Serum fibulin-5 shows no independent association with liver stiffness in a pilot cohort of chronic hepatitis B patients

Fibulin‑5 (FBLN5) has been proposed as a serum biomarker for liver fibrosis in chronic hepatitis C, but its value in chronic hepatitis B (CHB) is unknown. This pilot study aimed to investigate whether serum FBLN5 correlates with liver stiffness measurement (LSM) in real‑world CHB patients after controlling for steatosis (controlled attenuation parameter, CAP) and inflammation (ALT). In 52 CHB patients, FBLN5 was not correlated with raw LSM (ρ = 0.021, P = 0.881). Residual‑based method for CAP and ALT also showed no correlation (ρ=−0.028, 95% CI − 0.30 to 0.25, P = 0.844). Sensitivity analyses (median‑split, outlier exclusion) were consistent. FIB‑4, calculated in 36 patients as a positive control, did not reach significance (ρ = 0.275, P = 0.105). Multivariable regression confirmed no independent association between FBLN5 and log‑LSM (adjusted β = 0.00002, 95% CI − 0.000035 to 0.000075, P = 0.473). In this small pilot cohort ( n = 52) with predominantly mild fibrosis (median LSM 6.8 kPa), serum FBLN5 did not show an independent association with LSM. The non‑significant FIB‑4 correlation and the lack of association for CAP and ALT suggest that the most parsimonious explanation is the narrow clinical spectrum of the cohort, rather than biology‑specific failure of FBLN5. Our findings are exploratory and hypothesis‑generating, requiring validation in cohorts enriched with advanced fibrosis.