November 19, 2013

Management of anemia induced by triple therapy in patients with chronic hepatitis C: Challenges, opportunities and recommendations

Journal of Hepatology

Volume 59, Issue 6, Pages 1323-1330, December 2013

Manuel Romero-Gómez, Marina Berenguer, Esther Molina, José Luis Calleja

Received 6 May 2013; received in revised form 20 June 2013; accepted 8 July 2013. published online 17 July 2013.

The addition of protease inhibitors, boceprevir or telaprevir, to peginterferon+ribavirin (PegIFN/RBV) increases the frequency as well as the severity, and hence, clinical relevance of anemia, which has now become one of the major complications associated with triple therapy. Most significant factors associated with anemia in patients receiving triple therapy include older age, lower body mass index (BMI), advanced fibrosis, and lower baseline hemoglobin. The variability in inosine triphosphate pyrophosphatase (ITPA) gene, which encodes a protein that hydrolyses inosine triphosphate (ITP), has been identified as an essential genetic factor for anemia both in dual and triple therapy. The correct management of anemia is based on anticipation, characterization and therapeutic management. Basically, anemia can be characterized in 3 types: ferropenic (mostly in fertile women), thalassemic type hemolytic anemia, and anemia from chronic processes. Functional deficit of iron should also be excluded in patients with normal ferritin and lower saturation of transferrin. Ribavirin dose reduction and epoetin, sequentially, are indicated in the management of anemia. Epoetin non-response can be caused by lack of time, type of anemia, functional iron deficit or erythropoietin resistance. In the transplantation setting, adding a protease inhibitor to PegIFN/RBV results in a significant increase in the incidence and severity of anemia and, as a consequence, a greater need for epoetin, transfusions, and ribavirin dose reductions. Packed red cell transfusions are utilized when hemoglobin decreases to less than 7.5g/dl and/or there are clinical symptoms and/or there is no response to other therapeutic measures.

Abbreviations: BMI, body mass index, ITPA, inosine triphosphate pyrophosphatase, HCV, hepatitis C virus, GWAS, genome-wide association study, SNP, single nucleotide polymorphisms, sRfT, transferrin soluble receptor, EPO, erythropoietin

Keywords:Hepatitis C virus, Anemia, Boceprevir, Telaprevir, Pegylated interferon, Ribavirin, Epoietin, Protease inhibitor


Anemia is a major complication of antiviral therapy in chronic hepatitis C. With dual therapy, and despite its negative impact on quality of life, it was a desirable effect due to its association with higher sustained viral response rates. In patients treated with triple therapy, the impact of anemia on outcome is controversial; its incidence though is significantly higher and the management in this scenario is more complex, frequently requiring ribavirin dose reduction, epoetin and, in some cases, blood transfusions, jeopardizing the final efficacy of triple therapy.

In this review, we will try to answer the questions that physicians face regarding the management of anemia among patients treated with telaprevir or boceprevir triple therapy. We highlight the most relevant aspects with regards to the incidence of anemia, its clinical course, factors implicated in its development, characterization, and management.

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