Smoking as a Risk Factor for Very Late Recurrence in Surgically Resected Early-Stage Primary Hepatocellular Carcinoma

Background: The risk of first recurrence of hepatocellular carcinoma (HCC) within years 5 to 10 after curative hepatectomy remains unknown. We aimed to assess the incidence and prognostic factors for very late recurrence among patients who achieved 5 years' recurrence-free survival (RFS) after primary resection.Methods: We retrospectively analyzed 337 patients with early-stage HCC underwent primary tumor resection and achieved more than 5 years' RFS.Results: A total of 77 patients (22.8%) developed very late recurrence. The cumulative very late recurrence rate increased from 6.9% and 11.7% to 16.6% at 6, 7, and 8 years, respectively. Patients stopped smoking had a higher rate of very late RFS.Conclusions: The high rates of very late recurrence in HCC indicate that patients warrant continued surveillance, even after 5 recurrence-free years. Moreover, smoking is a risk factor for very late HCC recurrence, and quitting smoking may reduce the risk of very late recurrence.