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, Yanwei; Li, X.; Dai, Jiu-zeng; Xiaoqiang, Ren; Xu, Zhihui; Li, L.; Yao, Zilong; Ji, Dong; Wang, L.; Zhang, L.; Wong, Vincent Wai‐Sun; Zoulim, Fabien; Xu, Da

doi:10.1111/j.1365-2893.2010.01360.x

Cited by 55 publications

(53 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with previous studies [14,17], the incidence of the rtM204V/I mutation was highest (34.53%; 48/139) in CHB patients who had received NAs; this mutation was associated with resistance to LAM, LdT, and ETV. RtM204V/I was the major mutation type (48/58; 87.1%) in the patients who were found to harbor drug resistance mutations.…”

Section: Discussionsupporting

confidence: 79%

“…The prevalence of genotypic resistance mutations was 41.72% (58/139), which is different from the prevalence reported in other countries [20][21][22][23], and is also different from studies in other regions of China [14,17,24]. The discrepancy might be due to race and genotype of HBV in different countries, because the predominant HBV genotypes in Europe are A and D. However, the dominating HBV genotype in Korea is C. In China, though genotypes B and C are major genotypes, reports of the distribution of the genotypes in different region are inconsistent [19], which may also affect the frequency of genotypic resistance mutations.…”

Section: Discussioncontrasting

confidence: 51%

“…The entire RT region (nt54-1278) of HBV was amplified using nested PCR as previously described [17]. The sequence of the PCR primers is shown in Table 1.…”

Section: Amplification Of the Rt Region In The Hbv Genomementioning

confidence: 99%

See 2 more Smart Citations

Monitoring of genotypic resistance profile in chronic hepatitis B patients receiving nucleos(t)ide analogues in Huzhou, China

Qian

Qin

et al. 2016

J Infect Dev Ctries

View full text Add to dashboard Cite

Introduction: Antiviral drug-resistance patterns of hepatitis B virus (HBV) mutants are complex and currently partly understood. The aim of this study was to monitor the genotypic resistance profile in patients with chronic hepatitis B (CHB) receiving nucleos(t)ide analogues (NAs) in Huzhou, eastern China. Methodology: Serum samples of 139 CHB patients undergoing NA treatment were obtained from Huzhou Central Hospital. The full-length HBV reverse transcriptase regions were amplified and sequenced. The NA resistance mutation positions, including rtL80, rtI169, rtV173, rtL180, rtA181, rtT184, rtA194, rtS202, rtM204, rtI233, rtN236, and rtM250 were analyzed. Results: Genotypic resistance mutations were detected in 41.72% (58/139) of patients with CHB. Drug resistance mutations were detected at positions rt80, rt173, rt180, rt181, rt194, rt202, rt204, rt236, and rt250, but were not observed at positions rt169, rt184, and rt233. The prevalence of mutations at rtM204 was 54.44% in 90 patients who were treated with lamivudine (LAM) or telbivudine (LDT). RtN236 mutations were detected in 7.14% (2/28) of the patients receiving adefovir (ADV) therapy. Additionally, rtA181 mutations were observed in 4 patients with LAM, ADV, and LDT-based therapy, but not in those patients treated with entecavir (ETV). Among patients who harbored rtM204 combination mutations, rtM204I and rtM204V were significantly associated with rtL80I/V and rtL180M, respectively. Conclusions: The mutation patterns of NA-resistant HBV are complicated in CHB patients in the current clinical setting. Thus, it is necessary to persistently monitor the resistance mutations of HBV for optimizing antiviral therapy strategy and for preventing an outbreak of clinical resistance.

show abstract

Section: Discussionsupporting

confidence: 79%

Section: Discussioncontrasting

confidence: 51%

See 1 more Smart Citation

Monitoring of genotypic resistance profile in chronic hepatitis B patients receiving nucleos(t)ide analogues in Huzhou, China

Qian

Qin

et al. 2016

J Infect Dev Ctries

View full text Add to dashboard Cite

show abstract

“…All patients were anti-HCV-and anti-HIV-negative (45 male patients and 20 female patients, mean age 8·6 Ϯ 4·7 years, range 1-18 years). The diagnostic criteria were based on the Management Scheme of Diagnostic and Therapy Criteria of Viral Hepatitis, issued by the Chinese Society of Infectious Diseases and Parasitology and the Chinese Society of Hepatology, which have been described in detail in our previous studies [21,22]. The inclusion criteria were: all patients who were serum hepatitis B surface antigen (HBsAg)-positive for at least 6 months, but there was no evidence for hepatocellular carcinoma (HCC), or concomitant of HCV, HDV, HIV infection and autoimmune liver disease.…”

Section: Methodsmentioning

confidence: 99%

The correlation between T helper type 17 cells and clinical characters in Chinese paediatric patients with chronic hepatitis B

