Genotypic resistance profile of hepatitis B virus (HBV) in a large cohort of nucleos(t)ide analogue-experienced Chinese patients with chronic HBV infection

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2893.2010.01360.x/abstract

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

Article first published online: 6 SEP 2010

DOI: 10.1111/j.1365-2893.2010.01360.x

© 2010 Blackwell Publishing Ltd

Issue

Journal of Viral Hepatitis

Volume 18, Issue 4, pages e29–e39, April 2011

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.

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2893.2010.01360.x/abstract

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

Article first published online: 6 SEP 2010

DOI: 10.1111/j.1365-2893.2010.01360.x

© 2010 Blackwell Publishing Ltd

Issue

Journal of Viral Hepatitis

Volume 18, Issue 4, pages e29–e39, April 2011

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.