Higher risk of disease progression in the grey zone relative to inactive Chronic hepatitis B

Background: & aims： Chronic hepatitis B (CHB) remains a global healthcare burden. Inactive CHB(IC) is the commonest immune state. However, there are some patients with normal alanine aminotransferase (ALT)and HBeAg negativity that cannot be clearly defined by the guidelines, which called the Grey zone corresponding to IC(GZIC). There is still confusion about the evolution of disease progression in the GZIC. So we aimed to study the natural history and antiviral treatment of IC and GZIC. Method: This was a retrospective-prospective cohort study that included 300 patients with stage IC and GZIC. Conversion to HBeAg-negative immune-active CHB (IA) and IA corresponding grey zone (GZIA), initiation of antiviral therapy, and occurrence of end-stage liver disease events were defined as outcome events. The cumulative incidence of outcome events in the IC and GZIC groups was compared. Results: At baseline, 201 (67.00%) patients were IC and 99 (33.00%) were GZIC.18.9% of the 300 patients with IC and 46.4% of the patients with GZIC converted to IA or GZIA.30(10%) received antiviral therapy, of which 22 (77.3%) were patients with GZIC and 8 ( 22.7%) were IC patients. Nine (3%) developed end stage liver disease of which seven (77.78%) were GZIC and two (22.22%) were IC. The cumulative event rates for conversion to IA or GZIA, initiation of antiviral therapy, and occurrence of end-stage liver events were higher in GZIC than in IC (p < 0.0001, p < 0.0001, p = 0.0018). Conclusion: Patients with GZIC have a higher risk of disease progression than those with IC.