Hepatitis B Core-Related Antigen Level Predicts Disease Progression in the Gray Zone Hepatitis B Patients

The natural history of hepatitis B virus (HBV) infection does not always conform to the currently defined phases, and some patients who do not clearly meet established treatment criteria are classified as in the gray zone (GZ). We investigated the factors for progression of hepatitis B e antigen (HBeAg)-negative GZ patients to chronic hepatitis (CH): HBV DNA levels ≥ 3.3 log IU/mL and alanine aminotransferase (ALT) ≥ 31 U/L.

This study included 102 HBeAg-negative GZ patients (81 with high HBV DNA levels and normal ALT levels, and 21 with low HBV DNA levels and high ALT levels), and who underwent liver stiff measurement using transient elastography.

Of 91 patients followed up for more than 6 months, 19 progressed to CH, and the cumulative incidence rate of progression to CH at 5 years was 17.5%. Multivariate analysis showed that only the hepatitis B core-related antigen (HBcrAg) level was independently associated with progression to CH (HR 3.08; p = 0.003). Receiver operating characteristic curve analysis to assess the effectiveness of HBcrAg levels in predicting progression to CH showed the area under the curve was 0.828, and the optimal cut-off value was determined to be 2.87 log U/mL. When applying this cut-off, the cumulative incidence rates of progression to CH were significantly divided (p < 0.001): 5-year rates were 39.1% in patients with HBcrAg levels ≥ 2.87 log U/mL and 2.9% in those with levels < 2.87 log U/mL.

HBcrAg levels are useful for predicting progression to CH by HBeAg-negative GZ patients.

The study protocol was approved by the Institutional Review Board of Nagoya City University (approval number: 60-00-0657).