Incidence, risk factors, and prevention of hepatitis C reinfection: a population-based cohort study.
Islam N et al
Lancet Gastroenterol 2017 ; 2 (3) March :200-210.

Background: People remain at risk of reinfection with hepatitis C virus (HCV), even after clearance of the primary infection. We identified factors associated with HCV reinfection risk in a large population-based cohort study in British Columbia, Canada, and examined the association of opioid substitution therapy and mental health counselling with reinfection.

Methods: We obtained data from the British Columbia Hepatitis Testers Cohort, which includes all individuals tested for HCV or HIV at the British Columbia Centre for Disease Control Public Health Laboratory during 1990–2013 (when data were available). We defined cases of HCV reinfection as individuals with a positive HCV PCR test after either spontaneous clearance (two consecutive negative HCV PCR tests spaced ≥28 days apart without treatment) or a sustained virological response (SVR; two consecutive negative HCV PCR tests spaced ≥28 days apart 12 weeks after completing interferon-based treatment). We calculated incidence rates of HCV reinfection (per 100 person-years of follow-up) and corresponding 95% CIs assuming a Poisson distribution, and used a multivariable Cox proportional hazards model to examine reinfection risk factors (age, birth cohort, sex, year of HCV diagnosis, HCV clearance type, HIV co-infection, number of mental health counselling visits, levels of material and social deprivation, and alcohol and injection drug use), and the association of opioid substitution therapy and mental health counselling with HCV reinfection among people who inject drugs (PWID).

Findings: 5915 individuals with HCV were included in this study after clearance (3690 after spontaneous clearance and 2225 after SVR). 452 (8%) patients developed reinfection; 402 (11%) after spontaneous clearance and 50 (2%) who had achieved SVR. Individuals were followed up for a median of 5·4 years (IQR 2·9–8·7), and the median time to reinfection was 3·0 years (1·5–5·4). The overall incidence rate of reinfection was 1·27 (95% CI 1·15–1·39) per 100 person-years of follow-up over a total of 35 672 person-years, with significantly higher rates in the spontaneous clearance group (1·59, 1·44–1·76) than in the SVR group (0·48, 0·36–0·63). With the adjusted Cox proportional hazards model, we noted higher reinfection risks in the spontaneous clearance group (adjusted hazard ratio [HR] 2·71, 95% CI 2·00–3·68), individuals co-infected with HIV (2·25, 1·78–2·85), and PWID (1·53, 1·21–1·92) than with other reinfection risk factors. Among the 1604 PWID with a current history of injection drug use, opioid substitution therapy was significantly associated with a lower risk of reinfection (adjusted HR 0·73, 95% CI 0·54–0·98), as was engagement with mental health counselling services (0·71, 0·54–0·92).

Interpretation: The incidence of HCV reinfection was higher among HIV co-infected individuals, those who spontaneously cleared HCV infection, and PWID. HCV treatment complemented with opioid substitution therapy and mental health counselling could reduce HCV reinfection risk among PWID. These findings support policies of post-clearance follow-up of PWID, and provision of harm-reduction services to minimise HCV reinfection and transmission.

Expert's Commentary

« This is to date the largest population-based study on HCV reinfection and calls for continued awareness among health care providers even years after reaching HCV cure. In the presented study, HCV reinfection was in particular associated with injecting drug use and HIV coinfection. These subgroups represent individuals with a specific risk behavior pattern, but especially PWID have historically been underrepresented in HCV treatment cohorts from the interferon era. With much easier HCV treatment options available HCV therapy will be expanded to much more challenging patient populations with ongoing drug use and high risk of HCV reinfection. Indeed, considerable reinfection rates in all oral DAA trials have been reported recently in persons receiving opioid agonist therapy with high rates of ongoing drug use (1). Therefore, the risk of reinfection needs to part of a treatment approach and behavior counselling in every therapy setting with high-risk individuals. Being on opiate substitution treatment (OST) or to receive mental health counselling in this analysis reduced the likelihood for an HCV reinfection. Therefore, these findings underline that there needs to be a continued effort for supporting harm reduction programs which more recently have been financially challenged. »

Pr Jürgen Rockstroh, University of Bonn

1. Dore GJ, et al. C-EDGE CO-STAR Study Group. Elbasvir-Grazoprevir to Treat Hepatitis C Virus Infection in Persons Receiving Opioid Agonist Therapy: A Randomized Trial.
   Ann Intern Med. 2016 Nov 1;165(9):625-634