Long‐term outcome of inactive and active, low viraemic HBeAg‐negative‐hepatitis B virus infection: Benign course towards HBsAg clearance

Abstract Background & Aims The difference between the long‐term outcome of low‐viraemic ( HBV ‐ DNA ≤20 000‐ IU / mL , LV ‐ AC ) and inactive HB sAg carriers ( HBV ‐ DNA ≤2000‐ IU / mL , IC ) remains to be defined. We studied prospectively 153 HB eAg‐negative HB sAg‐carriers with baseline HBV ‐ DNA ≤20 000‐ IU / mL and normal transaminases. Methods IC , LV ‐ AC or chronic hepatitis B ( CHB ) ( HBV ‐ DNA persistently ≤2000‐ IU / mL , ≤20 000‐ IU / mL or >20 000‐ IU / mL respectively) were diagnosed after 1‐year, 3‐monthly monitoring. Thereafter IC and LV ‐ AC were followed‐up for additional 57.2 (8.5‐158.3) months. HBV ‐ DNA , HB sAg, HBV ”core‐related”Antigen ( HB crAg) and total‐anti‐ HB c were quantified at baseline. Results After the 1st year diagnostic follow‐up CHB [higher HBV ‐ DNA ( P =.005), total‐anti‐ HB c ( P =.012), ALT ( P =.007) and liver‐stiffness ( P =.021)] was identified in 20 (13.1%) carriers; baseline HB sAg≤1000 IU / HBV ‐ DNA ≤2000 IU / mL excluded the presence of CHB ( NPV ‐100%). Thereafter, during the long‐term follow‐up none of 87 IC reactivated, 19 (21.8%) cleared HB sAg [older‐age ( P =.004), lower HB sAg ( P <.001), higher yearly HB sAg decline ( P <.001)]. Twenty‐five of 46 (54.3%) LV ‐ AC remained stable, 20 (43.5%) became IC and 1 (2.2%) developed CHB . The best single‐point CHB and IC diagnostic‐accuracies were total‐anti‐ HB c (84.2%, NPV ‐98.2%) and HBV ‐ DNA /total‐anti‐ HB c/ HB crAg combination (89.5%, 93%‐sensitivity, 84.8%‐specificity) respectively. Conclusions Viraemia persistently ≤20 000‐ IU / mL predicts a benign clinical outcome: it was associated with transition to IC in 43% of LV ‐ AC and to Occult HBV Infection in 20% of IC within 5‐years. Nevertheless, 13.1% of individuals with low viraemia at presentation develops CHB within 1 year: 1‐year HBV ‐ DNA monitoring resulted the most accurate diagnostic approach that can be limited to at least a half of cases by the single point HBV ‐ DNA / HB sAg quantification. The IC ‐diagnostic‐accuracy combining HBV ‐ DNA /total‐anti‐ HB c/ HB crAg needs to be confirmed in further studies.