Prognostic factors and early predictability of sustained viral response with peginterferon alfa-2a (40KD)

Abstract

Background/Aims: Baseline factors and early decline in serum hepatitis C virus RNA are predictive of sustained virological response to interferon therapy in patients with chronic hepatitis C. We evaluated the prognostic value of baseline factors and early viral RNA among patients treated with peginterferon alfa-2a (40KD).

Methods: Data were pooled from three randomized trials involving 814 patients treated with peginterferon alfa-2a (40KD) (90, 135, or 180 μg). Stepwise and multiple logistic regression identified independent baseline factors associated with response. Receiver operating characteristic curves for both absolute values and log₁₀ decline in viral RNA at 4, 8, 12 and 24 weeks of therapy were created.

Results: Independent prognostic factors for sustained virological response included viral genotype non-1, low pretreatment viral load, age (<40 years), no cirrhosis and body weight (<85 kg). In addition, alanine aminotransferase quotient (>3) and histological activity index score (>10) were also independently prognostic. Receiver operating characteristic curves showed that detectable or less than 2-log₁₀ decline in viral RNA at week 12 predicted sustained virological non-response (negative predictive value is 98%).

Conclusions: In patients with chronic hepatitis C treated with peginterferon alfa-2a (40KD), the decision to continue or stop treatment can be made as early as week 12.

Introduction

Interferon alfa (IFN)-based regimens (i.e. IFN/ribavirin and IFN monotherapy for patients who cannot tolerate ribavirin) are the standard treatment for patients with chronic hepatitis C. As these regimens produce sustained virological responses in less than half of the patients treated, and are associated with significant adverse events, identifying the patients who are likely or unlikely to respond to treatment would be desirable.

A number of baseline factors are predictive of response to treatment with IFN alone or IFN/ribavirin therapy in patients with chronic hepatitis C. Viral genotype other than type 1 is the most consistent and powerful predictor of a positive response[1], [2], [3], [4]. Other factors associated with a positive response to therapy include the absence of cirrhosis or fibrosis, age <40 years, female gender, and white race [1], [5], [6], [7].

Early antiviral response to therapy appears to be predictive of response (positive or negative) to treatment [1], [8]. Hepatitis C virus (HCV) RNA results appear to have a greater negative predictive value in hepatitis C virus early in treatment [1]. Based on these data, American [9], Canadian [10], and European [11] expert consensus conferences have recommended that patients with detectable levels of HCV RNA after 12 weeks of treatment with IFN alone should either discontinue therapy or seek an alternative therapy. In contrast, since IFN/ribavirin therapy is associated with late responses in some patients, early loss of detectable HCV RNA has less predictive value in patients receiving IFN/ribavirin therapy [12], [13]. No previous data are available regarding the predictive value of baseline factors and early viral kinetics for patients receiving pegylated interferons.

The objective of this study was to examine the baseline prognostic factors associated with sustained virological response and the predictive value of early serial HCV RNA determinations in patients treated with peginterferon alfa-2a (peginterferon alfa-2a [40KD]).