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. 2013 Nov 20;8(11):e80003.
doi: 10.1371/journal.pone.0080003. eCollection 2013.

Plasma interferon-gamma-inducible protein-10 levels are associated with early, but not sustained virological response during treatment of acute or early chronic HCV infection

Jordan J Feld  1 , Jason Grebely, Gail V Matthews, Tanya Applegate, Margaret Hellard, Alana Sherker, Vera Cherepanov, Kathy Petoumenos, Barbara Yeung, John M Kaldor, Andrew R Lloyd, Gregory J Dore
Affiliations

Plasma interferon-gamma-inducible protein-10 levels are associated with early, but not sustained virological response during treatment of acute or early chronic HCV infection

Jordan J Feld et al. PLoS One. .

Abstract

Background: High plasma levels of interferon-gamma inducible protein-10 (IP-10) have been shown to be associated with impaired treatment response in chronic hepatitis C virus (HCV) infection. Whether IP-10 levels predict treatment in acute HCV infection is unknown.

Methods: Patients with acute or early chronic HCV infection from the Australian Trial in Acute Hepatitis C (ATAHC) cohort were evaluated. Baseline and on-treatment plasma IP-10 levels were measured by ELISA. IL28B genotype was determined by sequencing.

Results: Overall, 74 HCV mono-infected and 35 HIV/HCV co-infected patients were treated in ATAHC, of whom 89 were adherent to therapy and were included for analysis. IP-10 levels correlated with HCV RNA levels at baseline (r = 0.48, P<0.001) and during treatment. Baseline IP-10 levels were higher in patients who failed to achieve rapid virological response (RVR). Only one patient with a plasma IP-10 level >600 pg/mL achieved RVR. There was no association with IP-10 levels and early virological response (EVR) or sustained virological response (SVR).

Conclusions: Baseline IP-10 levels are associated with early viral kinetics but not ultimate treatment outcome in acute HCV infection. Given previous data showing that patients with high baseline IP-10 are unlikely to spontaneously clear acute HCV infection, they should be prioritized for early antiviral therapy.

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Conflict of interest statement

Competing Interests: Roche Pharmaceuticals supplied financial support for pegylated IFN-alfa-2a/ribavirin for this study. JJF is consultant/advisor and/or has received research support from Abbott, Achillion, Boehringer-Ingelheim, Gilead, Janssen, Merck, Roche and Vertex. JG is a consultant/advisor for Merck and has received research grants from Roche and Merck. GD is a consultant/advisor and has received research grants from Roche, Merck, Janssen, Gilead, Bristol Myers Squibb. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Figure 1
Figure 1. Correlation of baseline plasma IP-10 and HCV RNA titre.
The correlation between baseline plasma IP-10 level and serum HCV RNA titre was evaluated using Pearson’s correlation co-efficient.
Figure 2
Figure 2. Baseline plasma IP-10 values according to patient characteristics.
Baseline plasma IP-10 levels are shown by: a) HCV RNA above or below 400,000 IU/mL b) IL28B genotype c) HCV genotype (1 vs. non-1) d) sex e) ethnicity (Caucasian vs. other) f) HIV status and g) the presence or absence of symptoms at presentation. Mean plasma IP-10 levels were compared using the student’s t-test with Welch’s correction for unequal variances as appropriate.
Figure 3
Figure 3. Baseline plasma IP-10 according to virological responses.
Baseline IP-10 values are shown in patients who did and did not achieve: a) RVR b) EVR c) ETR and d) SVR. Results are shown for the entire treated cohort. IP-10 levels were compared using the student’s t-test with Welch’s correction for unequal variances as appropriate. RVR rapid virological response; EVR early virological response; ETR end of treatment response; SVR sustained virological response.
Figure 4
Figure 4. Baseline plasma IP-10 according to virological responses in genotype 1 patients only.
Baseline IP-10 values are shown in genotype 1 patients who did and did not achieve: a) RVR b) EVR c) ETR and d) SVR. IP-10 levels were compared using the student’s t-test with Welch’s correction for unequal variances as appropriate. RVR rapid virological response; EVR early virological response; ETR end of treatment response; SVR sustained virological response.
Figure 5
Figure 5. Response based on baseline IP-10 level above or below 150 pg/mL among adherent individuals.
The proportion of patients with baseline IP-10 levels above or below 150 pg/mL who achieved RVR, cEVR, ETR and SVR are shown for a) the whole cohort and b) patients with genotype 1 infection. Responses were compared using Fisher’s Exact Test.
Figure 6
Figure 6. Early virological decline among adherent participants with recent HCV.
The decline in HCV RNA during the first 12 weeks of treatment is shown in patients with high baseline plasma IP-10 in those with HCV monoinfection (PEG-IFN) (>150 pg/mL, circles and solid line) or HIV/HCV co-infection (PEG-IFN/ribavirin) (≥150 pg/mL, upward triangles and solid line). The HCV RNA decline is also shown for patients with low baseline plasma IP-10 levels and HCV monoinfection (<150 pg/mL, downward triangles and dotted line) or HCV/HIV co-infection (<150 pg/mL, squares and dotted line).
Figure 7
Figure 7. Proposed algorithm for incorporation of plasma IP-10 testing into clinical management of acute HCV infection.
See this image and copyright information in PMC

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