Histologic Disease in Chinese Chronic Hepatitis B Patients With Low Viral Loads and Persistently Normal Alanine Aminotransferase Levels

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We aimed to evaluate the histopathologic characteristics of HBeAg-negative chronic hepatitis B patients with low hepatitis B virus (HBV) DNA levels (<2000 IU/mL) and persistently normal ALT levels and to determine indicators of significant liver disease.


We examined 102 consecutive subjects who underwent percutaneous liver biopsy. Significant predictors of liver disease (stage ≥2 fibrosis or stage 1 fibrosis plus grade ≥2 inflammation), including demographic, clinical, and laboratory variables, were evaluated by means of univariate and multivariate logistic regression analyses.


Among the patients, 75.5% (77/102) had grade 0-1 inflammation and 77.5% (79/102) had stage 0-1 fibrosis. However, 38.2% (39/102) had significant liver disease. There were no statistically significant differences in clinical parameters such as age, biochemical profile, HBV DNA levels, HBsAg levels, and platelet count between patients with significant and those with nonsignificant liver disease. Patients with significant liver disease had higher values of aspartate transferase-to-platelet ratio index (APRI) and FIB-4 index compared with those with nonsignificant liver disease (0.35±0.21 vs. 0.27±0.12, P=0.02; 1.58±0.97 vs. 1.13±0.54, P=0.009, respectively). The area under the receiver operating characteristic (AUROC) curve of APRI for identifying active liver histology was 0.64 (95% CI, 0.53-0.75; P=0.019); the cutoff value was 0.24 with a sensitivity of 74% and specificity of 55%. In comparison, FIB-4 had equal power (the AUROC was 0.66) in predicting active liver histology.


Among patients presenting with low HBV DNA levels and normal ALT levels, about 38.2% had significant liver disease. Neither serum HBsAg nor HBV DNA levels correlate with liver histology. However, APRI≥0.24 might be considered an indicator of liver biopsy.

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