Age And E Antigen Status Are Associated With Pre-Existing Tolerance Mutations In Chinese Patients With Chronic Hbv Infection: A Retrospective Case Control Study

Background: The aim of this study was to investigate prevalent mutations of RT region of hepatitis B virus (HBV) genome in NA naive Chinese patients with chronic HBV infection. Methods: A total of 217 patients with chronic HBV infection (172 with chronic hepatitis B and 45 with liver cirrhosis) were enrolled in this study. Mutations were detected by the direct sequencing of RT region after PCR amplification. Mutations and subsequent amino acid changes were analyzed for 16 well characterized NAs-resistance mutations (rtL180M, rtA181T/V/S, rtT184A/G/I/S, rtS202G/I, rtM204V/I/S, rtN236T and rtM250V/L) and 10 secondary or compensatory resistance mutations (rtV173L, rtV207I/L/G, rtS213T, rtV214A, rtQ215S, rtP237H and rtN/H238T/D). Results: Out of the 217 patients, 151 (69.6%) were male and 67 (30.4%) were female. A total of 166 patients (76.5%) were HBeAg positive. Mutations in the RT region were found in 28 patients (12.9%) including 34 mutations. Primary resistance mutations of HBV RT region were found in 8 (3.7%) cases. Of these 8 patients, 6 had rtM204I including 2 with combination of rtL180M, 1 had rtA181T and 1 had rtT184S substitution. While secondary/compensatory resistance mutations were detected in 20 (9.2%) cases. The most frequent secondary resistance mutation was rtS213T (5.0%), followed by rtV214A/E/P (2.3%) and rtV207L/M/I (1.8%). Multivariate analysis showed that age (P=0.021) and HBeAg status (P<0.001) were associated with HBV resistance mutations, while sex, ALT, AST, TBIL, HBV DNA level, genotype and liver disease stages were not statistically significant. Conclusions: Primary resistance mutations can be detected in treatment naive HBV infected patients, especially in older and HBeAg negative ones. Antivirals with high genetic barriers should be selected to avoid potential treatment failure.