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J Viral Hepat. 2011 Apr;18(4):e29-39. doi: 10.1111/j.1365-2893.2010.01360.x.
Epub 2010 Sep 6.
Genotypic resistance profile of hepatitis B virus (HBV) in a large cohort of
nucleos(t)ide analogue-experienced Chinese patients with chronic HBV infection.
Liu Y, Wang C, Zhong Y, Li X, Dai J, Ren X, Xu Z, Li L, Yao Z, Ji D, Wang L,
Zhang L, Wong VW, Zoulim F, Xu D. Viral Hepatitis Research Laboratory, Institute
of Infectious Diseases, Beijing 302 Hospital, Beijing, China Department of
Medicine and Therapeutics and Institute of Digestive Disease, The Chinese
University of Hong Kong, Hong Kong, China INSERM, U871, Lyon, France Université
Lyon 1, IFR62 Lyon-Est, Lyon, France Hospices Civils de Lyon, Hôtel Dieu,
Department of Hepatology and Gastroenterology, Lyon, France.
Abstract
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.
© 2010 Blackwell Publishing Ltd.
PMID: 21392168 [PubMed - in process] |
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发表于 2011-3-22 13:29
