Risk of late relapse or reinfection with Hepatitis C virus after achieving a sustained virological response: A systematic review and meta-analysis
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Accepted version
Published version
Author(s)
Simmons, B
Saleem, J
Hill, A
Riley, R
Cooke, GS
Type
Journal Article
Abstract
Background. Treatment for hepatitis C virus (HCV) can lead to sustained virological response (SVR) in over 90% of people. Subsequent recurrence of HCV, either from late relapse or reinfection, reverses the beneficial effects of SVR.
Methods. A search identified studies analysing HCV recurrence post-SVR. The recurrence rate for each study was calculated using events/person years of follow-up (PYFU). Results were pooled using a random-effects model and used to calculate 5-year recurrence risk. Three patient groups were analysed: (1) Mono-HCV infected “low-risk” patients; (2) Mono-HCV infected “high-risk” patients (injecting drug users or prisoners); (3) human immunodeficiency virus (HIV)/HCV coinfected patients. Recurrence was defined as confirmed HCV RNA detectability post-SVR.
Results. In the 43 studies of HCV mono-infected “low-risk” patients (n = 7969) the pooled recurrence rate was 1.85/1000 PYFU (95% confidence interval [CI], .71–3.35; I2 = 73%) leading to a summary 5-year recurrence risk of 0.95% (95% CI, .35%–1.69%). For the 14 studies of HCV monoinfected “high-risk” patients (n = 771) the pooled recurrence rate was 22.32/1000 PYFU (95% CI, 13.07–33.46; I2 = 27%) leading to a summary 5-year risk of 10.67% (95% CI, 6.38%–15.66%). For the 4 studies of HIV/HCV coinfected patients the pooled recurrence rate was 32.02/1000 PYFU (95% CI, .00–123.49; I2 = 96%) leading to a summary 5-year risk of 15.02% (95% CI, .00%–48.26%). The higher pooled estimates of recurrence in the high-risk and coinfected cohorts were driven by an increase in reinfection rather than late relapse.
Conclusions. SVR appears durable in the majority of patients at 5 years post-treatment. The large difference in 5 year event rate by risk group is driven mainly by an increased reinfection risk.
Methods. A search identified studies analysing HCV recurrence post-SVR. The recurrence rate for each study was calculated using events/person years of follow-up (PYFU). Results were pooled using a random-effects model and used to calculate 5-year recurrence risk. Three patient groups were analysed: (1) Mono-HCV infected “low-risk” patients; (2) Mono-HCV infected “high-risk” patients (injecting drug users or prisoners); (3) human immunodeficiency virus (HIV)/HCV coinfected patients. Recurrence was defined as confirmed HCV RNA detectability post-SVR.
Results. In the 43 studies of HCV mono-infected “low-risk” patients (n = 7969) the pooled recurrence rate was 1.85/1000 PYFU (95% confidence interval [CI], .71–3.35; I2 = 73%) leading to a summary 5-year recurrence risk of 0.95% (95% CI, .35%–1.69%). For the 14 studies of HCV monoinfected “high-risk” patients (n = 771) the pooled recurrence rate was 22.32/1000 PYFU (95% CI, 13.07–33.46; I2 = 27%) leading to a summary 5-year risk of 10.67% (95% CI, 6.38%–15.66%). For the 4 studies of HIV/HCV coinfected patients the pooled recurrence rate was 32.02/1000 PYFU (95% CI, .00–123.49; I2 = 96%) leading to a summary 5-year risk of 15.02% (95% CI, .00%–48.26%). The higher pooled estimates of recurrence in the high-risk and coinfected cohorts were driven by an increase in reinfection rather than late relapse.
Conclusions. SVR appears durable in the majority of patients at 5 years post-treatment. The large difference in 5 year event rate by risk group is driven mainly by an increased reinfection risk.
Date Issued
2016-03-15
Date Acceptance
2015-10-30
Citation
Clinical Infectious Diseases, 2016, 62 (6), pp.683-694
ISSN
1537-6591
Publisher
Oxford University Press (OUP)
Start Page
683
End Page
694
Journal / Book Title
Clinical Infectious Diseases
Volume
62
Issue
6
Copyright Statement
© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society
of America. This is an Open Access article distributed under the terms of the Creative Commons
Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/
4.0/), which permits non-commercial reproduction and distribution of the work, in any
medium, provided the original work is not altered or transformed in any way, and that the
work is properly cited. For commercial re-use, contact journals.permissions@oup.com.
of America. This is an Open Access article distributed under the terms of the Creative Commons
Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/
4.0/), which permits non-commercial reproduction and distribution of the work, in any
medium, provided the original work is not altered or transformed in any way, and that the
work is properly cited. For commercial re-use, contact journals.permissions@oup.com.
Sponsor
Medical Research Council (MRC)
Identifier
https://academic.oup.com/cid/article/62/6/683/2462988
Grant Number
MR/K01532X/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Infectious Diseases
Microbiology
hepatitis C
sustained virologic response
recurrence
relapse
reinfection
TERM-FOLLOW-UP
ANTIVIRAL THERAPY
PEGINTERFERON ALPHA-2A
INTERFERON MONOTHERAPY
GLOBAL EPIDEMIOLOGY
PLUS RIBAVIRIN
DURABILITY
INFECTION
OUTCOMES
COMBINATION
hepatitis C
recurrence
reinfection
relapse
sustained virologic response
Adolescent
Adult
Antiviral Agents
Coinfection
Drug Users
Female
Follow-Up Studies
HIV Infections
Hepacivirus
Hepatitis C
Hepatitis C, Chronic
Humans
Male
RNA, Viral
Recurrence
Ribavirin
Risk Factors
Sustained Virologic Response
Viral Load
Young Adult
Humans
Hepacivirus
Hepatitis C
Hepatitis C, Chronic
HIV Infections
Recurrence
RNA, Viral
Ribavirin
Antiviral Agents
Viral Load
Risk Factors
Follow-Up Studies
Adolescent
Adult
Female
Male
Drug Users
Young Adult
Coinfection
Sustained Virologic Response
Microbiology
06 Biological Sciences
11 Medical and Health Sciences
Publication Status
Published
Date Publish Online
2016-01-19