Systematic review of risk factors of hepatocellular carcinoma after hepatitis B surface antigen seroclearance

Summary There is no consensus about factors that increase risk of hepatocellular carcinoma ( HCC ) among patients with chronic hepatitis B who have achieved seroclearance of hepatitis B surface antigen ( HB sAg). To assess the available evidence about risk factors for HCC after HB sAg seroclearance, Scopus, EMBASE , PubMed and Cochrane Library databases were systematically searched for relevant studies published through 15 September 2017. A total of 28 studies involving more than 105 411 patients with chronic hepatitis B were included. HB sAg seroclearance occurred spontaneously in 7656, while it occurred after interferon or nucleos(t)ide analogue therapy in 1248. The rate of HB sAg seroclearance was 6.77%. Incidence of HCC was significantly lower among patients who experienced HB sAg seroclearance than among those who remained HB sAg‐positive (1.86% vs 6.56%, P < .001). Risk factors of HCC occurrence included cirrhosis (incidence with vs without: 9.51% vs 1.66%), male gender (2.34% vs 0.64%) and age ≥ 50 year at HB sAg seroclearance (2.34% vs 0.63%) (all P < .001). The available evidence suggests that HCC can develop at a low rate after HB sAg seroclearance, so periodic surveillance is recommended, especially for male patients, patients with cirrhosis and patients who experience HB sAg seroclearance when at least 50 years old.