Dynamics of Apoptotic Activity during Antiviral Treatment of Patients with Chronic Hepatitis C

Abstract

Introduction

Cell death during antiviral therapy of patients with chronic hepatitis C is not well understood.

Methods

In the present study, apoptotic activity was monitored by quantification of apoptotic cytokeratin-18 neoepitopes in serum from patients with chronic hepatitis C before and 4, 12, 24 and 48 weeks after initiation of antiviral therapy with pegylated interferon-α2a and ribavirin and was compared with viral kinetic parameters.

Results

After 4 weeks of treatment apoptotic activity decreased significantly compared with baseline. Later during treatment, however, apoptotic activity increased again to levels similar to baseline. Alanine aminotransferase (ALT) activity also showed a significant decrease at week 4 compared with baseline but, in contrast to apoptotic activity, ALT remained at a reduced level during the treatment period. Baseline apoptotic activity was inversely correlated with the infected cell loss while an increase of apoptotic activity within the first 4 treatment weeks compared with baseline was positively correlated with the infected cell loss.

Conclusions

Apoptosis appears to be an important form of cell death during interferon-α-based treatment and is associated with infected cell loss and underestimated by ALT activity.