Association Between Viral Replication Activity and Postoperative Recurrence of HBV-Related Hepatocellular Carcinoma

Baseline viral replication activity influences the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B virus (HBV) infection.

To evaluate the impact of baseline viral replication activity on recurrence in HBV-related HCC after curative resection.

A multinational retrospective cohort of 2384 patients with very early or early-stage HBV-related HCC who consecutively underwent curative resection and received antiviral therapy (AVT) between 2010 and 2018 was analysed. Patients were categorised into ongoing-AVT (previously on AVT with viral suppression) and initiation-AVT (initiated AVT at the time of resection) groups. HCC recurrence was compared between these two groups based on baseline viral replication activity.

During a median follow-up of 4.9 years, 1188 (49.8%) patients developed recurrence. Multivariable analysis showed similar recurrence risk between the ongoing-AVT and initiation-AVT groups (HR, 1.09; 95% CI, 0.96-1.24). However, in cirrhotic patients, the initiation-AVT group had a higher recurrence risk than the ongoing-AVT group (HR, 1.22; 95% CI, 1.02-1.45) but not in non-cirrhotic patients (HR, 0.90; 95% CI, 0.73-1.09). Intriguingly, in the non-cirrhotic initiation-AVT group, a parabolic association was observed between baseline HBV DNA levels and the risk of recurrence, with those having 5-6 log₁₀ IU/mL HBV DNA levels showing significantly higher recurrence risk compared to the ongoing-AVT group (HR, 1.78; 95% CI, 1.32-2.42).

The association between HBV replication activity and the risk of HCC recurrence varied depending on cirrhosis, providing important insights for optimising the timing of AVT and post-operative surveillance strategies.