[Analysis and significance of HBV DNA below the lower detection limit of HBV RNA levels after long-term NAs antiviral therapy in patients with hepatitis B virus cirrhosis]

Objective: To analyze the significance of HBV DNA below the lower detection limit of HBV RNA levels after long-term nucleos(t)ide analogues (NAs) antiviral therapy in patients with hepatitis B virus cirrhosis. Methods: 97 cases with hepatitis B virus cirrhosis treated with NAs antiviral therapy for at least 3 years between May 2018 to July 2019 were selected. High-sensitivity HBV DNA (<20 IU/ml), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), HBsAg, HBeAg and HBV RNA at least twice every 6 months were detected. According to Child-Pugh classification, HBeAg, HBsAg level, and HBV RNA level intergroup comparison was performed. Rank sum test, χ² test and linear regression analysis were performed on the data. Results: Compared with the HBV RNA level of child-Pugh class A patients, the HBV RNA level of Child-Pugh class B+C patients were significantly higher [4.1 (0,4.9) log₁₀ copies/ml and 2.0 (0,3.5) log₁₀ copies/ml], and the difference was statistically significant (Z=2.370, P<0.05). According to different HBeAg levels, they were divided into HBeAg positive and negative group, and the quantitative comparison of HBV RNA levels between the two groups were 2.0 (0, 4.5) log₁₀ copies/ml and 1.0 (1.0, 2.0) log₁₀ copies/ml, respectively, and the difference was statistically significant (Z=3.233, P<0.05). According to different HBsAg levels, they were divided into three groups: HBsAg≤100 IU/ml, 100<HBsAg<1 000 IU/ml, and HBsAg≥1 000 IU/ml, and the quantitative comparison of HBV RNA levels among the three groups were 0 (0, 2.0) log₁₀, 2.0 (0,4.6) log_10, and 2.2 (2.0, 4.7) log₁₀ copies/ml, respectively, and the difference was statistically significant (H=11.265, P<0.05). Gender, age, ALT, AST, GGT, HBsAg, and HBeAg were included for linear regression analysis, and the HBsAg and AST levels were correlated with HBV RNA quantification (P<0.05). Adverse events occurrence during 1-year follow-up were recorded. 19 (31.7%) out of 60 cases had adverse events with detectable HBV RNA, and 3 (8.1%) out of 37 cases had adverse events with undetectable HBV RNA, and the difference was statistically significant (χ²=7.24, P<0.05). Conclusion: HBV RNA can still be detected after HBV DNA falls below the detection limit in patients with hepatitis B virus cirrhosis treated with long-term NAs antiviral therapy. HBV RNA quantification level is higher in patients with Child Pugh class B and C. Patients with detectable HBV RNA has higher proportion of adverse events, and AST and HBsAg levels may be correlated with serum HBV RNA.