Impact of age and gender on risk of hepatocellular carcinoma after hepatitis B surface antigen seroclearance

Background and Aims Previous studies suggested spontaneous seroclearance of hepatitis B surface antigen (HBsAg) was still associated with an increased risk of hepatocellular carcinoma (HCC), in patients ⩾50years of age. This study aimed to evaluate the risk of HCC after HBsAg seroclearance and the impact of gender on HCC. Methods All chronic hepatitis B patients under medical care in Hospital Authority, Hong Kong who had cleared HBsAg between January 2000 and August 2016 were identified. The age of the patient at HBsAg seroclearance, gender, and subsequent development of HCC were analyzed. Results A total of 4,568 patients with HBsAg seroclearance were identified; 793 (17.4%) were treated by nucleos(t)ide analogues and 60 (1.3%) had received interferon treatment. At a median (interquartile range) follow-up of 3.4 (1.5–5.0)years, 54 patients developed HCC; cumulative incidences of HCC at 1, 3 and 5years were 0.9%, 1.3% and 1.5%, respectively. Age above 50years (adjusted hazard ratio 4.31, 95% confidence interval 1.72–10.84; p =0.002) and male gender (2.47, 1.24–4.91; p =0.01) were two independent risk factors of HCC. Female patients aged ⩽50years (n=545) had zero risk of HCC within 5years of follow-up. Male patients aged ⩽50years (n=769), female patients aged >50years (n=1,149) and male patients aged >50years (n=2,105) had a 5-year cumulative incidence of HCC 0.7%, 1.0% and 2.5%, respectively. Similar findings were observed in patients with spontaneous and antiviral treatment-induced HBsAg seroclearance. Conclusions Female patients aged 50years or below have zero risk of HCC after HBsAg seroclearance, whereas female patients aged above 50years and all male patients are still at risk of HCC. Lay summary: We investigated 4,568 patients with hepatitis B surface antigen (HBsAg) seroclearance. Female patients aged 50years or below have zero risk of hepatocellular carcinoma (HCC) after HBsAg seroclearance, whereas female patients aged above 50years and all male patients are still at risk of HCC.