Re-infection due to ongoing risk probably the cause of HCV recurrence after SVR

Rates of hepatitis C virus (HCV) reoccurrence after successful therapy differ markedly between risk groups, according to the results of a meta-analysis presented at the recent Conference on Retroviruses and Opportunistic Infections (CROI 2015) in Seattle, USA.

At one end of the spectrum, over a fifth of people with HIV co-infection who cleared HCV infection with treatment experienced a recurrence of the infection. This compared to a rate just 1% in patients with no HCV risk factors. The UK investigators leading the study believe these large differences point to re-infection rather than relapse being the cause of the re-emergence of HCV after treatment response.

HCV infection is an increasingly important cause of liver-related illness and death around the world. Diagnosing and treating HCV is therefore a global health priority, especially as therapy with combinations of new direct-acting anti-HCV drugs can achieve a cure or sustained virological response (SVR) – absence of HCV RNA 24 weeks after the completion of therapy – in up to 90% of patients.    

Glossary

sustained virological response (SVR)

The continued, long-term suppression of a virus as a result of treatment. In hepatitis C, refers to undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 12 or 24 weeks after ending treatment and is considered to be a cure (SVR12 or SVR24).

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.

relapse

The return of signs and symptoms of a disease after a patient has been free of those signs and symptoms. 

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.

ribonucleic acid (RNA)

The chemical structure that carries genetic instructions for protein synthesis. Although DNA is the primary genetic material of cells, RNA is the genetic material for some viruses like HIV.

 

But a minority of patients who have a successful response to therapy experience a subsequent reoccurrence of HCV infection. Many treated patients continue to have an ongoing risk of HCV infection, so it is possible that recurrences are due to HCV re-infection rather than relapse after treatment.

To see if this is the case, researchers looked at rates of HCV recurrence among people who were successfully treated for HCV.

The patients were divided into three groups according to their HCV risk: low risk (mono-infected patients with no risk factors for re-infection); high-risk (people who inject drugs and people in prison settings); and people with HIV/HCV co-infection.

Successful treatment was defined as SVR 24 weeks after the completion of therapy. Recurrence was defined as detection of HCV RNA six or more months after SVR.

Results of 66 separate studies involving over 11,000 patients were analysed by the investigators. Most individuals received treatment consisting of pegylated interferon and ribavirin.

There were 43 studies involving low-risk patients (n = 9419). During a mean of 4.1 years of follow-up, 87 of these individuals experienced a recurrence of HCV. This provided a recurrence incidence of 0.23 per 100 person-years and a five-year recurrence rate of just over 1%.

Sixteen studies involved high-risk patients (n = 819). These individuals were followed for a mean of 2.9 years post-SVR and during this time 53 individuals had a recurrence of the infection. The incidence rate was 2.8 per 100 person-years, and there was a 13% five-year recurrence rate.

There were seven studies involving people with HIV and HCV co-infection (n = 833). There were 123 cases of HCV recurrence during a mean of 3.1 years of follow-up. Incidence was 4.78 per 100 person-years, and the five-year recurrence rate was almost 22%. Five-year incidence among people with co-infection differed according to study design, and was a little over 1% for those enrolled in randomised controlled trials but 25% for those in cohort studies.

Because of the large differences in outcomes between risk groups, the investigators conclude that most HCV recurrences after SVR are probably due to re-infection due to ongoing risk rather than relapse.

References

Hill A et al. Risk of late relapse or re-infection with hepatitis C after sustained virological response: meta-analysis of 66 studies in 11,071 patients. Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 654, 2015.