Trajectories of serum hepatitis B surface antigen kinetics in patients with chronic hepatitis B receiving long‐term nucleos(t)ide analogue therapy

Background & Aims The kinetics of serum hepatitis B surface antigen ( HB sAg) levels during long‐term nucleos(t)ide analogue ( NA ) therapy in chronic hepatitis B ( CHB ) patients remains unclear. We investigated the patterns of serum HB sAg kinetics and their association with therapeutic outcomes in genotype B‐ or C‐infected CHB patients receiving long‐term NA therapy. Methods We enrolled 329 treatment‐naive CHB patients receiving NA therapy for >5 years to analyse the kinetic patterns by using group‐based trajectory models ( GBTM s). Results Most patients (82.4%) received entecavir therapy. The median treatment duration was 83.6 (68.5‐89.7) months. The GBTM s revealed three groups for both the hepatitis B e antigen ( HB eAg)‐positive and ‐negative patients. The median annual decline in serum HB sAg levels during the first 5 years was significantly higher in Group 1 than in Groups 2 and 3 in HB eAg‐positive (0.78 vs 0.10 vs 0.10 log 10 IU/mL) and HB eAg‐negative (0.71 vs 0.08 vs 0.09 log 10 IU/mL) patients. HB sAg levels at the baseline and 12 months combined with an HB sAg decline from the baseline to 12 months of treatment predicted trajectory pattern 1 in HB eAg‐positive (sensitivity, 77.8%; specificity, 99.1%; positive predictive value [ PPV ], 87.5%; and negative predictive value [ NPV ], 98.2%) and HB eAg‐negative (sensitivity, 100%; specificity, 99.5%; PPV , 88.9%; and NPV , 100%) patients. The trajectory patterns were significantly associated with HB eAg loss in the HB eAg‐positive patients and the achievement of HB sAg <100 IU/mL or HB sAg loss in HB eAg‐positive and HB eAg‐negative patients. Conclusions The trajectory of serum HB sAg levels predicts HB sAg loss in CHB patients receiving long‐term NA therapy.