Changes in mood states and biomarkers during peginterferon and ribavirin treatment of chronic hepatitis C

Abstract

Objective: Depression is a frequent side effect of interferon therapy in patients with chronic hepatitis C (CHC). The aim of this study was to identify baseline and on-treatment predictors of depression in CHC patients receiving peginterferon and ribavirin.

Methods: In total, 201 prior nonresponders with advanced fibrosis were treated with peginterferon alfa-2a and ribavirin for 24 wk in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial. Of these, 74 continued on antiviral therapy through week 48. Mood states were assessed with the Beck Depression Inventory II and the Composite International Diagnostic Interview. Plasma cortisol and whole blood serotonin levels were measured in 101 subjects at weeks 0, 4, 24, 48, and 72.

Results: The incidence of interferon-induced depression was 23% and 42% at weeks 24 and 48, respectively. Although 22% of patients had baseline depression, the absence of a week 20 virological response was the only independent predictor of interferon-induced depression at week 24 (P = 0.0009). Plasma cortisol levels did not change during treatment nor correlate with depression. In contrast, whole blood serotonin/platelet levels significantly decreased during treatment, but did not correlate with interferon-induced depression through week 24 (P = 0.35), nor through week 48 (P = 0.51).

Conclusion: Depression during peginterferon and ribavirin therapy was associated with a lower antiviral response. The significant reduction in whole blood serotonin levels over time suggest that further studies of the serotonergic pathway are warranted to identify the mediators of interferon-induced depression.

Figure 1

Interferon-induced depression through week 24 in 201 HALT-C patients. The incidence of interferon-induced depression increased to 23% by week 24. However, the incidence of interferon-induced depression was not significantly different in the 51 subjects with baseline depression compared to the 150 subjects without baseline depression (Hazard ratio = 1.47, 95% CI: 0.79, 2.73, p= 0.22).

Figure 2

Interferon- induced depression through week 48 in 74 HALT-C patients. The incidence of interferon-induced depression continued to increase from 9% at week 24 to 42% at week 48.

Figure 3

Morning plasma cortisol levels through week 24 in 101 HALT-C patients. There was no significant change in the mean plasma cortisol levels over time (p =0.60). Values plotted as mean +/− standard error.

Figure 4

Normalized whole blood serotonin levels through week 24 in 101 HALT-C patients. The y-axis value was determined by dividing the whole blood serotonin level by the platelet count at each time point and is reported as the mean +/− standard error. The mean whole blood serotonin/platelet level did significantly decline during antiviral therapy (p < 0.0001)