Plasma adipocyte fatty acid=binding protein and adiponectin levels are associated with fibrosis regression in nucleoside analogue-treated chronic hepatitis B: a prospective study with paired transient elastography

Abstract

Background and Aims: Nucleoside analogue therapy (NA) can lead to fibrosis regression in chronic hepatitis B (CHB). Nonetheless, emerging evidence is demonstrating the impact of metabolic parameters on the fibrogenic process in CHB. We aim to study the association between adipokine levels and fibrosis evolution in NAtreated CHB patients. Method: NA-treated CHB patients were recruited for baseline and 3-year transient elastography. Fibrosis stages was defined based on EASL-ALEH guidelines. Fibrosis regression and progression were defined as decrease or increase of ≥1 fibrosis stages from baseline respectively. Steatosis was defined as controlled attenuation parameter (CAP) ≥248 dB/m. Plasma adipokines including adiponectin, adipocyte fatty acid-binding protein (AFABP) and fibroblast growth factor 21 (FGF21) were measured by enzyme linked immunosorbent assay at baseline (Antibody and Immunoassay Services, The University of Hong Kong). Results: 404 patients were recruited (72% male; median age 58.6 years; median NA treatment duration 74.5 months). 92.3% and 93.9% of patients had undetectable HBV DNA (≤20 IU/mL) at baseline and reassessment. Median adiponectin, AFABP and FGF21 levels were 10.4 (6.7–17.1) μg/ml, 96.5 (28.4–172.3) pg/ml and 12.6 (7.2–37.0) pg/ml respectively. Patients with steatosis, when compared with nonsteatotic patients, had higher AFABP (117.0 vs 85.4 pg/ml), higher FGF21 (15.4 vs 10.2 pg/ml) and lower adiponectin (8.6 vs 13.3 μg/ml) (all p < 0.05). Patients with advanced fibrosis/cirrhosis had lower FGF21 (11.3 vs 13.6 pg/ml, p = 0.045) and higher AFABP (123.1 vs 69.1 μg/ml, p < 0.001) when compared with non-fibrotic patients. 17.8% of patients had fibrosis progression, while 21.8% of patients had fibrosis regression. Baseline FGF21, body mass index and metabolic syndrome were not predictive of fibrosis evolution. Among patients with advanced fibrosis/cirrhosis at baseline, lower levels of AFABP were independently associated with fibrosis regression (odds 1.005, 95% CI 1.001–1.010). Change in liver stiffness over 3 years correlated moderately with AFABP (r = 0.308, p < 0.001). In the diabetic subgroup, adiponectin was an independent predictor of fibrosis regression (odds 1.296, 95% CI, 1.108–1.516, p = 0.001). Conclusion: Adipokines including AFABP and adiponectin have prognostic value as biomarkers of fibrosis evolution during the treatment course of CHB, further illustrating the influence of metabolic factors in CHB-related treatment outcomes.