BREAKTHROUGHBackground: Little is known about non-adherence to Hepatitis B virus (HBV) therapy.This study aimed to investigate the relationship between self-reported missed days of anti-viral therapy and HBV virological breakthrough and factors associated with virological breakthrough.Methods: A cross-sectional survey of 211 HBV patients receiving oral anti-viral therapies was undertaken at three tertiary hospitals in Sydney, Australia. Associations between 0 to > 6 missed days in the last 30 days and virological breakthrough (defined as > 10-fold rise in serum HBV DNA above nadir or after achieving virological response in the last 12 months) were examined. Logistic regression analyses determined the number of missed days most strongly associated with virological breakthrough and the associated factors. We report odds ratios and relative risks.Results: Of the 204, 32 participants (15.6%) had quantifiable HBV DNA levels (> 20 IU/mL); 15 (46.8%) of them experienced virological breakthrough. Participants reported never missing medication (n=130, 63.7%) or missing one day (n=23, 11.3%), >one day (n=23, 11.3%), 2-6 days (n=15, 7.3%) and >6 days (n=13, 6.4%). The most discriminating definition of non-adherence was missing > one day of medication