Determinants of persistent significant fibrosis during long-term nucleoside analogue therapy in chronic hepatitis B: an interim analysis

Abstract

Background: Changes in liver stiffness measurements (LSM) during long-term nucleoside analogue therapy in chronic hepatitis B (CHB) have not been well-investigated. Methods: We recruited CHB patients on long-term nucleoside analogue herapy with persistent virologic suppression (HBV DNA <20 IU/ml on 3 occasions of at least 6 months apart) and with previous LSM indicating significant liver fibrosis, as defined by EASL-ALEH Guidelines (>9.0 kPa for normal alanine aminotransferase [ALT] and >12.0 kPa for ALT >1-5 x upper limit of normal). Assessment included anthropometric measurements, HBV virology, and reassessment transient elastography and controlled attenuation parameter (CAP) measurements by FibroScan® (Echosens, Paris, France). Hepatic steatosis was defined as CAP ~222 dB/m. Results: In this interim analysis, 119 CHB patients (77.3% male) were recruited. Mean age at reassessment and mean duration of nucleoside analogue therapy was 56.1 (±10.4) years and 8.5 (±3.1) years respectively. 38 patients (31.9%) had persistent liver fibrosis. Patients with persistent liver fibrosis, when compared to patients with fibrosis reversal, had a significantly higher mean body-mass index (26.0 kg/m2 and 23.6 kg/m2 respectively, p=0.040), mean systolic blood pressure (144 mmHg and 136 mmHg respectively, p=0.029) and mean diastolic blood pressure (82 mmHg and 77 mmHg respectively, p=0.046). There was no significant difference in the presence of hepatic steatosis among the two groups (65.8% and 55.6% respectively, p=0.290). Conclusion: Metabolic parameters, including body-mass index and blood pressure, could influence fibrosis reversibility during long-term nucleoside analogue therapy. Recruitment is ongoing and the influence of other metabolic parameters (e.g. metabolic syndrome) will be analyzed.