Natural History and Clinical Outcomes of HBeAg-Negative Chronic Hepatitis B Patients in the “Grey Zone”: A Longitudinal Cohort Study

Introduction and Objectives: Up to one-third of treatment-naïve, HBeAg-negative chronic hepatitis B (CHB) patients with normal ALT do not meet the strict criteria for the inactive carrier (IC) phase, falling into a “Grey Zone” (GZIC). We aimed to delineate the longitudinal outcomes of GZIC patients compared with strictly defined IC patients. Patients and Methods: This retrospective cohort study included 386 HBeAg-negative, ALT-normal CHB patients (125 GZIC, 261 IC). Endpoints included phase transition to immune-active stages, antiviral initiation, and end-stage liver disease (cirrhosis or hepatocellular carcinoma (HCC)). Cumulative incidence was assessed using Kaplan–Meier analysis.