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Background and Aims: Chronic hepatitis B (CHB) is a major cause of cirrhosis and end-stage liver disease. Not all patients with CHB require antiviral treatment but long-term monitoring is critical to identify patients who would benefit from antiviral therapy. CHB patients followed in various clinical settings may differ in disease characteristics and rates of treatment eligibility in long-term follow-up.Methods: We conducted a retrospective cohort study of 359 consecutive treatment-naive, treatment-ineligible CHB patients (228 from community GI clinics; 73 from university hepatology clinic; 58 from primary care clinic). Primary end points were the proportion of patients meeting eligibility criteria in follow-up, and the eligibility comparison among patients in various clinical settings. Univariate and multivariate Cox's proportional hazard models were used to calculate hazard ratios to identify predictors of treatment eligibility in follow-up.Results: While the majority of patients remained treatment ineligible by guideline recommendations, a sizeable proportion (23 %, 95 % CI 18-27 %) of patients subsequently met treatment eligibility in study follow-up. Reasons for meeting US Panel treatment eligibility on multivariate analysis included baseline ALT ≥ ULN (HR 1.91, p = 0.03) and baseline HBV DNA ≥ 2000 IU/mL (HR 2.6, p = 0.001). Practice setting was not a predictor.Conclusions: A significant number of patients with CHB (23 %) who were not initially treatment eligible later met treatment criteria in longer-term follow-up. Significant independent predictors of treatment eligibility included a baseline ALT ≥ ULN and elevated HBV DNA (≥2000 IU/mL for US Panel eligibility and ≥20,000 IU/mL for AASLD eligibility). This study underscores the importance of long-term follow-up for patients with CHB. [ABSTRACT FROM AUTHOR]