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

Abstract

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 (HBsAg). To assess the available evidence about risk factors for HCC after HBsAg 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. HBsAg seroclearance occurred spontaneously in 7656, while it occurred after interferon or nucleos(t)ide analogue therapy in 1248. The rate of HBsAg seroclearance was 6.77%. Incidence of HCC was significantly lower among patients who experienced HBsAg seroclearance than among those who remained HBsAg-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 HBsAg seroclearance (2.34% vs 0.63%) (all P < .001). The available evidence suggests that HCC can develop at a low rate after HBsAg seroclearance, so periodic surveillance is recommended, especially for male patients, patients with cirrhosis and patients who experience HBsAg seroclearance when at least 50 years old.

KASL clinical practice guidelines for management of chronic hepatitis B

“…HBsAg loss is the state of functional cure, and it is associated with a reduced risk of cirrhosis. However, significant risk of HCC development remains even after HBsAg loss in male patients, and in settings where HBsAg loss has been achieved late (presence of cirrhosis or age ≥50 years) [35,36].…”

“…Drug compliance and emergence of antiviral-resistance mutations should be monitored in patients who develop virological breakthrough while receiving NAs, and an appropriate rescue therapy should be initiated if necessary (Fig. 3) [35,79,270-272].…”

The Changing Epidemiology of Primary Liver Cancer

“…As NAs interfere with HBV replication, but do not clear the virus, they are generally prescribed for the person's lifetime. The extent to which inhibition of viral replication will reduce the risk of HCC as yet remains uncertain, although a systematic review found that several factors were associated with risk reduction, including becoming HBV surface antigen seronegative, not having cirrhosis, being younger than 50 years of age and being female [20]. Even among individuals with the greatest number of favorable factors, however, the risk of HCC remains elevated, suggesting that NA-treated persons should remain under surveillance.…”

Life After s Loss: Impact of Hepatitis B s Antigen Loss on Future Patient Outcomes

“…Kuang et al 21 performed a systematic review and meta‐analyses evaluating the risk factors for HCC development after HBsAg loss. The presence of cirrhosis, male sex, and age >50 years at the time of HBsAg loss were significant risk factors for HCC development, and HCC surveillance should be continued in individuals with any of these risk factors.…”