Genotypic resistance profile of hepatitis B virus (HBV) in a large cohort of
nucleos(t)ide analogue-experienced Chinese patients with chronic HBV infection
Y. Liu1, C. Wang1, Y. Zhong1, X. Li1, J. Dai1, X. Ren1, Z. Xu1, L. Li1, Z. Yao1,
D. Ji1, L. Wang1, L. Zhang1, V. W. -S. Wong2, F. Zoulim3,4,5, D. Xu1
Summary. The study investigated the hepatitis B virus (HBV) genotypic
resistance profile in 1803 nucleos(t)ide analogue (NA)-experienced Chinese
patients with chronic HBV infection. Serum HBV DNA was extracted, and the
reverse transcriptase region was analysed by a high-sensitive direct PCR
sequencing and verified by clonal sequencing if necessary. Drug-resistant
mutations were detected in 560 of the 1803 patients, including 214 of 490
patients who received lamivudine (LAM), 35 of 428 patients who received adefovir
(ADV), five of 18 patients who received telbivudine and 306 of 794 patients who
received various sequential/combined NA therapies. ADV-resistant mutations were
detected in 36 of 381 patients who received LAM and then switched-to ADV in
contrast to one of 82 patients who received ADV add-on LAM. Entecavir
(ETV)-resistant mutations were detected not only in LAM- and ETV-treated
patients but also in LAM-treated ETV-naïve patients. Double mutations rtM204I
and rtL180M were detected more frequently in genotype C than in genotype B
virus, and patients infected with this mutant had higher alanine transaminase
levels than those infected with mutant containing the rtM204I substitution
alone. Multidrug-resistant HBV strains were identified in eight patients,
including two novel strains with mutational patterns rtL180M + A181V + S202G +
M204V + N236T and rtL180M + S202G + M204V + N236T. The results provide new
information on HBV genotypic resistance profiles in a large cohort of Chinese
patients with chronic HBV infection and may have important clinical implication
for HBV drug resistance management in China.