Distribution and clinical characteristics of patients with chronic hepatitis B virus infection in the gray zone
Kefang Yao 1 , Jiacheng Liu 2 , Jian Wang 3 , Xiaomin Yan 3 , Juan Xia 3 , Yue Yang 3 , Weihua Wu 3 , Yong Liu 4 , Yuxin Chen 4 , Zhaoping Zhang 3 , Jie Li 5 , Rui Huang 3 , Chao Wu 1 2 3
Affiliations
Affiliations
1
Department of Infectious Diseases, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing Jiangsu, China.
2
Department of Infectious Diseases, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing Jiangsu, China.
3
Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing Jiangsu, China.
4
Department of Laboratory Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing Jiangsu, China.
5
Department of Infectious Disease, Shandong Provincial Hospital affiliated to Shandong University, Ji'nan Shandong, China.
PMID: 33797145 DOI: 10.1111/jvh.13511
Abstract
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 "gray zones ". We aimed to investigate the distribution and characteristics of this gray zone 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. Gray zone CHB patients were classified into 4 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 gray zone. 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 gray zone CHB patients. Therefore, our results revealed that more than a quarter of CHB patients were classified into the gray zone and a high proportion of patients in GZ-B had advanced fibrosis or even cirrhosis.