Systematic review with meta‐analysis: recurrence of hepatocellular carcinoma following direct‐acting antiviral therapy

Summary Background Although studies suggest decreased incident hepatocellular carcinoma (HCC) after direct‐acting antivirals (DAA), data are conflicting regarding HCC recurrence and aggressiveness in patients who have a history of HCC with complete response. Aim Characterize HCC recurrence patterns after DAA therapy. Methods Two reviewers searched MEDLINE and SCOPUS from January 2015 to December 2017 and identified studies evaluating HCC recurrence patterns following DAA therapy. A pooled estimate was calculated using the DerSimonian and Laird method for a random effects model. The study was conducted in accordance with PRISMA guidelines. Results Among 24 studies (n = 1820 patients), the proportion of patients with HCC recurrence following DAA therapy ranged from 0% to 59% (pooled estimate 24.4%; 95% CI: 18.4%‐30.4%). Among 11 full text manuscripts, pooled HCC recurrence was 21.9% (95% CI: 16.2%‐28.3%). Factors associated with recurrence included history of prior HCC recurrence and a shorter interval between HCC complete response and DAA initiation. Nine studies comparing DAA‐treated and interferon‐treated or untreated patients found similar recurrence among DAA‐treated patients. Most (77.8%) patients with HCC recurrence were detected at an early tumour stage, of whom 64.7% received curative treatment. Study limitations included heterogeneous cohorts, potential misclassification of HCC absence prior to DAA, ascertainment bias for recurrence, and short durations of follow‐up. Conclusions Current data suggest acceptable HCC recurrence rates after DAA therapy, particularly if DAA therapy is delayed at least 6 months after HCC complete response. However, data characterising HCC recurrence after DAA therapy are of limited quality, highlighting the need for high quality prospective studies.