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Five–Year Risk of Late Relapse or Reinfection With Hepatitis C After Sustained Virological Response: Meta-analysis of 49 Studies in 8534 Patients
Andrew M. Hill1, Bryony Simmons2, Jawaad Saleem2, Graham Cooke2
1 St Stephens AIDS Trust, Chelsea and Westminster Hospital, London, United Kingdom. 2 Global Health, St Mary's Hospital–Imperial College Healthcare NHS Trust, London, United Kingdom.
Background: Combination treatment with direct acting antivirals can lead to sustained virological response (SVR) in over 90% of people with Hepatitis C (HCV) infection. However, subsequent recurrence of HCV (either from late relapse or re-infection) reverses the beneficial effects of SVR. This analysis aimed to estimate the 5-year risk of HCV late relapse or re-infection post-SVR, by risk group.
Methods: The MEDLINE and EMBASE databases were searched for studies analysing late relapse or re-infection post-SVR (typically 24 weeks post-treatment, using pegylated interferon/ribavirin). All studies with >6 months of follow up post-SVR were included. Three groups of patients were analysed: 1. Mono-HCV infected “low risk” patients; 2. Mono-HCV infected “high risk” patients (IV drug users or prisoners); 3. HIV/HCV co-infected patients. Studies of liver transplant patients were excluded. Recurrence was defined as confirmed HCV RNA detectability after SVR (at least 6 months after end of treatment).
Results: Results were available from 49 studies in 8534 patients. In each risk group, there were progressive rises in the risk of HCV recurrence with longer follow up time. In the 24 studies of HCV mono-infected “low risk” patients (n=6046) there were 45 HCV recurrences during a mean 4.1 years of follow up (estimated 5 year rate=0.9%). For the 15 studies of HCV mono-infected “high risk” patients (n=1203) there were 102 HCV recurrences during a mean 5.0 years of follow up (estimated 5-year rate=8.1%). For the 10 studies of HIV/HCV co-infected patients (n=1285) there were 178 HCV recurrences during a mean 3.3 year follow up (estimated 5-year rate=21.8%). For the studies of HIV/HCV co-infected patients, 5-year rates of HCV recurrence were significantly lower for patients followed up after randomised clinical trials (1.25%), compared to unselected patient cohorts (24.0%) (p<0.001).
Conclusions: In this analysis of 49 studies, the 5-year risk of late relapse or re-infection post-SVR was 0.9% in HCV mono-infected “low risk” patients, 8.1% in HCV mono-infected IV drug users or prisoners, and 21.8% in HIV/HCV co-infected patients. The large differences in event rates by risk group suggest that re-infection is more significantly more common than late relapse. Studies which follow up HIV/HCV co-infected patients originally enrolled in clinical trials may underestimate the risk of HCV re-infection in the general population
|Risk Group||Mono-infection, low-risk||Mono-infection high risk||HIV/HCV co-infected|
|Number of patients||6046||1203||1285|
|Mean Follow up (years)||4.1||5.0||3.3|
|5-year re-infection risk (%)||0.9%||8.1%||21.8%|