scholarly journals Role of the line probe assay INNO-LiPA HBV DR and ultradeep pyrosequencing in detecting resistance mutations to nucleoside/nucleotide analogues in viral samples isolated from chronic hepatitis B patients

2013 ◽  
Vol 94 (12) ◽  
pp. 2729-2738 ◽  
Author(s):  
Sevim Mese ◽  
Muzaffer Arikan ◽  
Aris Cakiris ◽  
Neslihan Abaci ◽  
Ergun Gumus ◽  
...  

Despite the effectiveness of nucleoside/nucleotide analogues in the treatment of chronic hepatitis B (CHB), their long-term administration is associated with the emergence of resistant hepatitis B virus (HBV) mutants. In this study, mutations resulting in antiviral resistance in HBV DNA samples isolated from 23 CHB patients (nine treatment naïve and 14 treated previously) were studied using a line probe assay (INNO-LiPA HBV DR; Innogenetics) and ultradeep pyrosequencing (UDPS) methods. Whilst the INNO-LiPA HBV DR showed no resistance mutations in HBV DNA samples from treatment-naive patients, mutations mediating lamivudine resistance were detected in three samples by UDPS. Among patients who were treated previously, 19 mutations were detected in eight samples using the INNO-LiPA HBV DR and 29 mutations were detected in 12 samples using UDPS. All mutations detected by the INNO-LiPA HBV DR were also detected by UDPS. There were no mutations that could be detected by INNO-LiPA HBV DR but not by UDPS. A total of ten mutations were detected by UDPS but not by INNO-LiPA HBV DR, and the mean frequency of these mutations was 14.7 %. It was concluded that, although INNO-LiPA HBV DR is a sensitive and practical method commonly used for the detection of resistance mutations in HBV infection, UDPS may significantly increase the detection rate of genotypic resistance in HBV at an early stage.

2011 ◽  
Vol 5 (12) ◽  
pp. 882-889 ◽  
Author(s):  
Myo Nyein Aung ◽  
Wattana Leowattana ◽  
Noppadon Tangpukdee ◽  
Chatporn Kittitrakul

Introduction: Hepatitis B virus (HBV) genotype C is prevalent in many areas of the world including Thailand and Southeast Asia. It is a strong risk for hepatocellular carcinoma (HCC) by evidence. We aimed to describe the baseline clinical information of treatment naïve genotype C infected chronic hepatitis B (CHB) patients and to describe the treatment response by surrogate outcome markers in genotype C infected CHB patients after one year of nucleos(t)ide analogues (NA) treatment Methodology:  Thirty-four genotype C CHB patients were studied at the Hospital for Tropical Diseases, Bangkok, including 12 patients treated with lamivudine, 11 with telbivudine, 8 with adefovir, and 3 with entecavir. Serum HBV DNA levels, serum alanine amino transferase ( ALT ) levels, HBeAg status, and alpha-feto protein (AFP) levels were recorded at the start and after twelve months of ongoing treatment. HBV genotyping was performed by line-probe assay. Results: About half of the patients (58.8%) were HBeAg positive. Mean HBV viral load was 6.53 + 1.15 log10 copies per ml at baseline and reduced to 3.63 + 1.3 log10 copies per ml after one year of NA treatment. Serum HBV DNA levels became undetectable in 47.1 % of the patients and serum ALT was normalized in 23.5 % of the patients. Conclusion: Most of the genotype C patients were aged above 40 years. More than half of the genotype C infected patients did not achieve virological response and biochemical remission. Among the CHB patients, genotype C infected patients are a high priority group for intervention.


Diagnostics ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 491
Author(s):  
Thuy Thi Bich Phung ◽  
Son Van Chu ◽  
Son Thien Vu ◽  
Hanh Thi Pham ◽  
Hang Minh Nguyen ◽  
...  

We investigated Nucleos(t)ide-analogue (NA)-resistance mutations (mt) in 142 treatment-naive children with Chronic Hepatitis B (CHB), using a sensitive co-amplification at lower denaturation temperature (COLD)-PCR with Sanger DNA sequencing. An NA resistance-associated mt in the hepatitis B virus (HBV) reverse transcriptase (RT) was found in 66.2% of the patients, with nonclassical mt contributing the most (64.8%). Significantly higher frequencies of Lamivudine (LMV) and Adefovir dipivoxil (ADF) resistance-associated mt were found in genotypes B and C, respectively (ORLMV/ADF: 1495.000; 95% CI: 89.800–24,889.032; p < 0.001). Single-point mt associated to LMV and ADF resistance were detected in 59.9% of the tested children with rtV207M (38.0%) and rtN238T (9.9%) being the most frequent. Multiple-point mt were found only in 8 cases (5.6%): 6 children carried double mt (rtV207M + rtL229V; rtV207M + rtI233V; rtV207I + rtV207M × 2 cases; rtV207M + rtS213T; rtN238A + rtS256G) relating to LMV or/and ADF resistance and 3 children carried triple mt (rtL180M + rtM204I + rtN238T; rtV207M + rtS213T + rtS256G) or quadruple mt (rtL180M + rtM204V + rtV207I/M) for LMV-ADF resistance and Entecavir-reduced susceptibility. Our data indicate that significantly higher frequencies of LMV and ADF-associated mutations were found in treatment-naïve children infected with HBV genotypes B and C, respectively. The developed COLD-PCR method and obtained data may contribute to the development of suitable treatments for children with CHB.


