Huang DQ, Li X, Le MH, et al. - Since many patients with chronic hepatitis B (CHB) do not adhere to any of the defined phases and are therefore classified as indeterminate, researchers conducted this retrospective cohort study to describe the baseline prevalence of indeterminate patients and their natural history, phase transition, and risk for hepatocellular carcinoma (HCC). The sample consisted of 3,366 adult untreated non-cirrhotic CHB patients who had at least 1 year of serial laboratory data before registration with a mean follow-up of 12.5 years who were seen at five US clinics and seven Taiwanese townships. One thousand three hundred three (38.7%) patients were in the indeterminate phase at baseline and half of these remained indeterminate and one-fifth transitioned to the immune active phase by up to year 10 of follow-up. The chance of HCC was 14 times higher for persistently indeterminate CHB vs inactive CHB. Age ≥ 45 years was associated with 18 times higher risk for HCC development among persistently indeterminate CHB patients.