Classification of virologic trajectories during nucleos/tide analogue treatment of hepatitis B virus (HBV) infection

Abstract

Background & AimsThe dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos/tide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes.MethodsUtilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment. We assessed associations of VL trajectory with alanine transaminase (ALT), and with liver fibrosis/cirrhosis.ResultsWe retrieved data from 1885 adults on NA treatment (median follow-up 6.2 years, interquartile range (IQR) 3.7-9.3 years), with 21,691 VL measurements (median 10 per patient, IQR 5-17). Five VL classes were identified from the derivation cohort (n=1367, discrimination: 0.93, entropy: 0.90): class 1 ‘long term suppression’ (n=827, 60.5%), class 2 ‘timely virological suppression’ (n=254, 18.6%), class 3 ‘persistent moderate viraemia’ (n=140, 10.2%), class 4 ‘persistent high-level viraemia’ (n=44, 3.2%), and class 5 ‘slow virological suppression’ (n=102, 7.5%). The model demonstrated a discrimination of 0.93 and entropy of 0.88 for the validation cohort (n=518). ALT decreased variably over time in VL-suppressed groups (classes 1, 2, 5; all p<0.001), but did not significantly improve in those with persistent viraemia (classes 3, 4). Patients in class 5 had 2-fold increased hazards of fibrosis/cirrhosis compared to class 1 (adjusted hazard ratio, 2.00; 95% CI, 1.33-3.02).ConclusionsHeterogeneity exists in virological response to NA therapy in CHB patients, with over 20% showing potentially suboptimal responses. Slow virological suppression is associated with liver disease progression.