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CROI 2015: Re-infection Due to Ongoing Risk Is Probably the Cause of HCV Recurrence After SVR

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

[Produced in collaboration with Aidsmap]

At one end of the spectrum, over a fifth of people with HIV/HCV coinfection who cleared HCV with treatment experienced a recurrence of infection. This compared to a rate of just 1% in patients with no HCV risk factors. The U.K. 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 response to treatment.

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 12 or 24 weeks after the completion of therapy -- in up to 90% of patients.    

But a minority of patients who have a successful response to therapy experience a subsequent recurrence of HCV infection. Many treated patients continue to have ongoing risk for 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, Andrew Hill from Chelsea and Westminster Hospital in London and colleagues did a meta-analysis of studies looking at rates of HCV recurrence among people who were successfully treated for HCV.

The patients were divided into 3 groups according to their HCV risk: low risk (HCV monoinfected patients with no risk factors for re-infection), high-risk (injection drug users and prisoners), and people with HIV/HCV coinfection.

Successful treatment was defined as SVR, typically 24 weeks after the completion of therapy. Recurrence was defined as detection of HCV RNA 6 or more months after SVR.

Results of 66 separate studies involving over 11,000 patients were analyzed by the investigators. Most individuals received treatment consisting of pegylated interferon and ribavirin before the advent of interferon-free direct-acting antiviral therapy.

There were 43 studies involving low-risk patients (n=9,419). 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 5-year recurrence rate of just over 1%.

There were 16 studies involving 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 HCV infection. The incidence rate was 2.8 per 100 person-years, and there was a 13% 5-year recurrence rate.

There were 7 studies involving HIV/HCV coinfected individuals (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 5-year recurrence rate was almost 22%. 5-year incidence among coinfected patients differed according to study design, and was a little over 1% for those enrolled in randomized controlled trials but 25% for those in cohort studies.

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

3/13/15

Reference

A Hill, B Simmons, J Saleen, and G Cook. Risk of Late Relapse or Re-infection with Hepatitis C after Sustained Virological Response: Meta-analysis of 66 Studies in 11,071 Patients. 2015 Conference on Retroviruses and Opportunistic Infections. Seattle, February 23-24, 2015. Abstract 654.