Attenuation of the second peak of bimodal recurrence of HBV-related HCC after curative treatment in the antiviral era.

[BACKGROUND & AIMS] Recurrence in patients with hepatocellular carcinoma (HCC) treated with curative surgery or ablation follows a bimodal pattern, with early recurrence peaking at 6 months to 1 year, and late recurrence peaking at 3 to 4 years. We postulate that the use of antiviral therapy may reduce late recurrence by improving control of chronic inflammation.

[METHODS] Patients with positive HBsAg and HCC (HBV-related HCC) who received curative surgery or ablation from October 2000 to July 2017 were recruited from Prince of Wales Hospital in Hong Kong. The primary endpoint was recurrence-free survival (RFS). We conducted time-dependent survival analysis and 6-month and 12-month landmark analyses to evaluate the impact of antiviral therapy on overall recurrence and late recurrence, respectively. We also conducted a secular trend analysis by stratifying patients into an early cohort (2001-2005) and a late cohort (2011-2015), representing periods of low and high antiviral usage, respectively, to assess changes in recurrence hazard over time.

[RESULTS] A total of 765 patients with HBV-related HCC were recruited. Median RFS was 31.1 (95% CI 26.6-39.4) months for the entire cohort. In the time-dependent survival analysis, antiviral therapy was associated with improved RFS in the univariate model (hazard ratio [HR] 0.84, 95% CI 0.74-0.99, p = 0.042), with a similar trend observed in the multivariable model (HR 0.86, 95% CI 0.72-1.03, p = 0.106). Baseline antiviral therapy significantly improved RFS in both the 6-month (HR 0.75, 95% CI 0.59-0.96, p = 0.019) and 12-month (HR 0.62, 95% CI 0.47-0.82, p = 0.001) multivariable landmark analyses. Secular trend analysis revealed attenuation of the second recurrence peak in the cohort with higher antiviral exposure.

[CONCLUSION] Among patients with HBV-related HCC who underwent curative surgery or ablation, antiviral therapy was associated with a reduction in late recurrence.

[IMPACT AND IMPLICATIONS] The classical bimodal recurrence pattern of hepatocellular carcinoma following curative treatment was established prior to the widespread use of effective antiviral therapy. It is unclear whether this recurrence pattern is still valid in the era of effective antiviral therapy. The current study shows that antiviral therapy can reduce late recurrence, resulting in loss of the second peak of the classical bimodal recurrence pattern. This study provides further evidence highlighting the importance of adherence to antiviral therapy in patients who received curative treatment for hepatocellular carcinoma.