MODERATE VIRAL LOAD IS ASSOCIATED WITH THE HIGHEST HEPATIC FIBROSIS SCORES IN NON-CIRRHOTIC CHRONIC HEPATITIS B PATIENTS

초록

Background: Non-invasive liver fibrosis scores are used as a validated prognostic biomarker to predict hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. A recent study incorporating wider and more stratified hepatitis B virus (HBV) DNA levels showed that moderate levels of serum HBV DNA are associated with a higher HCC risk. However, the association of HBV DNA levels with non-invasive liver fibrosis scores is unclear. Methods: A historical cohort of 6,949 treatment-naïve, non-cirrhotic Korean CHB patients (2,081 HBeAg-positive; 4,868 HBeAg-negative) with no significant alanine aminotransferase (ALT) elevation (<x2 upper limit of normal) for >1 year was recruited. One-way analysis of variance with Tukey's post hoc test was used for the analysis. Results: During 8.0 years of median follow-up, 363 patients (5.2%) developed HCC. The platelet counts of <150×1000/mm3, APRI scores ≥0.5, and FIB-4 scores ≥1.45 were associated with a higher risk of HCC (P<0.001). Among HBeAg-negative patients, as HBV DNA levels increased, platelet counts decreased, but APRI and FIB-4 scores increased incrementally. In contrast, among HBeAg-positive patients, as HBV DNA levels increased, platelet counts increased, but APRI and FIB-4 scores decreased incrementally. In the entire HBeAg-negative and -positive patients, HBV DNA levels showed a parabolic association with platelet counts, APRI, and FIB-4 scores. Moderate HBV DNA levels (6–7 log10 IU/mL) were associated with the lowest platelet counts (mean 175 k/mm3), but with the highest APRI and FIB-4 scores. Conclusion: Given that non-invasive liver fibrosis scores are validated prognostic biomarkers to predict HCC risk, our findings showing that moderate HBV DNA levels had low platelet counts and high APRI and FIB-4 scores indicate moderate HBV DNA levels are associated with a high risk of HCC even without significant ALT elevation.