Long‐term assessment of recurrence of hepatocellular carcinoma in patients with chronic hepatitis C after viral cure by direct‐acting antivirals

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background and Aim</jats:title><jats:p>Early hepatocellular carcinoma (HCC) recurrence is common, even after achieving hepatitis C virus (HCV) cure. This study was carried out to assess the long‐term trends and predictors of recurrence after HCV cure by direct‐acting antivirals (DAAs).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This retrospective, multicenter cohort study enrolled 365 consecutive patients with chronic hepatitis C who required HCC treatment following sustained viral response (SVR) by DAA administration. Patients with HCC recurrence before SVR were excluded. Late HCC recurrence and its predictors beyond the post‐treatment early phase (24 weeks after SVR) were evaluated.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The data of 326 patients were available for the final analysis. The median follow‐up duration from SVR determination was 2.7 years. Median age was 74, and 220 (67.5%) were 70 or over. The corresponding 5‐year cumulative HCC recurrence rates of previous curative and palliative treatment groups were 45.4% and 65.7%, respectively (log‐rank test: <jats:italic>P</jats:italic> < 0.001). Cox regression multivariable analysis revealed that cirrhosis (hazard ratio [HR] 1.85, <jats:italic>P</jats:italic> = 0.021), the number of HCC nodules (≥ 2) (HR 1.52, <jats:italic>P</jats:italic> = 0.031), and previous palliative HCC treatment (HR 1.71, <jats:italic>P</jats:italic> = 0.012) were independent predictors of late recurrence, in addition to the predictors of early recurrence; AFP > 7 ng/mL at 12 weeks after DAA administration, time from HCC complete response (CR) to DAA initiation (< 1 year), and the number of HCC treatments necessary to achieve CR (≥ 2).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The evaluation of fibrosis and characteristics of the previous HCC would allow for better HCC recurrence stratification, which would be helpful for developing long‐term surveillance strategies.</jats:p></jats:sec>