Yuen L, Revill PA, Rosenberg G, et al. - In individuals with chronic hepatitis B (CHB), progression of liver fibrosis reduces with nucleos(t)ide analouges (NUC) treatment. However, despite viral suppression, risk for hepatocellular carcinoma (HCC) persists. Given an association of specific HBV variants with adverse outcomes, including HCC, researchers sought to determine the frequency of clinically relevant viral variants via performing next generation sequencing and detailed virological characterization on a cohort of treatment‐naïve  immunotolerant (IT) individuals. They analyzed samples from 97 individuals (genotype B/C 55%/45%, median HBV‐DNA 8.5 log10 IU/mL, median HBsAg 4.8 log10IU/mL, median HBeAg 3.6 log10 PEIU/mL). Clinically relevant HBV variants were commonly identified at baseline, particularly in the basal core promoter (BCP, overlaps the hepatitis B X (HBx) gene), precore, and PreS regions despite individuals being in the IT phase. Independent association was observed of BCP/HBx variants with lower baseline HBeAg, HBsAg and HBV‐DNA titres. Indepndent association was observed of precore variants with higher baseline ALT. With increased age and lower HBV DNA, HBsAg and HBeAg levels, they observed increased viral diversity.