Clinical Characteristics And Antiviral Effect On Chronic Hepatitis B Patients With Pre-existing RtA181 Mutation

Objective:To objective the detectable rate of hepatitis B virus?HBV?pre-existing rtA181mutation in nucleos?t?ide analogues?NAs?-na?ve Chronic Hepatitis B?CHB?patients,and study the clinical features and antiviral effects of CHB patients with rtA181mutation after NAs treatments.Methods:In this prospective study,all patients received standard antiviral treatments with personal optimized modifications.Common mutations in the reverse transcriptase?RT?domain and HBV genotypes were detected by PCR and Sanger sequencing in every 12 weeks.HBV capture sequencing was performed when samples were confirmed with pre-existing rtA181 mutations.And,HBV DNA and Serological markers of hepatitis B were monitored closely during treatment.Results:1)A total of 233 NAs-untreated patients with CHB were enrolled in this study.71.7%?167/233?and 28.3%?66/233?patients were infected with HBV genotypes B and C,respectively.8 were identified with HBV drug-resistance mutations,including rtA181T?5/233,2.15%?,rtM204V/I?2/233,0.86%?and rtL80V?1/233,0.43%?.2)Among 5 patients with rtA181T mutation,the HBV DNA levels were ranged from 4.82 to 8.26 log₁₀IU/ml,and the HBsAg levels were ranged from 3.03 to 4.34log₁₀IU/ml.All of them were HBeAg positive and infected with HBV genotype C.When compared rtA181T with not-rtA181T mutation groups,there were no significant differences in gender,HBeAg positivity,family history of HBV infection and cirrhosis incidence between these two groups?p>0.05?.However,the frequency of rtA181T mutation in HBV C genotype was higher than that of B genotype?p<0.05?.3)All patients with rtA181T by Sanger sequencing were also rtA181T-positive by HBV capture sequencing.And wild strain always coexist with mutant strain.The percentage of this viral mutation could change after antiviral therapy.4)Among 4 patients with pre-existing rtA181 mutation,2 patients achieved virological response.And HBV DNA was declined gradually in 2 other patients.5)During the antiviral treatment,the HBV strain with rtA181 mutations were observed in 5 patients at month 27,6,27,27 and 21 respectively,including rtA181T+rtN236T,rtA181T,rtA181V,rtA181T,rtA181T.All of them achieved virological response by adding other NAs,or continuing Entecavir?ETV?treatment.6)There was a patient with pre-existing rtA181 mutation diagnosed with hepatocellular carcinoma.While,Liver disease was well controlled in other patients without rtA181T/V,and no disease progression was detected.Conclusions:Pre-existing rtA181T mutation has a certain incidence rate in NA-na?ve CHB patients.We found that the frequency of patients harboring pre-existing rtA181mutation infected with HBV genotype C was higher than genotype B.However,a further research is needed to investigate the long-term antiviral effect in patients with rtA181 mutation and specific relationship between this mutation and the deterioration of liver disease.