ABSTRACT
Objective:To investigate the relationship and diagnostic value of serum hepatitis B virus(HBV) RNA on liver significant inflammation in chronic hepatitis B (CHB)patients with normal or mildly elevated alanine transaminase (ALT) levels.Methods:A total of 211 treatment-naive CHB patients with ALT<two times of the upper limit of normal in Shanghai Public Health Clinical Center, Fudan University between January 2016 and June 2019 were retrospectively studied.All of them received liver biopsy. Serum HBV RNA levels were quantified by quantitative reverse transcription polymerase chain reaction. Statistical analyses were performed with t test, Mann-Whitney U test, chi-square test and logistic regression analysis. Results:In 83 hepatitis B e antigen (HBeAg)-positive patients, the serum HBV RNA levels decreased with the increasing severity of liver inflammation ((6.208±1.363) lg copies/mL vs (4.654±0.962) lg copies/mL, t=6.035, P<0.01). In 138 HBeAg-negative patients, the serum HBV RNA levels increased with the increasing severity of liver inflammation ((3.101±0.720) lg copies/mL vs (3.965±0.782) lg copies/mL, t=-5.892, P<0.01). Logistic regression analysis showed that serum HBV RNA level was an independent predictor for significant liver inflammation (odds ratio ( OR)=0.168, P=0.003) in HBeAg-positive patients. Area under receiver operator characteristic curve (AUROC) was 0.82 (95% confidence interval ( CI) 0.73-0.91) of HBV RNA and 0.56(95% CI 0.44-0.69) of ALT for the diagnosis of significant liver inflammation. The difference was statistically significant ( z=2.975, P=0.003). Serum HBV RNA ( OR=4.960, P<0.01), γ-glutamyl transpeptidase ( OR=1.021, P=0.019) and blood platelet (PLT) ( OR=0.987, P=0.008) were independent predictors for significant liver inflammation in HBeAg-negative patients. The AUROC of HBV RNA and ALT was 0.78(95% CI 0.69-0.87) and 0.65(95% CI 0.55-0.75), respectively. The AUROC of combination diagnostic model consisting of HBV RNA, γ-glutamyl transpeptidase and blood platelet was 0.86(95% CI 0.79-0.93) for the diagnosis of significant liver inflammation. Conclusions:The serum HBV RNA levels are significantly different among the different phases of liver inflammation in treatment-naive CHB patients with normal or mildly elevated ALT levels. Inflammation-related serum HBV RNA and combination diagnostic model are expected to be the novel non-invasive diagnostic biomarkers for significant liver inflammation and of great benefit for determining the time for clinical medication of treatment-naive CHB patients.