Association of adipokines with hepatic steatosis and fibrosis in chronic hepatitis B patients on long-term nucleoside analogue

Background & Aims It is unknown how concomitant hepatic steatosis affects disease progression in chronic hepatitis B (CHB). Adipokines such as fibroblast growth factor 21 (FGF21) and adipocyte fatty acid-binding protein (AFABP) have been associated with non-alcoholic fatty liver disease. We determined the significance of these metabolic markers in CHB-related liver injury. Methods We recruited CHB patients on antiviral treatment for transient elastography assessment to determine liver stiffness (advanced fibrosis/cirrhosis, F3/F4, defined by EASL-ALEH criteria) and controlled attenuation parameter (hepatic steatosis, defined as >= 248 dB/m). Plasma FGF-21, AFABP and adiponectin levels were measured. Results A total of 415 patients [mean age 59.6 years, 71.6% male, median treatment duration 6.2 years] were recruited. Patients with F3/F4 (N = 151) had lower FGF-21 (11.7 vs 13.6 pg/mL, P = 0.055), higher AFABP (126.8 vs 84.1 pg/mL, P < 0.001) and HOMA-IR (7.1 vs 5.1, P = 0.004) levels compared to those without F3/F4 (N = 264). Multivariate analysis showed that FGF-21 level was associated with hepatic steatosis (OR 1.005, 95% CI 1.001-1.009) and F3/F4 (OR 0.993, 95% CI 0.989-0.998), while AFABP level (OR 1.001, 95% CI 1-1.002), body mass index (BMI) (OR 1.107, 95% CI 1.037-1.182) and presence of diabetes mellitus (OR 2.059, 95% CI 1.206-3.516) were associated with F3/F4. With the combined presence of BMI >= 25 kg/m(2), diabetes and AFABP > 105.9 pg/mL, the odds ratio for F3/F4 was 3.712 (95% CI 1.364-10.105, P = 0.010). Conclusions Low FGF-21 and high AFABP levels were associated with advanced fibrosis/cirrhosis in CHB patients on antiviral treatment. Plasma AFABP, together with other metabolic risk factors, may aid identification of patients lacking fibrosis improvement during antiviral treatment.