Critical review of the use of erythropoietin in the treatment of anaemia during therapy for chronic hepatitis C

Abstract

Combined pegylated interferon (PegIFN) and ribavirin represents the standard therapy for patients with chronic hepatitis C (CHC), which allows for sustained viral response (SVR) in up to 90% of patients depending on certain viral and host factors. Clinical studies have demonstrated the importance of adherence to therapy, that is, the ability of patients to tolerate and sustain a fully dosed therapy regimen. Adherence is markedly impaired by treatment-related adverse effects. In particular, haemolytic anaemia often requires dose reduction or termination of ribavirin treatment, which compromises treatment efficacy. Recent evidence points to a beneficial role of recombinant erythropoietin (EPO) in alleviating ribavirin-induced anaemia thereby improving quality of life, enabling higher ribavirin dosage and consequently improving SVR. However, no general consensus exists regarding the use of EPO for specific indications: its optimal dosing, treatment benefits and potential risks or cost efficiency. The Swiss Association for the Study of the Liver (SASL) has therefore organized an expert meeting to critically review and discuss the current evidence and to phrase recommendations for clinical practice. A consensus was reached recommending the use of EPO for patients infected with viral genotype 1 developing significant anaemia below 100 g/L haemoglobin and a haematocrit of <30% during standard therapy to improve quality of life and sustain optimal ribavirin dose. However, the evidence supporting its use in patients with pre-existing anaemia, non-1 viral genotypes, a former relapse or nonresponse, liver transplant recipients and cardiovascular or pulmonary disease is considered insufficient.

The Application and Mechanism of Action of Ribavirin in Therapy of Hepatitis C

“…Dose modification for anaemia was required in 9–15% of subjects in the two Phase III registration trials of pegylated interferon and ribavirin [44,63]. Use of erythrocyte stimulating agents, such as erythropoietin and darbepoietin, have been used to counter the anaemia associated with pegylated interferon and ribavirin [64] Although the use of growth factors improves a patient’s sense of well-being and reduces the requirement for ribavirin dose reduction, it has not been consistently shown to improve SVR rates [65,66]. These agents are not approved for use in patients with chronic hepatitis C.…”

Mechanism of Erythropoietin Regulation by Angiotensin II

“…EPO is primarily produced in adult kidney, but the liver is also a source of EPO in the fetus and prenatal stages of development (Eckardt and Kurtz, 2005). Recombinant human EPO is a clinically significant drug used for the restoration of hemoglobin and red blood cell levels in anemia from a variety of causes, including chronic kidney disease, kidney failure, cancer or cancer therapy, AIDS, hepatitis C, congestive heart failure, and some surgical settings (Fisher, 2003;Jelkmann, 2007;Silverberg et al, 2010;Stickel et al, 2012). The worldwide therapeutic market for recombinant human EPO for patient treatment was reported to be ∼$6 billion USD/yr between 2006 and 2010 (Lee et al, 2012).…”

Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir: A Review in Chronic HCV Genotype 1 Infection

“…an undetectable HCV RNA level 12 or 24 weeks post-treatment) [2,5]. For years, the standard treatment has been combined use of pegylated interferon and ribavirin (hereafter pegIFN-ribavirin), which has SVR rates of only 40-50 % among genotype 1-infected patients [2] and can be poorly tolerated (particularly haematologically, sometimes necessitating erythropoietin use [6]), largely because of the interferon component [7]. However, HCV therapy has since been revolutionized by drugs that directly target proteins involved in replication of the virus.…”