Homeostasis model assessment of insulin resistance does not seem to predict response to telaprevir in chronic hepatitis C in the REALIZE trial

Zobair Younossi, Francesco Negro, Lawrence Serfaty, Stanislas Pol, Moises Diago, Stefan Zeuzem, Pietro Andreone, Eric J. Lawitz, Stuart Roberts, Roberto Focaccia, Graham R. Foster, Andrzej Horban, Isabelle Lonjon-Domanec, Bruce Coate, Ralph Demasi, Gaston Picchio, James Witek

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21 Scopus citations

Abstract

Baseline homeostasis model assessment-estimated insulin resistance (HOMA-IR), a marker for insulin resistance, has been associated with poor virologic response to peginterferon alpha/ribavirin (PR) in chronic hepatitis C. We evaluated the association between baseline HOMA-IR and pretreatment factors on sustained virologic response (SVR) to telaprevir (TVR) in genotype 1 patients with hepatitis C and prior peginterferon/ribavirin (PR) treatment failure. Patients were randomized to 12 weeks of TVR (750 mg q8h) plus peginterferon (180 μg/week) and ribavirin (1,000-1,200 mg/day) (with or without a 4-week lead-in) followed by PR, or PR alone (PR48), for 48 weeks. Univariate and multiple logistic regression analyses explored the prognostic significance of baseline HOMA-IR alone and adjusted for other pretreatment factors and SVR. The TVR arms were pooled for the purposes of this analysis. In all, 662 patients were randomized; 578 had baseline HOMA-IR and other prognostic data and were included in this analysis. Median baseline HOMA-IR was 2.6 (interquartile range [IQR] 1.7-4.3); 207 (36%), 206 (36%), and 165 (29%) patients had baseline HOMA-IR <2, 2 to <4, and ≥4, respectively. Male gender, higher body mass index, triglycerides, gamma-glutamyl transpeptidase, maximum alanine aminotransferase/aspartate aminotransferase, and fibrosis stage were associated with higher baseline HOMA-IR. Baseline HOMA-IR was associated with SVR in univariate analysis, but not after adjustment for other baseline prognostic factors (TVR: OR=0.95, 95% confidence interval [CI]: 0.71,1.29; PR48: 0.60; 95% CI: 0.25,1.43). Conclusion: In patients with prior PR treatment failure, baseline HOMA-IR correlated with SVR in univariate but not multivariate analyses, suggesting other factors have a more direct causal relationship with virologic response to TVR-based therapy than HOMA-IR.

Original languageEnglish (US)
Pages (from-to)1897-1906
Number of pages10
JournalHepatology
Volume58
Issue number6
DOIs
StatePublished - Dec 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology

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    Younossi, Z., Negro, F., Serfaty, L., Pol, S., Diago, M., Zeuzem, S., Andreone, P., Lawitz, E. J., Roberts, S., Focaccia, R., Foster, G. R., Horban, A., Lonjon-Domanec, I., Coate, B., Demasi, R., Picchio, G., & Witek, J. (2013). Homeostasis model assessment of insulin resistance does not seem to predict response to telaprevir in chronic hepatitis C in the REALIZE trial. Hepatology, 58(6), 1897-1906. https://doi.org/10.1002/hep.26437