HBsAg seroclearance in chronic hepatitis B: implications for hepatocellular carcinoma

The long-term clinical course, including the development of hepatocellular carcinoma (HCC) after hepatic B surface antigen (HBsAg) seroclearance is not established. We discovered that the incidence of HCC and the risk factors for HCC in chronic hepatitis B (CHB) patients after HBsAg seroclearance.

During 28 years, 96 CHB patients with HBsAg seroclearance were retrospectively reviewed. These patients continued to undergo HCC surveillance. The median follow-up time from initial visit was 166.5 months (range, 7 to 321 mo).

The mean age at the initial visit and at the time of seroclearance was 39.2 ± 10.6 years and 46.4 ± 9.9 years, respectively. The mean age at the time of HBsAg seroclearance was significantly lower (P=0.03) in patients with spontaneous HBsAg seroclearance than patients with treatment-associated HBsAg seroclearance. During a median of 56 months (range, 7 to 238 mo) of follow-up after HBsAg seroclearance, 6 (6.5%) patients developed HCC. The mean age at the time of developing HCC was 55.8 ± 10.3 years. On univariate analysis, the evidence of liver cirrhosis from the time of HBsAg seroclearance and age more than 45 years at the time of HBsAg seroclearance were significant risk factors for HCC development. In multivariate analysis, the evidence of liver cirrhosis at HBsAg seroclearance was the only significant risk factor for HCC development.

HCC can develop after HBsAg seroclearance in patients with known cirrhosis. Patients who achieved HBsAg seroclearance at older age (>45) may have undiagnosed cirrhosis and hence remain at risk for HCC. HCC surveillance should be carried out for both of those patient populations.