Published online Dec 7, 2014. doi: 10.3748/wjg.v20.i45.17100
Revised: July 17, 2014
Accepted: August 13, 2014
Published online: December 7, 2014
Processing time: 196 Days and 5.8 Hours
AIM: To investigate the loci of adefovir dipivoxil (ADV)-induced resistance in hepatitis B virus (HBV) isolates and optimize the management of ADV-treated patients.
METHODS: Between June 2008 and August 2010, a cross-sectional control study was conducted comprising 79 patients with chronic HBV infection-related liver disease who had been administered ADV monotherapy. Patients underwent liver imaging. Serum DNA extracts were analyzed for HBV DNA levels, genotypes, and serology markers, and deep sequencing of the HBV P gene was performed.
RESULTS: ADV-resistant patients were found either with a single mutated locus, or with coexisting mutated loci. The most prevalent mutations were rtA181T, rtV214A, and rtN236T. Twenty-six patients had more than two mutated loci. The mutants were distributed among the patients without any significant affinity for gender, age, end-stage of liver disease, complications of non-alcoholic fatty liver disease, or HBV DNA levels. Patients with the rtA181T mutant were primarily infected with genotype C and e-antigen negative HBV, while patients with the rtN236T mutant were primarily infected by genotype B HBV (χ2 = 6.004, 7.159; P = 0.023, 0.007). The duration of treatment with ADV was shorter in the single mutant group compared with the multi-mutant group (t = 2.426, P = 0.018).
CONCLUSION: Drug-resistant HBV mutants are complex and diverse. Patients should receive the standard and first-line antiviral treatment, strictly comply with medication dosage, and avoid short-term withdrawal.
Core tip: Currently, hepatitis B virus (HBV) resistance to adefovir dipivoxil (ADV) has become more prevalent. However, it is not known whether drug-resistant HBV mutants induced by ADV are related to the clinical features of patients. In this study, we analyzed the exhaustive resistant mutants induced by ADV. Of 79 patients, 26 (32.9%) had more than two loci of drug resistance in HBV mutants. Because drug-resistant HBV mutants induced by ADV are complicated and diverse, we conclude that testing for resistant mutants prior to antiviral treatment, administering standard and first-line antiviral treatment, and personalizing medication according to the clinical characteristics of patients is important to avoid subsequent noncompliance and the need for salvage treatment.