Role of quantitative hepatitis B core antibody levels in predicting significant liver inflammation in chronic hepatitis B patients with normal or near-normal alanine aminotransferase levels

Aim: Chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) levels are not free from significant hepatic lesions. Recently, there has been an improved understanding of the clinical significance of quantitative hepatitis B core antibody levels (qAnti-HBc) during CHB management. In this cross-sectional study, we evaluated the utility of qAnti-HBc in identifying significant liver inflammation in CHB patients. Methods: A total of 469 patients (training set, n=363; validation set, n=106) who underwent liver biopsy (LB) were included. The qAnti-HBc levels were quantified and the relationship between histology and serum markers was systematically analyzed. Results: In the training set, qAnti-HBc levels were found to have significant diagnostic value for moderate to severe liver inflammation (>= G2) in all patients (area under the receiver operating characteristic curve [AUROC]=0.768; 95% confidence interval [CI], 0.721-0.810; P<0.001) and in patients with normal or near-normal ALT levels (AUROC=0.767; 95% CI, 0.697-0.828; P<0.001). Our novel index (AC index) for the identification of >= G2 inflammation, which combined the qAnti-HBc and ALT levels, significantly improved diagnostic performance (AUROC=0.813; 95% CI, 0.768-0.852) compared to the use of ALT alone (AUROC=0.779; 95% CI, 0.732-0.821) in all patients. In the validation set, the AC index showed an improved AUROC of 0.890 (95% CI, 0.814-0.942) and 0.867 (95% CI, 0.749-0.943) in all patients and patients with normal ALT levels, respectively. Conclusions: The qAnti-HBc level predicts significant liver inflammation well, even in patients with normal or near-normal ALT levels. Compared with the conventional ALT level, the AC index is a more reliable non-invasive biomarker for significant liver inflammation in CHB patients.