Diabetes Mellitus and Advanced Liver Fibrosis Are Risk Factors for Severe Anemia During Telaprevir-based Triple Therapy

Liver International

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Original Article

DOI: 10.1111/liv.12342

This article is protected by copyright. All rights reserved.

James F. Crismale1, Valérie Martel-Laferrière1, Kian Bichoupan1, Emily Schonfeld1, Alexis Pappas1, Christina Wyatt2, Joseph A. Odin1, Lawrence U. Liu1, Thomas D. Schiano1, Ponni V. Perumalswami1, Meena Bansal1, Douglas T. Dieterich1, Andrea D. Branch1,*

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/liv.12342

Publication History
Accepted manuscript online: 1 OCT 2013 12:35AM EST
Manuscript Accepted: 22 SEP 2013
Manuscript Revised: 14 SEP 2013
Manuscript Received: 20 MAY 2013

Keywords: hepatitis C virus; telaprevir; pegylated-interferon; ribavirin; triple therapy; anemia; diabetes mellitus

Abstract

Background

Adding telaprevir to pegylated-interferon and ribavirin increased both response rates and side effects of hepatitis C virus (HCV) treatment.

Aims

We identified variables associated with severe anemia during telaprevir-based triple therapy.

Methods

An observational study was performed on 142 HCV-infected patients between June 2011 and March 2012. All subjects completed 12 weeks of telaprevir-based triple therapy or discontinued early due to anemia. Severe anemia was defined by a hemoglobin ≤8.9 g/dL; advanced fibrosis was determined by Fib-4 ≥3.25.

Results

The 47 (33%) patients who developed severe anemia were similar to those who did not in sex, race, and prior response to dual therapy, but they were more likely to have diabetes (23.4% vs. 6.3%, p<0.01), advanced fibrosis (46.8% vs. 29.5%, p=0.04), and a history of anemia during previous dual therapy (29.7% vs. 11.4%, p=0.02). Patients developing severe anemia were older (59 vs. 56 years, p=0.02), had lower baseline platelet counts (134 vs. 163 x10⁹/L, p=0.04), hemoglobin (14.0 vs. 15.0 g/dL, p<0.01), estimated glomerular filtration rate (79 vs. 90 mL/min/1.73m², p=0.03), and a higher median ribavirin/weight ratio (14.9 vs. 13.2 mg/kg, p<0.01). In multivariable logistic regression, presence of diabetes (OR=5.61, 95%CI: 1.59-19.72), Fib-4 ≥3.25 (OR=3.09, 95%CI: 1.28-7.46), higher ribavirin/weight ratio (OR=1.31 per mg/kg, 95%CI: 1.13-1.52), and lower baseline hemoglobin (OR=0.57 per g/dL, 95%CI, 0.41-0.80) were independently associated with developing severe anemia.

Conclusions

Severe anemia occurred in one-third of patients receiving telaprevir-based triple therapy. Risk was greater in patients with diabetes, advanced liver fibrosis, higher ribavirin/weight ratio and lower baseline hemoglobin.

Source