COLD-PCR Method for Early Detection of Antiviral Drug-Resistance Mutations in Treatment-Naive Children with Chronic Hepatitis B
| Autor: | Son Van Chu, Dung Van Nguyen, Hanh Thi Pham, Ngan Thi Le, Hoan Dang Nguyen, Phuong Thai Truong, Anh Thi Van Nguyen, Son Thien Vu, Van Thi Tuong Vu, Thuy Thi Bich Phung, Hang Minh Nguyen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.drug_class Clinical Biochemistry nucleos(t)ides analogues Biology medicine.disease_cause Article 03 medical and health sciences symbols.namesake 0302 clinical medicine Genotype Adefovir medicine Sanger sequencing Hepatitis B virus COLD-PCR lcsh:R5-920 COLD-PCR method Lamivudine Virology Reverse transcriptase treatment-naive children 030104 developmental biology drug-resistance mutation hepatitis B virus (HBV) symbols 030211 gastroenterology & hepatology Antiviral drug lcsh:Medicine (General) medicine.drug |
| Zdroj: | Diagnostics Volume 10 Issue 7 Diagnostics, Vol 10, Iss 491, p 491 (2020) |
| ISSN: | 2075-4418 |
| Popis: | 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&ndash 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-naï ve 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. |
| Databáze: | OpenAIRE |
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