Huang DQ, Li X, Le MH, et al. - This study was attempted to define the baseline prevalence of indeterminate chronic hepatitis B (CHB) patients and their natural history, phase transition, and hepatocellular carcinoma (HCC) risk. Researchers performed a retrospective cohort study including a total of 3,366 adults untreated non-cirrhotic CHB patients seen at five US clinics and seven Taiwanese townships with at least one year of serial laboratory data before enrollment with a mean follow-up of 12.5 years. They ascertained patients’ clinical phases at baseline and through serial data during follow-up, based on the AASLD 2018 Guidance. It was shown that nearly 40% of patients had an indeterminate CHB phase. Among these, half stayed indeterminate and one-fifth moved to the immune active phase. Results demonstrated that HCC risk in persistently indeterminate CHB was 14 times higher than inactive CHB. Age ≥ 45 years was correlated with an 18 times higher risk for HCC development among persistently indeterminate CHB patients. Further trials are required to assess the potential benefit of antiviral therapy for indeterminate patients, especially in the older subgroup.