Risk of Hepatocellular Carcinoma Decreases After Antiviral Therapy–Induced HBsAg Seroclearance

ABSTRACT Background Antiviral therapy (AVT) reduces the risk of hepatitis B virus–related hepatocellular carcinoma (HCC). Aims The difference in risk of HCC after hepatitis B surface antigen (HBsAg) seroclearance to the AVT status was explored. Methods Patients with chronic hepatitis B who achieved HBsAg seroclearance were retrospectively evaluated. The primary outcome was the development of HCC after HBsAg seroclearance. Results Of the study population, 1280 (84.2%) and 241 (15.8%) patients achieved HBsAg seroclearance without (spontaneous clearance group) and with AVT (AVT‐induced clearance group), respectively. HCC cumulative incidence was comparable between the two groups (hazard ratio [HR] = 0.461; log‐rank test, p = 0.197), whereas it was significantly lower in the AVT‐induced HBsAg clearance group than in the spontaneous HBsAg clearance group in inverse probability of treatment weighting analysis (HR = 0.442; log‐rank test, p = 0.004). In multivariate analysis, spontaneous HBsAg clearance, albumin–bilirubin (ALBI) grade ≥ 2, cirrhosis, and platelet count < 50 × 10 9 /L were independently associated with the increased risk of HCC. The newly established antiviral therapy, cirrhosis, ALBI, and platelet count (ACAP) scores had a C‐index of 0.765, and the time‐dependent areas under the curve of HCC prediction at 5 and 8 years were 0774 and 0.823, respectively. Conclusion The risk of HCC differed according to the AVT status after HBsAg seroclearance.