Sickle Cell Disease The clinical manifestations of sickle cell disease include pain due to episodic vascular occlusions resulting in ischemic tissue damage. These occlusions occur because of changes in red blood cell deformability and fragility, increases in blood viscosity with blockage of small blood vessels, red blood cell membrane changes contributing to hemoglobin polymerization, and other effects

Patients with congenital diseases that cause hemolytic anemia, including thalassemia and sickle-cell disease, have an elevated rate of hepatitis C, often due to transfusions received before routine HCV blood screening was available. However, it can be a challenge to treat such individuals using standard hepatitis C therapy, since ribavirin can worsen anemia, and omitting ribavirin increases the risk of HCV relapse after therapy.

In a study presented at the recent Digestive Disease Week 2006 conference in Los Angeles, researchers sought to determine whether patients with congenital anemia diseases could be effectively treated for hepatitis C, despite the traditional view that ribavirin is contraindicated for this population.

The study included 10 chronic hepatitis C patients (mean age 27 years; 80% with genotypes 1 or 4); 5 had sickle-cell disease (4 HCV treatment-naïve and 1 prior non-responder) and 5 had thalassemia major (1 HCV treatment-naïve and 4 non-responders). All patients with sickle-cell disease had a METAVIR fibrosis score of F2 or less, but 4 out of the 5 thalassemia patients had cirrhosis (stage F4).

Eight patients (5 with sickle-cell disease, 3 with thalassemia) were treated with pegylated interferon plus ribavirin, while the remaining 2 received pegylated interferon monotherapy. Pegylated interferon was given at full doses, but ribavirin was started at 400 mg daily then progressively increased until recommended weight-based doses were reached. Treatment continued for 24 or 48 weeks, depending on genotype. Blood-cell growth factors were not used, and none of the sickle-cell patients received hydroxyurea.

Results 9 out of 10 patients (90%) achieved a virological response at the end of treatment. 6 out of 10 (60%) went on to achieve sustained virological response (SVR) after treatment was completed. The sustained responders included 3 thalassemia patients, including 2 with cirrhosis. 5 of the 6 sustained responses were obtained with combination therapy (for an SVR rate of 62.5%), and 1 with pegylated interferon monotherapy. During therapy, thalassemia patients required 22% more blood transfusions than before treatment. No sickle-cell patients required transfusions during or after hepatitis C treatment. The mean hemoglobin level during and at the end of treatment was actually higher than the pretreatment value among 4 out of 5 sickle-cell patients. The 6 sustained responders did not experience any liver-related complications during follow-up; 1 non-responder with thalassemia died of hepatocellular carcinoma recurrence after liver transplantation.

Conclusion

The authors noted that in this pilot study, the overall SVR was 60% despite the "unfavorable" genotypes of most patients, and that the increased transfusion requirements during treatment of patients with thalassemia are "acceptable." Given the "excellent" hematological tolerance of ribavirin observed in this study, they suggested, full-dose ribavirin plus pegylated interferon should be initiated from the start of treatment in such patients.

6/20/06

Reference
DB Ancel, D Chaslin-Ferbus, XJ Amiot, and others. Treatment of chronic hepatitis C in thalassemic and sickle cell disease patients with interferon alfa2b (IFN) and ribavirin(RBV). Abstract 198. Digestive Disease Week 2006. May 20-25, 2006. Los Angeles, CA.