Serum Beta-Klotho as a damage-related biomarker in chronic hepatitis B: Correlations with non-invasive fibrosis and inflammation indices

Background Chronic hepatitis B (HBV) infection causes significant morbidity. Liver biopsy, the gold standard for fibrosis assessment, is invasive, highlighting the need for non-invasive biomarkers. β-Klotho, a transmembrane protein, may be released during hepatocyte injury. This study aimed to evaluate serum β-Klotho in treatment-naïve chronic HBV patients and its correlation with inflammation and fibrosis indices. Methods Sixty-seven treatment-naïve HBV patients were divided by viral load (<10⁵ IU/mL, n=34; ≥10⁵ IU/mL, n=33), with 18 healthy controls. Serum β-Klotho was measured via ELISA. Inflammation indices (SII, SIRI, PLR, NLR, LMR, PNR) and non-invasive fibrosis indices (APRI, GAPI, API, PAPAS, others) were calculated. Spearman correlation and ROC analysis were performed. Results Median serum β-Klotho levels tended to be higher in patients with increased HBV DNA levels; however, no statistically significant difference or correlation was observed ( p =0.052; p =0.813). Positive correlations were found with SIRI (r=0.389, p =0.001) and GAPI (r=0.270, p =0.027), negative with LMR (r=-0.269, p =0.028) and PNR (r=-0.322, p =0.008). ROC analysis showed limited diagnostic value (AUC=0.674, p =0.024), with high specificity (94.4%) but low sensitivity (46.3%). No correlation with fibrosis stage was observed. Conclusions Serum β-Klotho tends to increase with viral load, reflecting hepatocellular injury and systemic inflammation rather than established fibrosis. It may serve as a novel non-invasive damage-associated biomarker in chronic HBV, though diagnostic sensitivity is limited.