Risk of Late Relapse or Reinfection With Hepatitis C Virus After Achieving a Sustained Virological Response: A Systematic Review and Meta-analysis

Abstract

Background: Treatment for hepatitis C virus (HCV) can lead to sustained virological response (SVR) in over 90% of people. Subsequent recurrence of HCV, either from late relapse or reinfection, reverses the beneficial effects of SVR.

Methods: A search identified studies analysing HCV recurrence post-SVR. The recurrence rate for each study was calculated using events/person years of follow-up (PYFU). Results were pooled using a random-effects model and used to calculate 5-year recurrence risk. Three patient groups were analysed: (1) Mono-HCV infected "low-risk" patients; (2) Mono-HCV infected "high-risk" patients (injecting drug users or prisoners); (3) human immunodeficiency virus (HIV)/HCV coinfected patients. Recurrence was defined as confirmed HCV RNA detectability post-SVR.

Results: In the 43 studies of HCV mono-infected "low-risk" patients (n = 7969) the pooled recurrence rate was 1.85/1000 PYFU (95% confidence interval [CI], .71-3.35; I(2) = 73%) leading to a summary 5-year recurrence risk of 0.95% (95% CI, .35%-1.69%). For the 14 studies of HCV monoinfected "high-risk" patients (n = 771) the pooled recurrence rate was 22.32/1000 PYFU (95% CI, 13.07-33.46; I(2) = 27%) leading to a summary 5-year risk of 10.67% (95% CI, 6.38%-15.66%). For the 4 studies of HIV/HCV coinfected patients the pooled recurrence rate was 32.02/1000 PYFU (95% CI, .00-123.49; I(2) = 96%) leading to a summary 5-year risk of 15.02% (95% CI, .00%-48.26%). The higher pooled estimates of recurrence in the high-risk and coinfected cohorts were driven by an increase in reinfection rather than late relapse.

Conclusions: SVR appears durable in the majority of patients at 5 years post-treatment. The large difference in 5 year event rate by risk group is driven mainly by an increased reinfection risk.

Keywords: hepatitis C; recurrence; reinfection; relapse; sustained virologic response.

Figure 1.

Flow diagram of study selection for systematic review of hepatitis C virus (HCV) recurrence in patients achieving a sustained virologic response after treatment for HCV infection. Low-risk studies include those examining recurrence in general populations and high-risk studies include those studying patients with at least 1 reinfection risk factor (injecting drug use or prison populations). Human immunodeficiency virus (HIV)/HCV coinfected studies include all those of coinfected participants, regardless of risk factors. Total studies in the 3 groups does not equal the total number of studies identified as 2 studies examined 2 populations.

Figure 2.

Summary 5-year risk (95% confidence interval) of recurrence post-sustained virological response (SVR), by risk group. Presented are the pooled estimates for the 5-year risk of recurrence after achieving an SVR. Also shown are the number of studies that were included to derive each estimate. Abbreviations: HCV, hepatitis C virus; HIV, human immunodeficiency virus.