Drug resistance mutations in polymerase region and related influencing factors in patients with hepatitis B virus infection

Objective To investigate the pattern of drug resistance mutations of the genes in the reverse transcriptase( RT) region and its association with clinical features in patients with hepatitis B virus( HBV) infection in Xuzhou,Jiangsu,China,as well as the influencing factors for drug resistance. Methods A total of 242 patients with HBV infection who underwent the detection of the HBV RT region in Department of Infectious Diseases,The Affiliated Hospital of Xuzhou Medical University,from May 2014 to April 2019 were enrolled,and the clinical features were compared between the patients with different genotypes and HBeAg statuses. Of all patients,164 had a clear medication history of nucleos( t) ide analogues( NAs),among whom 118 had known mutations at drug resistance loci and 46 did not have such mutations,and the risk factors for drug resistance mutations in the HBV RT region were analyzed for the two groups. The independent samples t-test or the Mann-Whitney U test was used for comparison of continuous data between groups; the chi-square test was used for comparison of categorical data between groups; a logistic regression analysis was used to investigate the risk factors for drug resistance. Results Among the patients with HBV infection in Xuzhou,rtL180 M + rtM204 I/V/S was the most common pattern of drug resistance mutation in the RT region and was observed in 25 patients( 21. 2%),followed by rtA181 T/V in 16 patients( 13. 6%) and rtM204 I/V/S in 15 patients( 12. 7%). Of all 242 patients,13( 5. 4%) had genotype B and 229( 94. 6%) had genotype C,and no other genotypes were found. The patients with genotype B had a significantly higher level of alanine aminotransferase( ALT) than those with genotype C( U =-2. 096,P =0. 036). Compared with the HBeAg-positive group,the HBeAg-negative group had a significantly older age( t = 4. 580,P < 0. 001) and significantly lower HBV DNA load and HBs Ag level( t = 2. 145 and 3. 526,P = 0. 033 and 0. 001). The HBe Ag-negative group had a significantly longer course of disease and a significantly higher level of gamma-glutamyl transpeptidase( GGT) than the HBe Ag-positive group( U =-2. 561 and-2. 016,P = 0. 010 and 0. 044). Compared with the HBe Ag-positive group,the HBe Ag-negative group had a significantly lower proportion of patients with chronic hepatitis B and a significantly higher proportion of patients with liver cirrhosis or hepatocellular carcinoma( χ2= 20. 609,P < 0. 001). The multivariate logistic regression analysis showed that administration of lamivudine + adefovir dipivoxil( OR = 0. 080,95% CI: 0. 008-0. 748,P < 0. 05),administration of adefovir dipivoxil( OR = 5. 493,95% CI: 1. 377-21. 909,P < 0. 05),and improper drug withdrawal( OR = 5. 945,95% CI: 1. 921-18. 403,P < 0. 05) were independent risk factors for drug resistance in patients with HBV infection. Conclusion Most of the patients with HBV infection in Xuzhou are infected with HBV genotype C,with a complex and diverse pattern of drug resistance mutations. HBV DNA replication is active in HBe Ag-positive patients,and therefore,it is recommended to initially select antiviral drugs with high efficiency and low resistance and strengthen the compliance with antiviral therapy.