Elsevier

Journal of Hepatology

Volume 64, Issue 5, May 2016, Pages 1020-1026
Journal of Hepatology

Research Article
Hepatitis C reinfection after sustained virological response

https://doi.org/10.1016/j.jhep.2016.01.001Get rights and content

Background & Aims

On-going risk behaviour can lead to hepatitis C virus (HCV) reinfection following successful treatment. We aimed to assess the incidence of persistent HCV reinfection in a population of people who inject drugs (PWID) who had achieved sustained virological response (SVR) seven years earlier.

Methods

In 2004–2006 we conducted a multicentre treatment trial comprising HCV genotype 2 or 3 patients in Sweden, Norway and Denmark (NORTH-C). Six months of abstinence from injecting drug use (IDU) was required before treatment. All Norwegian patients who had obtained SVR (n = 161) were eligible for participation in this long-term follow-up study assessing virological and behavioural characteristics.

Results

Follow-up data were available in 138 of 161 (86%) individuals. Persistent reinfection was identified in 10 of 94 (11%) individuals with a history of IDU prior to treatment (incidence rate 1.7/100 person-years (PY); 95% CI 0.8–3.1) and in 10 of 37 (27%) individuals who had relapsed to IDU after treatment (incidence rate 4.9/100 PY; 95% CI 2.3–8.9). Although relapse to IDU perfectly predicted reinfection, no baseline factor was associated with reinfection. Relapse to IDU was associated with age <30 years (vs. ⩾40 years) at treatment (adjusted odds ratio [aOR] 7.03; 95% CI 1.78–27.8) and low education level (aOR 3.64; 95% CI 1.44–9.18).

Conclusions

Over time, persistent HCV reinfection was common among individuals who had relapsed to IDU after treatment. Reinfection should be systematically addressed and prevented when providing HCV care for PWID.

Introduction

Injecting drug use (IDU) is the main risk factor for hepatitis C virus (HCV) transmission in high-income countries, accounting for the majority of both new and existing cases [1]. Although HCV treatment among people who inject drugs (PWID) has shown good outcomes [2] and is recommended by international guidelines [3], [4], [5], access to treatment remains limited in this population due to multiple barriers to care [6], [7]. With increasing use of highly effective and tolerable direct-acting antivirals (DAAs), HCV treatment for PWID might become much more feasible in the near future. However, while a partial protective immunity may exist [8], on-going risk behaviour can lead to HCV reinfection following successful treatment.

In the first published study of HCV reinfection following sustained virological response (SVR) [9], we demonstrated low reinfection rates despite frequent relapse to drug use following a period of abstinence during treatment. Most succeeding studies [10], [11], [12], [13], [14], [15] have reported similarly low rates and a meta-analysis [2] reported an incidence of 2.4/100 person-years (PY) among individuals who had injected drugs ever and moderately higher (6.4/100 PY) among those with continued risk behaviour after treatment.

However, these studies have been limited either by small sample sizes, short longitudinal follow-up or lack of methods to distinguish between viral relapse and reinfection. Heterogeneity in study populations and in HCV testing intervals [16] may also have biased reinfection incidence estimates and accounted for the differences observed between studies. Furthermore, data concerning long-term reinfection outcomes, particularly clinically relevant persistent reinfections, are very limited. More data are therefore needed to resolve controversies and guide treatment decisions in a growing population of former and current PWID receiving HCV treatment.

The primary aim of this study was to assess the incidence of persistent HCV reinfection in a population of PWID who seven years earlier had achieved SVR following at least six months of abstinence from drug use prior to treatment in the NORTH-C trial. The secondary aims were to assess the proportion of PWID who had relapsed to IDU after treatment and to identify factors associated with reinfection and relapse to IDU.

Section snippets

Patient population

In 2004–2006, we performed a randomized controlled multicentre trial to assess the effect of short treatment with pegylated interferon alpha and ribavirin in a population dominated by PWID (NORTH-C) [17]. The NORTH-C trial comprised 428 mono-infected HCV genotype 2 or 3 patients in Norway, Sweden and Denmark of which 68% were infected through IDU. Patients on opioid substitution treatment (OST) were excluded. Patients with a rapid virological response (RVR) were randomized to 14 or 24 weeks

Patient characteristics

Of 161 Norwegian patients who had achieved SVR in the NORTH-C trial, 106 had acquired HCV infection through IDU while 55 had other routes of transmission. Nine patients had died during the follow-up period (Supplementary Table 2). Follow-up data were available in 138 of 161 (86%) eligible individuals, either collected by questionnaire (n = 105), telephone interview (n = 2) or chart review (n = 31).

Characteristics of included patients are shown in Table 1. The median age at treatment was 36 years (IQR

Discussion

This study assessed HCV reinfection seven years following SVR in a population mainly comprising PWID who had been abstinent from drug use at least six months prior to HCV treatment. Among 94 individuals with a history of IDU prior to treatment, 39% had relapsed to IDU after treatment. Persistent reinfection was observed in 11% of individuals with a history of IDU and in 27% of those who had relapsed to IDU after treatment. The incidence of persistent HCV reinfection was 1.7/100 PY among

Financial support

HM received research grants from the Norwegian ExtraFoundation for Health and Rehabilitation.

Conflict of interest

HM has held sponsored lectures for Roche, Medivir and Abbvie. OD is a consultant/advisor and has received research grants from Gilead Sciences, Merck, Abbvie and Medivir. LNK is a consultant/advisor for Gilead Sciences and Abbvie. PKS has held sponsored lectures for Roche and Schering-Plough. JOR is a consultant/advisor for Abbvie.

Authors’ contributions

HM developed the protocol, contributed to data collection, performed the statistical analyses and drafted the manuscript. BB developed the protocol, organized the data collection and revised the manuscript. AM, ZK, HK, JKD, JP, LH, PKS, JOR and LNK contributed to data collection and revised the manuscript. KSJ, JHOP and DHD performed the molecular characterisation and sequence analyses and revised the manuscript. OD developed the protocol, supervised the study and contributed to data

Acknowledgements

The remaining Norwegian NORTH-C group: J Almark, B Andersen, K Bjøro, K Bø, TF Engan, S Ertresvåg, J Florholmen, M Gangsøy-Kristiansen, TH Henriksen, O Hope, B Hiåsen, V Høeg, K Landrø, O Lange, J Langtind, I Melkeraaen, E Melsom, OS Moen, G Noraberg, E Reinertsen, I Slørdal, H Steinum, F Strøm, R Torp and K Wesenberg. M Holberg-Petersen, AB Kran and K Jakobsen at the Department of Microbiology, Oslo University Hospital. H Midgard received research grants from the Norwegian Extra Foundation for

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