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Emergence of the rtA181T/sW172* mutant increased the risk of hepatoma occurrence in patients with lamivudine-resistant chronic hepatitis B
BACKGROUND: Development of the hepatitis B virus (HBV) rtA181T/sW172* mutant could occur during prolonged lamivudine (LAM) therapy, conferring cross resistance to adefovir. Recent studies demonstrated an increased oncogenic potential of this mutant in NIH3T3 cells. In this study, we aimed to investi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3184121/ https://www.ncbi.nlm.nih.gov/pubmed/21933446 http://dx.doi.org/10.1186/1471-2407-11-398 |
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author | Yeh, Chau-Ting Chen, Tiffany Hsu, Chao-Wei Chen, Yi-Cheng Lai, Ming-Wei Liang, Kung-Hao Chen, Tse-Ching |
author_facet | Yeh, Chau-Ting Chen, Tiffany Hsu, Chao-Wei Chen, Yi-Cheng Lai, Ming-Wei Liang, Kung-Hao Chen, Tse-Ching |
author_sort | Yeh, Chau-Ting |
collection | PubMed |
description | BACKGROUND: Development of the hepatitis B virus (HBV) rtA181T/sW172* mutant could occur during prolonged lamivudine (LAM) therapy, conferring cross resistance to adefovir. Recent studies demonstrated an increased oncogenic potential of this mutant in NIH3T3 cells. In this study, we aimed to investigate the clinical significance of this finding. METHODS: Serum samples from 123 LAM-resistant chronic hepatitis B patients were submitted for virological assays. A highly sensitive amplification created restriction enzyme site (ACRES) method was devised to detect small amounts of the rtA181T mutant in the serum. Virological factors including HBV-DNA level, genotype, precore G1896A, BCP A1762T/G1764A, rtM204I/V, rtA181T and pre-S internal deletion mutations as well as clinical variables including subsequent use of rescue drugs were submitted for outcome analysis. RESULTS: By use of the highly sensitive ACRES method, the rtA181T mutant was detectable in 10 of the 123 LAM-resistant patients. During the mean follow-up period of 26.2 ± 16.4 months (range 2 to 108 months), 3 of the 10 (30.0%) rtA181T-positive patients and 2 of the 113 (1.8%) rtA181T-negative patients developed hepatocellular carcinoma (HCC). Kaplan-Meier analysis indicated that the presence of rtA181T mutation (P < 0.001), age > 50 years (P = 0.001), and liver cirrhosis (P < 0.001) were significantly associated with subsequent occurrence of HCC. All 5 HCC patients belonged to the older age and cirrhosis groups. CONCLUSIONS: Emergence of the rtA181T/sW172* mutant in LAM-resistant patients increased the risk of HCC development in the subsequent courses of antiviral therapy. |
format | Online Article Text |
id | pubmed-3184121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-31841212011-10-01 Emergence of the rtA181T/sW172* mutant increased the risk of hepatoma occurrence in patients with lamivudine-resistant chronic hepatitis B Yeh, Chau-Ting Chen, Tiffany Hsu, Chao-Wei Chen, Yi-Cheng Lai, Ming-Wei Liang, Kung-Hao Chen, Tse-Ching BMC Cancer Research Article BACKGROUND: Development of the hepatitis B virus (HBV) rtA181T/sW172* mutant could occur during prolonged lamivudine (LAM) therapy, conferring cross resistance to adefovir. Recent studies demonstrated an increased oncogenic potential of this mutant in NIH3T3 cells. In this study, we aimed to investigate the clinical significance of this finding. METHODS: Serum samples from 123 LAM-resistant chronic hepatitis B patients were submitted for virological assays. A highly sensitive amplification created restriction enzyme site (ACRES) method was devised to detect small amounts of the rtA181T mutant in the serum. Virological factors including HBV-DNA level, genotype, precore G1896A, BCP A1762T/G1764A, rtM204I/V, rtA181T and pre-S internal deletion mutations as well as clinical variables including subsequent use of rescue drugs were submitted for outcome analysis. RESULTS: By use of the highly sensitive ACRES method, the rtA181T mutant was detectable in 10 of the 123 LAM-resistant patients. During the mean follow-up period of 26.2 ± 16.4 months (range 2 to 108 months), 3 of the 10 (30.0%) rtA181T-positive patients and 2 of the 113 (1.8%) rtA181T-negative patients developed hepatocellular carcinoma (HCC). Kaplan-Meier analysis indicated that the presence of rtA181T mutation (P < 0.001), age > 50 years (P = 0.001), and liver cirrhosis (P < 0.001) were significantly associated with subsequent occurrence of HCC. All 5 HCC patients belonged to the older age and cirrhosis groups. CONCLUSIONS: Emergence of the rtA181T/sW172* mutant in LAM-resistant patients increased the risk of HCC development in the subsequent courses of antiviral therapy. BioMed Central 2011-09-21 /pmc/articles/PMC3184121/ /pubmed/21933446 http://dx.doi.org/10.1186/1471-2407-11-398 Text en Copyright ©2011 Yeh et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Yeh, Chau-Ting Chen, Tiffany Hsu, Chao-Wei Chen, Yi-Cheng Lai, Ming-Wei Liang, Kung-Hao Chen, Tse-Ching Emergence of the rtA181T/sW172* mutant increased the risk of hepatoma occurrence in patients with lamivudine-resistant chronic hepatitis B |
title | Emergence of the rtA181T/sW172* mutant increased the risk of hepatoma occurrence in patients with lamivudine-resistant chronic hepatitis B |
title_full | Emergence of the rtA181T/sW172* mutant increased the risk of hepatoma occurrence in patients with lamivudine-resistant chronic hepatitis B |
title_fullStr | Emergence of the rtA181T/sW172* mutant increased the risk of hepatoma occurrence in patients with lamivudine-resistant chronic hepatitis B |
title_full_unstemmed | Emergence of the rtA181T/sW172* mutant increased the risk of hepatoma occurrence in patients with lamivudine-resistant chronic hepatitis B |
title_short | Emergence of the rtA181T/sW172* mutant increased the risk of hepatoma occurrence in patients with lamivudine-resistant chronic hepatitis B |
title_sort | emergence of the rta181t/sw172* mutant increased the risk of hepatoma occurrence in patients with lamivudine-resistant chronic hepatitis b |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3184121/ https://www.ncbi.nlm.nih.gov/pubmed/21933446 http://dx.doi.org/10.1186/1471-2407-11-398 |
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