A Phase I Dose Escalation Study Demonstrates Quercetin Safety and Explores Potential for Bioflavonoid Antivirals in Patients with Chronic Hepatitis C

Abstract

The hepatitis C virus (HCV) infects more than 180 million people worldwide, with long-term consequences including liver failure and hepatocellular carcinoma. Quercetin bioflavonoids can decrease HCV production in tissue culture, in part through inhibition of heat shock proteins. If quercetin demonstrates safety and antiviral activity in patients, then it could be developed into an inexpensive HCV treatment for third world countries or other affected populations that lack financial means to cover the cost of mainstream antivirals. A phase 1 dose escalation study was performed to evaluate the safety of quercetin in 30 untreated patients with chronic HCV infection and to preliminarily characterize quercetin's potential in suppressing viral load and/or liver injury. Quercetin displayed safety in all trial participants. Additionally, 8 patients showed a "clinically meaningful" 0.41-log viral load decrease. There was a positive correlation (r = 0.41, p = 0.03) indicating a tendency for HCV decrease in patients with a lower ratio of plasma quercetin relative to dose. No significant changes in aspartate transaminase and alanine transaminase were detected. In conclusion, quercetin exhibited safety (up to 5 g daily) and there was a potential for antiviral activity in some hepatitis C patients.

Trial registration: ClinicalTrials.gov NCT01438320.

Keywords: bioflavonoids; dose escalation; hepatitis C; phase I; phytomedicine; quercetin.

Conflict of interest statement

Conflict of Interest

All authors have nothing to disclose.

Copyright © 2015 John Wiley & Sons, Ltd.

Figures

Figure 1

(A) ALT change (week 4). Change in ALT (week 4 minus baseline) by dose. Reference line: ±2 SD. (B) AST Change (week 4). Change in AST (week 4 minus baseline) by dose. Reference line: ±2 SD. This figure is available in colour online at wileyonlinelibrary.com/journal/ptr.

Figure 2

(A) Viral load change (Week 2). Fold change in HCV load (week 2 compared with baseline) by dose. Reference lines: ±2.6 fold (±0.41-log). (B) Viral load change (Week 4). Fold change in HCV load (week 4 compared with baseline) by dose. Reference lines: ±2.6 fold (±0.41-log). This figure is available in colour online at wileyonlinelibrary.com/journal/ptr.

Figure 3

Quercetin dose curve. Scatterplot of quercetin plasma level at week 4 and quercetin dose with local regression line. X = patients at week 4 who displayed at least a 0.41-log (2.6 fold) viral load decrease. This figure is available in colour online at wileyonlinelibrary.com/journal/ptr.

Figure 4

Viral load and plasma quercetin relative to dose. Scatterplot of percent increase in HCV load and quercetin ratio, defined as ratio of week 4 plasma quercetin (μg/L) to dose (mg), with local regression line. Two patients with outlying values omitted (Patients 17 and 32). X = patients at week 4 who displayed at least a 0.41-log (2.6 fold) viral load decrease.

Figure 5

Hypothesized antiviral mechanism.