2018 ◽  
Vol 8 ◽  
pp. S22-S23
Author(s):  
Shashank Wanjari ◽  
Vasudha Goel ◽  
Deepak Sharma ◽  
Sudhir Maharshi ◽  
Gaurav Gupta ◽  
...  

2003 ◽  
Vol 114 (1) ◽  
pp. 97-103 ◽  
Author(s):  
Charlotte L. Cameron-Wilson ◽  
Peter Muir ◽  
Anna L. Ballard ◽  
Sally Corden ◽  
Elizabeth H. Boxall ◽  
...  

2016 ◽  
Vol 48 (3) ◽  
pp. 324-327 ◽  
Author(s):  
Lucio Boglione ◽  
Amedeo De Nicolò ◽  
Jessica Cusato ◽  
Gabriele Bonifacio ◽  
Giuseppe Cariti ◽  
...  

2005 ◽  
Vol 17 (5) ◽  
pp. 514-520 ◽  
Author(s):  
R.Y. Sertoz ◽  
S. Erensoy ◽  
S. Pas ◽  
U.S. Akarca ◽  
F. Ozgenc ◽  
...  

2012 ◽  
Vol 1 (4) ◽  
pp. 216-223
Author(s):  
Zhen Ye ◽  
Min Zhao ◽  
He Jiao ◽  
Yang Feng ◽  
Ying-zi Li ◽  
...  

Objective To evaluate the therapeutic effects of telbivudine and entecavir on patients with chronic hepatitis B by meta-analysis method. Methods Databases including the Cochrane Library, PubMed, EMBASE and HighWire were searched from January 2008 to October 2012. Randomized controlled trials on treatment of chronic hepatitis B with telbivudine and entecavir were included. According to the Cochrane systematic reviews, the methodological quality of the included studies was evaluated and effective data was extracted from these studies and analyzed. Results Six studies were included eventually. The telbivudine group included 417 cases and the entecavir group included 396 cases. For 12-week antiviral treatment of chronic hepatitis B, the rate of undetectable HBV DNA was 39.1% with telbivudine and 38.6% with entecavir [OR = 1.04, 95% CI (0.62, 1.73), P > 0.05]; for treatment of HBeAg (+) hepatitis B, the HBeAg clearance rate was 23.8% with telbivudine and 3.8% with entecavir [OR= 8.07, 95% CI (2.69, 24.21), P < 0.05], and the HBeAg seroconversion rate was 6.7% with telbivudine and 3.8% with entecavir [OR = 4.95, 95% CI (1.60, 15.31), P < 0.05]; the ALT normalization rate was 54.3% with telbivudine and 58.5% with entecavir [OR = 0.84, 95% CI (0.49, 1.45), P > 0.05]; and for early-stage treatment, the incidence of adverse events was 17.2% with telbivudine and 22.0% with entecavir [OR = 0.66, 95% CI (0.33, 1.32), P > 0.05]. For 1-year antiviral treatment of chronic hepatitis B, the rate of undetectable HBV DNA was 79.4% with telbivudine and 89.7% with entecavir [OR = 0.46, 95% CI (0.28, 0.74), P < 0.05]; for treatment of HBeAg (+) hepatitis B, the HBeAg clearance rate was 28.9% with telbivudine and 15.6% with entecavir [OR = 2.21, 95% CI (1.06, 4.58), P < 0.05], and the HBeAg seroconversion rate was 31.2% with telbivudine and 18.5% with entecavir [OR = 2.31, 95% CI (1.23, 4.31), P < 0.05]; the ALT normalization rate was 85.8% with telbivudine and 84.9% with entecavir [OR = 0.90, 95% CI (0.29, 2.84), P > 0.05]; and the resistance rate was 6.0% with telbivudine and 0.76% with entecavir [OR = 5.71, 95% CI (1.67, 19.47), P < 0.05]. Conclusions For 1-year treatment of chronic hepatitis B, the difference in ALT normalization between telbivudine and entecavir was not statistically significant; and telbivudine was superior over entecavir in terms of HBeAg undetectable and HBeAg seroconversion; entecavir was superior over telbivudine in terms of HBV DNA undetectable and resistance; and both drugs had similar rates of adverse events in early-stage treatment and no severe adverse event was noted. Both telbivudine and entecavir are effective antiviral drugs against hepatitis B.


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