients since patients with hemoglobinopathies have been excluded from registration trials, and the addition of RBV therapy has long not been permitted in this subset of patients because of the high risk of severe hemolytic anemia [10], [11].

The primary aim of this analysis was to evaluate the efficacy and tolerability of combination therapy with Peg-IFN and RBV in a large number of TM patients with chronic HCV infection.

Secondarily, we investigated the role of HCV genotypes, single nucleotide polymorphisms (SNPs) located in and near the interleukin 28B (IL28B) locus, and iron overload on the efficacy of anti-HCV treatments. Finally, we evaluated the changes in blood transfusion regime and iron chelation therapy during the antiviral treatment.