As per study report, many patients with chronic hepatitis B (CHB) are categorized as undefined patients because they fall outside the defined CHB phases. Hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-negative patients are considered to be in indeterminate phase. But the concern is whether the risk could be stratified by serum levels of hepatitis B core-related antigen (HBcrAg) or not.

Two retrospective groups enrolling HBeAg-negative, treatment- naive CHB patients without cirrhosis were made (N = 2,150 in Taiwanese discovery group and N = 1,312 in Japanese validation group with a mean follow-up period of 15.88 and 12.07 years, respectively). The primary end point of the study was HCC development.

According to the American Association for the Study of Liver Disease guidelines, 990 (46%) HBeAg-negative patients had indeterminate CHB phase at baseline in the Taiwanese group. When the result was compared with the patients with inactive CHB and those with immune-active CHB, the indeterminate patients exhibited intermediate but diverse risk of HCC. When HCC risk was stratified by a HBcrAg level of 10,000 U/mL, 10-year HCC cumulative incidence was found to be 0.51% and 5.33% for low HBcrAg and high HBcrAg groups, respectively, with a hazard ratio of 4.47 (95% confidence interval: 2.62-7.63). This cutoff was validated to stratify HCC risk not only in different subgroup analyses but also in an independent Japanese cohort. Finally, the overall HBeAg-negative CHB patients could be simply reclassified into high-risk and low-risk groups by combining Alanine Aminotransferase, hepatitis B virus DNA, and HBcrAg levels in both groups. And it was concluded that the serum HBcrAg level of 10,000 U/mL stratifies HCC risk in HBeAg-negative patients with indeterminate phase, which is useful for optimizing their clinical management.

Source: Tai-Chung et al., Am J Gastroenterol. 2022 May 1;117(5):748-757.