Reply to: “Renal impairment and anemia during triple therapy”
Authors: Manuel Romero-Gómez, Marina Berenguer, Esther Molina, Jose-Luis Calleja
Journal: Journal of Hepatology (2014)

Management of anemia induced by triple therapy in patients with chronic hepatitis C: Challenges, opportunities and recommendationsJournal of HepatologyVol. 59Issue 6PreviewThe 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. Full-Text PDF Open AccessRenal impairment and anemia during triple therapyJournal of HepatologyVol. 60Issue 5PreviewWe read with great interest the recently published review by Romero-Gòmez and colleagues concerning the management of anemia induced by triple therapy in patients with chronic hepatitis C [1]. In their work, authors thoroughly discuss about pathophysiological mechanisms responsible for the anemia observed during triple therapy with telaprevir or boceprevir, remark baseline and on-treatment factors predictive of more severe anemization, and propose a sequential strategy to manage anemia based first on ribavirin dose reduction and then on epoetin administration. Full-Text PDF Open Access We appreciate the comment by Vespasiani-Gentilucci et al. about renal impairment and anemia during hepatitis C treatment with protease inhibitors. We agree with the authors that renal impairment is a growing concern in these patients, although the prevalence of estimated glomerular filtration rate (eGFR) <60 ml/min does not seem to be significantly high with these drugs (6.6% with boceprevir and 4.7% with telaprevir [[1]Mauss S. Hueppe D. Alshuth U. Renal impairment is frequent in chronic hepatitis C patients under triple therapy with telaprevir or boceprevir.Hepatology. 2014; ([Epub ahead of print])PubMed Google Scholar]). Additionally to protease inhibitors, older age, arterial hypertension, high baseline serum creatinine as well as type 2 diabetes mellitus were found to be associated with anemia [[2]Crismale J.F. Martel-Laferrière V. Bichoupan K. Schonfeld E. Pappas A. Wyatt C. et al.Diabetes mellitus and advanced liver fibrosis are risk factors for severe anaemia during telaprevir-based triple therapy.Liver Int. 2013; ([Epub ahead of print])https://doi.org/10.1111/liv.12342Crossref PubMed Scopus (7) Google Scholar]. Probably, the link between these factors and anemia is the appearance of renal impairment [[3]Hörl W.H. Anaemia management and mortality risk in chronic kidney disease.Nat Rev Nephrol. 2013; 9: 291-301Crossref PubMed Scopus (100) Google Scholar]. Indeed, the mechanisms involved in renal impairment with protease inhibitors remain poorly understood. Significant inhibition of some human renal drug transporters that could influence ribavirin serum concentration has been described with telaprevir [[4]Kunze A. Huwyler J. Camenisch G. Gutmann H. Interaction of the antiviral drug telaprevir with renal and hepatic drug transporters.Biochem Pharmacol. 2012; 84: 1096-1102Crossref PubMed Scopus (63) Google Scholar]. This has been correlated with delta eGFR [[5]Karino Y. Ozeki I. Hige S. Kimura M. Arakawa T. Nakajima T. et al.Telaprevir impairs renal function and increases blood ribavirin concentration during telaprevir/pegylated interferon/ribavirin therapy for chronic hepatitis C.J Viral Hepat. 2013; ([Epub ahead of print])https://doi.org/10.1111/jvh.12162Crossref PubMed Scopus (37) Google Scholar]. Telaprevir though has shown an acceptable tolerability in haemodialyzed patients who were listed for kidney transplantation, managing successfully anemia with erythropoietin and ribavirin dose reductions [[6]Dumortier J. Guillaud O. Gagnieu M.C. Janbon B. Juillard L. Morelon E. et al.Anti-viral triple therapy with telaprevir in haemodialysed HCV patients: is it feasible?.J Clin Virol. 2013; 56: 146-149Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar]. On the other hand, mean boceprevir concentration was comparable in patients with end-stage renal disease and in healthy subjects [[7]Treitel M. Marbury T. Preston R.A. Triantafyllou I. Feely W. O’Mara E. et al.Single-dose pharmacokinetics of boceprevir in subjects with impaired hepatic or renal function.Clin Pharmacokinet. 2012; 51: 619-628Crossref PubMed Google Scholar]. In conclusion, there is a mild risk of renal insufficiency stage 3 with protease inhibitors that could be responsible, at least in part, of the anemia that develops during triple therapy. Thus, renal function should be closely monitored to anticipate the appearance of anemia. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.