The risk of hepatitis C virus recurrence in hepatitis C virus-infected patients treated with direct-acting antivirals after achieving a sustained virological response: A comprehensive analysis

Background & Aims The risk for hepatitis C virus (HCV) recurrence persists after HCV eradication with direct-acting antivirals (DAAs), particularly in patients with ongoing high-risk behaviours. Our aim was to assess the risk of HCV recurrence (late relapse and/or reinfection) post-sustained virological response (SVR). Methods We searched the literature for studies reporting HCV recurrence rates post-SVR in PubMed, Web of Science and the Cochrane Library. Identified publications were divided into groups based on patient risk for HCV reinfection: low-risk HCV mono-infection, high-risk HCV mono-infection and a human immunodeficiency virus (HIV)/HCV coinfection. The HCV recurrence rate for each study was calculated by using events divided by the person-years of follow-up (PYFU). HCV recurrence was defined as confirmed, detectable HCV RNA post-SVR. Results In the 16 studies of low-risk patients, the pooled recurrence rate was 0.89/1000 PYFU (95% confidence interval [CI], 0.16-2.03). For the 19 studies of high-risk patients, the pooled recurrence rate was 29.37/1000 PYFU (95% CI, 15.54-46.91). For the eight studies of HIV/HCV-coinfected patients, the pooled recurrence rate was 23.25/1000 PYFU (95% CI, 4.24-53.39). The higher pooled estimates of recurrence in the high-risk and HIV/HCV-coinfected populations were predominantly driven by an increase in reinfection rather than late relapse. Conclusions The HCV recurrence risk after achieving SVR with all-oral DAAs therapy is low, and the risk of HCV recurrence in high-risk and HIV/HCV-coinfected populations was driven by an increase in reinfection rather than late relapse.