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Multicenter Study
. 2015 Dec;22(12):1020-32.
doi: 10.1111/jvh.12429. Epub 2015 Jun 22.

Response to treatment following recently acquired hepatitis C virus infection in a multicentre collaborative cohort

J S Doyle  1   2   3 , K Deterding  4   5 , J Grebely  6 , H Wedemeyer  4   5   7 , R Sacks-Davis  1   2 , T Spelman  1 , G Matthews  6 , T M Rice  8 , M D Morris  8 , B H McGovern  9 , A Y Kim  10 , J Bruneau  11 , A R Lloyd  12 , K Page  8 , M P Manns  4   5   7 , M E Hellard  1   2   3 , G J Dore  6 ; InC3 Study Group
Affiliations
Multicenter Study

Response to treatment following recently acquired hepatitis C virus infection in a multicentre collaborative cohort

J S Doyle et al. J Viral Hepat. 2015 Dec.

Abstract

Pegylated interferon therapy is highly effective in recently acquired HCV. The optimal timing of treatment, regimen and influence of host factors remains unclear. We aimed to measure sustained virological response (SVR) during recent HCV infection and identify predictors of response. Data were from five prospective cohorts of high-risk individuals in Australia, Canada, Germany and the United States. Individuals with acute or early chronic HCV who commenced pegylated interferon therapy were included. The main outcome was SVR, and predictors were assessed using logistic regression. Among 516 with documented recent HCV infection, 237 were treated (pegylated interferon n = 161; pegylated interferon/ribavirin n = 76) (30% female, median age 35 years, 56% ever injected drugs, median duration of infection 6.2 months). Sixteen per cent (n = 38) were HIV/HCV co-infected. SVR among those with HCV mono-infection was 64% by intention to treat; SVR was 68% among HCV/HIV co-infection. Independent predictors of SVR in HCV mono-infection were duration of HCV infection (the odds of SVR declined by 8% per month of infection, aOR 0.92, 95% CI 0.85-0.99, P = 0.033), IFNL4 genotype (adjusted OR 2.27, 95% CI 1.13-4.56, P = 0.021), baseline HCV RNA <400 000 IU/mL (aOR 2.06, 95% CI 1.03-4.12, P = 0.041) and age ≥40 years (vs <30: aOR 2.92, 95% CI 1.31-6.49, P = 0.009), with no difference by drug regimen, HCV genotype, symptomatic infection or gender. The effect of infection duration on odds of SVR was greater among genotype-1 infection. Interferon-based HCV treatment is highly effective in recent HCV infection. Duration of infection, IFNL4 genotype and baseline HCV RNA levels can predict virological response and may inform clinical decision-making.

Keywords: acute infection; hepatitis C virus; recently acquired infection; virological response.

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Conflict of interest statement

Conflicts of interest:

JD, RSD, TS, TR, GM, BHM, AL, MDM, KP, MH: no conflicts of interest to declare

KD: received lecture fees and travel support from MSD

JG: is a consultant/advisor and has received research grants from Abbvie, Bristol Myers Squibb, Gilead Sciences and Merck/MSD.

HW: received honoraria for consulting or speaking from Abbott, Biolex, BMS, Gilead, ITS, Janssen-Cilag, Medigenics, Merck/Schering-Plough, Novartis, Roche, Roche Diagnostics, Siemens, Transgene, and ViiV; and research grants from Abbott, BMS, Gilead, Merck/MSD, Novartis, Roche, Roche Diagnostics, and Siemens.

AYK: is a consultant/advisor for Bristol-Myers Squibb, Abbvie Pharmaceuticals, and has received research grants from Abbvie Pharmaceuticals and Gilead Sciences

JB: received grants from Merck/MSD

MPM: received honoraria for consulting or speaking from Abbvie, Achillion, BMS, Gilead, GSK, Janssen Pharmaceuticals, Medgenics, Merck/MSD, Novartis, Roche, and Vertex; and research grants from Abbvie, BMS, Gilead, Merck, Novartis, Roche, Roche Diagnostics and Siemens.

GD: received honoraria for consulting and speaking from Roche, Merck/MSD, Janssen, Gilead, Abbvie, and Bristol-Myers Squibb; received grants from Roche, Merck/MSD, Janssen, Gilead, Abbvie and Bristol-Myers Squibb.

Figures

Figure 1
Figure 1. Treatment response rates at end of treatment (ETR) and SVR
(A) HCV monoinfected. (B) HCV/HIV co-infected.
Figure 2
Figure 2
Influence of estimated duration of infection on SVR among HCV monoinfected participants, by HCV genotype (n=171)
Figure 3
Figure 3
Influence of IFNL4 genotype on SVR among HCV monoinfected participants, by HCV genotype (n=164)
Figure 4
Figure 4. Kaplan-Meier survival graph of time to HCV virological clearance among all HCV-infected participants (n=432)
(A) Stratified by treatment. (B) Stratified by treatment and gender (treatment & gender interaction p=0.034).
See this image and copyright information in PMC

References

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