A high level of hepatitis B core-related antigen (HBcrAg) is a complementary risk factor for hepatocellular carcinoma (HCC) development, according to a study published in Gastroenterology.

One of the main causes of death in patients with hepatitis B virus (HBV) infection is HCC; therefore, identifying patients at high risk for HCC is important for providing preemptive antiviral treatment to reduce risk. Serum levels of HBcrAg are associated with active replication of HBV; therefore, the researchers investigated whether HBcrAg levels associate with development of HCC, especially in patients who do not require antiviral treatment. They collected data from 2666 adults positive for hepatitis B surface antigen (HBsAg), infected with HBV genotypes B or C and without liver cirrhosis, who had long-term follow-up at the National Taiwan University Hospital from 1985 through 2000 and did not have antiviral treatment during the follow-up.

They found that in the entire cohort, 209 patients developed HCC (incidence rate, 4.91 cases/1000 person-years), and there was a positive association between baseline of HBcrAg and HCC development. Among patients with an intermediate viral load from 2000 to 19,999 IU/mL, those with a high HBcrAg level (≥10 KU/mL) had an HCC risk close to those with a high viral load (≥20,000 IU/mL), whereas those with a low HBcrAg level had an HCC risk similar to that of minimal risk carriers.

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“In summary, in a cohort of 2666 patients infected with HBV genotypes B or C, baseline HBcrAg level serves an independent risk factor for HCC development,” stated the authors. “Therefore, HBcrAg of 10 KU/mL may serve a novel biomarker for the management of patients with [intermediate viral load] in our clinical practice,” they concluded.


Tseng T-C, Liu C-J, Hsu C-Y, et al. High level of hepatitis B core-related antigen associated with increased risk of hepatocellular carcinoma in patients with chronic HBV infection of intermediate viral load [published online August 27, 2019]. Gastroenterology. doi:10.1053/j.gastro.2019.08.028