A substantial proportion of patients with chronic hepatitis B (CHB) who do not fit into any of the usual immune states are considered to be in the ‘grey zone (GZ)’. We aimed to investigate the distribution and characteristics of GZ in a large cohort of CHB patients. Four thousand seven hundred and fifty‐nine consecutive treatment‐naïve CHB patients were enrolled. The immune states were defined based on AASLD 2018 Hepatitis B Guidance. GZ CHB patients were classified into four groups: HBeAg positive, normal ALT levels and serum HBV DNA ≤106 IU/ml (GZ‐A); HBeAg positive, elevated ALT levels and serum HBV DNA ≤2 × 104 IU/ml (GZ‐B); HBeAg negative, normal ALT levels and serum HBV DNA ≥2 × 103 IU/ml (GZ‐C); HBeAg negative, elevated ALT levels and serum HBV DNA ≤2 × 103 IU/ml (GZ‐D). The distributions of different immune states were: 233 (4.90%) patients in immune‐tolerant phase, 941 (19.77%) patients in HBeAg‐positive immune active phase, 1,717 (36.08%) patients in inactive phase and 546 (11.47%) patients in HBeAg‐negative immune active phase. Of note, 1,322 (27.78%) patients did not fit into any of above phases and were defined as the GZ. A high proportion of patients in GZ‐B had advanced fibrosis (33.3%) or cirrhosis (25.8%). Older age, HBeAg‐positive status and higher ALT levels were independently risk factors of advanced disease in GZ CHB patients. Therefore, our results revealed that more than a quarter of CHB patients were classified into the GZ and a high proportion of patients in GZ‐B had advanced fibrosis or even cirrhosis.
Serum hepatitis B core antibody (anti-HBc) is associated with liver inflammation in chronic hepatitis B patients. This study aimed to investigate whether anti-HBc could serve as a predictor of significant liver inflammation in hepatitis B e antigen (HBeAg)negative chronic hepatitis B virus (HBV) infected patients with normal alanine aminotransferase (ALT) and detectable HBV DNA. Treatment-naïve HBeAg-negative chronic HBV infected patients with normal ALT and detectable HBV DNA who underwent liver biopsy were retrospectively included from two medical centers.Liver inflammation grade was evaluated using the Scheuer scoring system and significant liver inflammation was defined as ≥G2. Serum anti-HBc levels were measured by commercial immunoassays (Abbott GmbH & Co. KG). A total of 117 patients were included and 50 (42.7%) patients showed significant liver inflammation. Serum anti-HBc levels in patients with significant liver inflammation were significantly higher than patients with no or mild liver inflammation (
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