Early Hepatitis C Viral Response (EVR) to Peginterferon Alfa 2a and Ribavirin in Patients with β Thalassemia.

Hepatitis C virus (HCV) infection is an important cause of liver failure and death in patients with thalassemia who received frequent blood transfusions before HCV screening became routine. Severe transfusion-related iron overload may accelerate the progression of liver disease, influence response to therapy, and increase the risk of antiviral treatment in these patients. An open-label, single arm trial of peginterferon alfa 2a (180 ug weekly) and ribavirin (1200 mg/day for > 75 kg, 1000 mg/day 50 to 75 kg, 800 mg for < 50kg) was initiated in August, 2003 in the NIH-sponsored Thalassemia Clinical Trials Network to examine safety and efficacy in adult patients. Although the study is still enrolling patients, we are presenting viral response data for the first 16 patients (mean age: 33 yrs, range 22 to 44, 50% female, 75% genotype 1). Iron burden was assessed by chemical analysis of liver biopsy and HCV RNA levels were measured using the Roche COBAS HCV Tests (qualitative and quantitative). These analyses were performed by a central laboratory. HCV levels were measured at baseline, weeks 1, 2, 3, 4, 12 and 24.

Early Virologic Responses

Four patients discontinued between weeks 4 through 12 (1 death, 1 persistent cough, 1 extreme fatigue, and 1 pregnancy (spouse). These patients had all achieved > 2 log drop by week 4. The mean liver iron at baseline was 10.1 mg/gm dry wt (range: 1.1 to 21.2) and the mean log HCV RNA level was 5.8 (range 4.0 to 6.8). The median time to > 2 log decrease was 1 week for patients with genotype 2 and 4 weeks for patients with genotype 1 (p=0.004). There was no correlation either between baseline iron or baseline HCV level and time to > 2 log decrease. Transfusion requirement increased 52% as assessed at 12 weeks and did not predict earlier viral response. In summary, there is EVR (>2 log drop) in 63% at 4 weeks and 91 % at 12 weeks, comparable to those seen in patients without thalassemia. Quantitative hepatic iron concentration at baseline was not a predictor of EVR. Completion of the study is planned to determine whether the EVR predicts sustained viral response and whether the iron overload or increased transfusion requirements during therapy pose significant safety issues.