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)

Glossary

reinfection

In HIV, synonym for superinfection. In hepatitis C, used when someone who has been cured of the virus is infected with hepatitis C again.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

cure

To eliminate a disease or a condition in an individual, or to fully restore health. A cure for HIV infection is one of the ultimate long-term goals of research today. It refers to a strategy or strategies that would eliminate HIV from a person’s body, or permanently control the virus and render it unable to cause disease. A ‘sterilising’ cure would completely eliminate the virus. A ‘functional’ cure would suppress HIV viral load, keeping it below the level of detection without the use of ART. The virus would not be eliminated from the body but would be effectively controlled and prevented from causing any illness. 

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

remission

The disappearance of signs and symptoms of a disease, usually in response to treatment. The term is often used in relation to cancer, indicating that there is no evidence of disease, although the possibility of cancer remaining in the body cannot be ruled out. In HIV, remission is an alternative term for ‘functional cure’. A sustained ART-free remission would boost the immune system to induce long-term control of HIV, allowing a person living with HIV to maintain an undetectable viral load without daily medication.

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.

References

Aspinall EJ et al. Treatment of hepatitis C virus infection among people who are actively injecting drugs: a systematic review and meta-analysis. Clin Infect Dis 57(suppl 2):S80-S89, 2013.

Hill A et al. Effects of sustained virological response (SVR) on the risk of liver transplant, hepatocellular carcinoma, death and re-infection: meta-analysis of 129 studies in 23,309 patients with Hepatitis C infection. 2014 Annual Meeting of the American Association for the Study of Liver Diseases, Boston, abstract 44.

Machouf N et al. Sustainability of HCV cure in a population with a high risk of reinfection: Montreal’s experience. J Hepatology 62 (50th International Liver Congress), S15, P1250, 2015.

Midgard H, Bjøro B, Dalgard O. Incidence of hepatitis C reinfection following sustained virologic response—a seven year follow-up of Scandinavian patients infected through injecting drug use. Program and abstracts of the 50th Annual Meeting of the European Association for the Study of the Liver, Vienna, abstract O061.