Reinfection after hepatitis C cure: prevention may require long-term support for people who have injected drugs

Reinfection rates after hepatitis C cure among people who inject drugs, as well as past drug users, are relatively low, according to findings from studies from Norway and Canada presented at the International Liver Congress in Vienna, Austria, in April.

The findings suggest that current and former injecting drug users who have been cured of hepatitis C require ongoing support to remain free of hepatitis C, but also indicate that fears of a high rate of reinfection should not be used as a reason to withhold hepatitis C treatment from people who inject drugs.

A meta-analysis of studies of hepatitis C treatment outcomes in people who inject drugs, published in 2013, found an incidence of between 2.4 and 6.4 per 100 person-years of follow-up, but a subsequent meta-analysis found that the reinfection rate could be as high as 8%. (Aspinall 2013, Hill 2014)

Further data presented at the International Liver Congress found rates of 3.6 per 100 person-years and 4.6 per 100 person-years among similarly sized cohorts in Montreal and Norway respectively.

In the Norwegian study, investigators found that people who inject drugs were at high risk of reinfection during a 7-year follow-up period, in large part due to the frequent resumption of injecting drug use after a hepatitis C cure.

In contrast, a study among people with a high risk of reinfection carried out in Montreal, Canada, found a somewhat lower incidence of reinfection among people cured of hepatitis C, but the study also noted a significant association between reinfection and resumption of injecting drug use – often after long periods off drugs.

The Norwegian study investigated the frequency of reinfection in a national cohort of people treated for hepatitis C with pegylated interferon and ribavirin in the NORTH-C trial in 2004, who had achieved a cure (SVR24). In total, 161 people were cured, of whom 138 were available for follow up, the remainder having either died or become lost to follow-up. Of these, 94 had been injecting drug users prior to treatment, while the remaining 44 were not. After a median of seven years post-treatment, 37% of those who had injected drugs prior to hepatitis C treatment had resumed injecting drugs, and of these, 49% were injecting drugs frequently (reporting a minimum of 100 injections). Thirteen per cent of all people who had resumed injecting drug use had become reinfected with hepatitis C (a total of 12 infections). The rate of reinfection was 1.2 per 100 person years of follow up, 1.8 per 100 person years among people who had ever injected drugs, and 4.7 per 100 person years among those who resumed injecting drug use after achieving a cure.

Lower educational level (secondary school education) and age below 40 were identified as risk factors for reinfection in multivariate analysis.

The Montreal study looked at 338 people cured of hepatitis C at a single clinic in Montreal up to the end of 2013 (the HEPVIRAC cohort). Montreal has a high incidence of HCV infection among people who inject drugs (26 per 100 person-years), and researchers wanted to find out whether the reinfection rate was higher among people who inject drugs, and whether particular risk factors for reinfection could be identified in this population. Participants in the cohort study were tested once year for HCV RNA after being cured, and the date of reinfection was estimated as the midpoint between the last negative test and the first positive test.

Of the 338 cured patients, 82% had been exposed to HCV through injecting drug use. Twenty-two members of the cohort became reinfected with HCV after being cured during a median of 2.7 person-years of follow-up, an overall reinfection rate of 1.7 per 100 person-years of follow up. The reinfection rate among active injecting drug users was 3.6 per 100 person-years.

The study found a median time to reinfection of 14.7 years, suggesting that long-term support for safer injecting practices will be needed for people cured of hepatitis C, as well as support for sustained recovery from drug use for people who stop using drugs, in order to maximise the avoidance of hepatitis C reinfection. Fifteen of 22 reinfections took place in people considered by researchers to have been “in remission” from active injecting drug use, and remission was significantly associated with reinfection when compared to active drug use (p = 0.044). The proportion of previous drug users who resumed injecting drug use during the follow-up period was not reported.

Two other factors were significantly associated with reinfection: lack of stable housing (p = 0.039), and HIV/HCV co-infection (p = 0.010). Male gender and active injecting drug use showed a trend towards association, but trends failed to reach statistical significance (p = 0.052, 0.056 respectively).

Neither study reported on opioid substitution therapy usage, or on uptake of harm reduction measures among cohort participants, both of which might be expected to have an influence on injecting behaviours and the subsequent risk of reinfection. Future studies in well-characterised cohorts could provide valuable operational evidence by looking at these factors.