HBcrAg may predict HCC development

By Shreeya Nanda

Research suggests a role for hepatitis B core-related antigen (HBcrAg) in the prediction of hepatocellular carcinoma (HCC) development in nucleos(t)ide analogue treatment-naïve patients with chronic hepatitis B virus (HBV) infection.

Researcher Toshifumi Tada (Ogaki Municipal Hospital, Japan) and team say that HBcrAg is "superior to HBV DNA [- a previously reported HCC risk predictor -] in terms of predictive power for HCC development."

But they stress the need for further prospective studies in community-based cohorts and patients who have received nucleos(t)ide analogue therapy.

During a median follow-up of 10.7 years, 78 of 1031 chronic HBV patients included in this medical review were diagnosed with HCC. The cumulative incidence rate of HCC was 2.0% at 5 years, rising to 8.3%, 10.7% and 12.5% at 10, 15 and 20 years, respectively.

Multivariate analysis taking into account various virus-related markers, such as HBV genotype and HBV DNA levels, showed that HBcrAg levels over 2.9 log U/mL predicted HCC development with a significant hazard ratio (HR) of 5.05 (p<0.001). The only other factor significantly associated with HCC progression was the presence of basal core promoter mutations (HR=28.85; p<0.001).

The cumulative incidence of HCC among patients with HBcrAg levels above 2.9 log U/mL and a basal core promoter mutation ranged from 6.4% at 5 years to 34.4% at 20 years, significantly higher than among their wild-type counterparts with HBcrAg levels at or below the cutoff, in whom it was 0.0% at all timepoints (p<0.001).

The accuracy of HBcrAg to predict HCC incidence, as estimated by time-dependant receiver operating characteristic analysis, was higher than for HBV DNA at all timepoints, at, for instance, 80% versus 75% at 2 years and 70% versus 65% at 10 years.

The authors conclude in the Journal of Hepatology that the "[e]levation of HBcrAg levels in [chronic HBV] patients is associated with the development of HCC", adding that in their view "HBcrAg is an excellent predictor" of progression to HCC.

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