Zhu

Zhang

et al. 2013

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SummaryInterleukin (IL)-17-mediated immune response has been shown to play a critical role in inflammation-associated disease. However, its role in the pathogenesis of chronic hepatitis B virus (HBV) in paediatric patients remains unknown. We investigated the frequency of T helper type 17 (Th17) cells and evaluated the association between the Th17 and clinical characters in paediatric patients with chronic hepatitis B (CHB). The frequency of Th17 cells was detected by flow cytometry analyses from 65 paediatric patients with CHB and nine healthy controls. The degree of hepatic inflammation was graded using the histological activity index (HAI). Compared with healthy controls, the frequency of Th17 cells in peripheral blood was significantly higher in paediatric patients with CHB. The proportion of Th17 cells was higher in the patients with higher HAI score (G2-G3) compared to those subjects with lower HAI score (G0-G1), but the frequency of Th17 cells had no correlation with serum HBV DNA loads or alanine aminotransferase levels. Compared with the younger age group (age 1-6 years), Th17 cell frequency was higher in the older age group (age 7-18 years). Peripheral Th17 cell frequency is associated closely with inflammation activity of liver tissues in paediatric patients with CHB.

show abstract

“…A clonal analysis of the reverse transcriptase fragment of the HBV P gene was performed as previously reported after the MLP-RT-PCR assay (20). In brief, the reverse transcriptase fragment of the HBV P gene was amplified by general PCR as described in "DNA extraction and PCR amplification before detection," above.…”

Section: Clonal Sequencingmentioning

confidence: 99%

Rapid Detection of Hepatitis B Virus Variants Associated with Lamivudine and Adefovir Resistance by Multiplex Ligation-Dependent Probe Amplification Combined with Real-Time PCR

Jia

Wang

et al. 2014

J Clin Microbiol

View full text Add to dashboard Cite

C hronic hepatitis B virus (HBV) infection remains a major public health problem worldwide. Two drugs, lamivudine (LAM) and adefovir (ADV), are presently used as first-line therapies against HBV in China. Antiviral drug resistance is the major obstacle to successful long-term therapy for chronic hepatitis B infection (1, 2). The detection of mutations associated with resistance to LAM and ADV is very important for the clinical selection of drugs used against HBV. At present, there are many methods to detect drug-resistant mutations of HBV, including direct sequencing from PCR products, reverse hybridization INNO-LiPA, microarray, and real-time PCR. Direct sequencing and INNOLiPA are well-known methods used in clinical practice. Although direct sequencing is the gold standard for the detection of mutations, it cannot detect mutations that are present at a low frequency (Ͻ20%) in the viral population (3). The INNO-LiPA (4, 5) is more sensitive, but the reagents and equipment are costly. Microarray is high-throughput but is also costly; therefore, a microarray cannot be widely used in clinical practice (6). With the development of new technologies in molecular diagnostics, realtime PCR was applied to detect HBV mutations. For many realtime PCRs, the mutants and wild-type strains were distinguished by changes in the melting temperatures (T m ) of the fluorescence probes (7), which result in a low rate of identification of mutations with similar T m values, adjacent mutations, and silent mutations. Moreover, the mutation sites need to be located in the middle of the fluorescence probes, such as in a type-specific minor groove binder probe (8-10) or a locked nucleic acid probe (11), thus restricting the design of probes and the detection flux. In most cases, only single-codon mutations can be detected by traditional real-time PCR. We have developed a new detection method, multiplex ligation-dependent real-time PCR (MLP-RT-PCR), which combines multiplex ligation-dependent probe amplification (MLPA) with real-time PCR. The method can be applied to quickly detect five HBV mutations associated with resistance to LAM and ADV in one tube, including the mutations rtM204V/I, rtA181V/T, and rtN236T in the reverse transcriptase domain of the HBV P gene (12)(13)(14). Schouten et al. (15) reported on the first MLPA assay in 2002. Forty pairs of MLPA probes were designed to detect changes in gene copies. The assay can also be used to detect single nucleotide polymorphism (SNPs) and point mutations (16), and it has been applied for detecting multiple-drug-resistant mutations and genotyping in Mycobacterium tuberculosis (17,18). In the traditional MLPA, pathogens are quantified and genotyped by capillary electrophoresis (18) or microarray (17). The synthesis of many different lengths of MLPA probes or complex operations, such as the fixation of probes, hybridization, and elution, are needed. However, using a TaqMan probe inserted into the MLPA probe as a tag, the MLPA probe can be directly amplified by realtime PCR and the results ...

show 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

Cited by 55 publications

References 51 publications

Monitoring of genotypic resistance profile in chronic hepatitis B patients receiving nucleos(t)ide analogues in Huzhou, China

Monitoring of genotypic resistance profile in chronic hepatitis B patients receiving nucleos(t)ide analogues in Huzhou, China

The correlation between T helper type 17 cells and clinical characters in Chinese paediatric patients with chronic hepatitis B

Rapid Detection of Hepatitis B Virus Variants Associated with Lamivudine and Adefovir Resistance by Multiplex Ligation-Dependent Probe Amplification Combined with Real-Time PCR

Contact Info

Product

Resources

About