The Analysis Of P Gene Of Hepatitis B Virus In Chronic Hepatitis B Patients Who Had Viral Breakthrough During Long Term Adefovir Dipivoxil Monotherapy

Background Chronic hepatitis B virus (HBV) infection is a wordwide public health problem. The number of individuals infected with this virus has been estimated to be as high as 350 million. Most of the infectors are from Asia, Africa and Latin America. The prevalence rate of HBsAg is 9.75% in China, and the number of CHB patients is about 30,000,000 to 40,000,000. The key treatment for CHB patients is antiviral treatment. And so far, the antiviral medicine approved can be classified into 2 categories, i.e. interferonαand nucleos(t)ide analogue. Adefovir Dipivoxil (ADV), a nucleotide analogue, demonstrated clinically siginificant antiviral activity against both wild type HBV and lamivudine resistant mutants. However, mutations associated with ADV resistance may developed during long term ADV monotherapy and the liver biochemistry may rebound as a result.Objective To investigate the mutations in P gene of hepatitis B virus in chronic hepatitis B patients who had viral breakthrough during long term adefovir dipivoxil monotherapy.Methods 51 CHB patients who had viral breakthrough (defined as increase in serum HBV DNA by >1log10 above nadir after achieving viral response during continued treatment) during long term adefovir dipivoxil(ADV) monotherapy(10 mg/d, duration >12 months) were included. Sera were collected when viral breakthrough was confirmed, and ALT, HBV DNA(real time quantitative PCR), sequences of partial HBV P gene were determined..Resuls Mutations related to ADV resistance were detected in 37 of 51(72.5%) CHB patients. The frequency of mutation at rt181 was significantly higher than that at rt236 (33 vs 8, P<0.001). The serum HBV DNA load in patients with combination mutation were higher than that with single mutation when the viral breakthrough occurred(6.53±0.451og10 copies/mL vs 5.37±1.081og10 copies/mL, P=0.043), although the ALT levels between groups are comparable(median 57.5 IU/Lvs 70IU/L, P=0.590).Conclusion Mutations in HBV P gene can be developed during ADV monotherapy in CHB patients with the frequency of rtA181V/T higher than that of rtN236T. The HBV DNA levels may differ in patients with different mutations.