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James Fung - One of the best experts on this subject based on the ideXlab platform.
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effects of Nucleoside Analogue prescription for hepatitis b on the incidence of liver cancer in hong kong a territory wide ecological study
Alimentary Pharmacology & Therapeutics, 2017Co-Authors: W K Seto, Eric H Y Lau, Ivan Hung, W K Leung, Ka Shing Cheung, James Fung, Chinglung Lai, M F YuenAbstract:SummaryBackground The temporal relationship between Nucleoside Analogue therapy for chronic hepatitis B (CHB) and liver cancer development has not been evaluated at a population level. Aim To investigate the impact of Nucleoside Analogue prescription on liver cancer incidence in a CHB-prevalent region. Methods We obtained territory-wide Nucleoside Analogue prescription data from 1999, when Nucleoside Analogue was first available in Hong Kong, to 2012 and the population-based liver cancer incidence data from 1990 to 2012. We compared the liver cancer incidences from 1990 to 1998 and 1999 to 2012 with adjustment for local hepatitis B surface antigen seroprevalence. Results Nucleoside Analogue prescription patient headcount increased from 2006 per year in 1999 to 26 411 in 2012. Prescription volume in 2012 was highest among 55–64 years (30.3%), higher than 65–74 years (13.0%) and ≥75 years (5.8%). Age-standardised liver cancer incidence 1999–2012 decreased by 1.88%/year (95% CI 3.34% to 0.42%/year). NA therapy was associated with decline in age-adjusted liver cancer incidence (2.7 per 100 000 persons, P 0.05). Conclusions Nucleoside Analogue prescription was associated with a reduction of overall liver cancer incidence in a CHB-prevalent region. The lack of association among individuals of ≥65 years was consistent with the low Nucleoside Analogue prescription volume in elderly patients, mitigating the impact of CHB treatment on liver cancer.
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body mass index is associated with fibrosis regression during long term Nucleoside Analogue therapy in chronic hepatitis b
Alimentary Pharmacology & Therapeutics, 2016Co-Authors: W K Seto, Ka Shing Cheung, James Fung, Chinglung Lai, Lungyi Mak, R W Hui, K S H Liu, M F YuenAbstract:SummaryBackground Factors influencing changes in liver stiffness measurements during long-term Nucleoside Analogue therapy for chronic hepatitis B (CHB) have not been thoroughly investigated. Aim To identify determinants of on-treatment fibrosis regression in CHB. Methods We performed follow-up liver stiffness and controlled attenuation parameter measurements on Nucleoside Analogue-treated CHB patients with severe liver fibrosis, according to EASL-ALEH criteria, diagnosed by transient elastography in 2006–2008. Anthropometric measurements and different metabolic parameters were recorded. Results Among 257 patients with severe liver fibrosis by initial transient elastography, 123 (47.9%) were recruited for reassessment. Median treatment duration was 87.5 (interquartile range 75.3–102.2) months; 97.5% had undetectable HBV DNA. There was a significant reduction in median liver stiffness from 14.6 to 8.3 kPa (P 0.05). Conclusion An increased BMI hindered fibrosis regression in patients with chronic hepatitis B during Nucleoside Analogue treatment, suggesting that control of metabolic risk factors, in addition to virologic suppression via antiviral therapy, might be needed to halt the fibrogenic process in chronic hepatitis B.
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hepatitis b surface antigen seroclearance during Nucleoside Analogue therapy surface antigen kinetics outcomes and durability
Journal of Gastroenterology, 2016Co-Authors: Waikay Seto, Ka Shing Cheung, James Fung, Chinglung Lai, Danny Kaho Wong, Fungyu Huang, Kevin Szehang Liu, Manfung YuenAbstract:Background Hepatitis B surface antigen (HBsAg) seroclearance is the recommended treatment end point for Nucleoside Analogue (NA) therapy in chronic hepatitis B, yet the underlying kinetics and durability of HBsAg seroclearance in NA-treated patients have not been well described.
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reduction of hepatitis b surface antigen levels and hepatitis b surface antigen seroclearance in chronic hepatitis b patients receiving 10 years of Nucleoside Analogue therapy
Hepatology, 2013Co-Authors: Waikay Seto, James Fung, Chinglung Lai, Danny Kaho Wong, Fungyu Huang, Manfung YuenAbstract:The profile and clinical significance of serum hepatitis B surface antigen (HBsAg) levels during long-term Nucleoside Analogue (NA) therapy in chronic hepatitis B (CHB) is undetermined. From 1994 to 2002, 322 Chinese CHB patients were started on lamivudine in our center. Patients were recruited if they were continuously treated with lamivudine for at least 10 years and maintained favorable virologic responses throughout therapy (HBV DNA 0.05). Seven (10%) patients achieved HBsAg seroclearance, and when compared with the remaining 63 patients, had significantly lower median baseline HBsAg levels (P = 0.012) and a greater median rate of HBsAg reduction (P 0.166 log IU/mL/year were optimal cutoff levels in predicting subsequent HBsAg seroclearance (negative predictive values, 98.1% and 97.8%, respectively). Conclusion: Low baseline HBsAg levels and greater rate of HBsAg reduction achieved high predictive values for predicting HBsAg seroclearance, strengthening the prognostic role of HBsAg measurements during NA therapy. (Hepatology 2013;53:923–931)
Chinglung Lai - One of the best experts on this subject based on the ideXlab platform.
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effects of Nucleoside Analogue prescription for hepatitis b on the incidence of liver cancer in hong kong a territory wide ecological study
Alimentary Pharmacology & Therapeutics, 2017Co-Authors: W K Seto, Eric H Y Lau, Ivan Hung, W K Leung, Ka Shing Cheung, James Fung, Chinglung Lai, M F YuenAbstract:SummaryBackground The temporal relationship between Nucleoside Analogue therapy for chronic hepatitis B (CHB) and liver cancer development has not been evaluated at a population level. Aim To investigate the impact of Nucleoside Analogue prescription on liver cancer incidence in a CHB-prevalent region. Methods We obtained territory-wide Nucleoside Analogue prescription data from 1999, when Nucleoside Analogue was first available in Hong Kong, to 2012 and the population-based liver cancer incidence data from 1990 to 2012. We compared the liver cancer incidences from 1990 to 1998 and 1999 to 2012 with adjustment for local hepatitis B surface antigen seroprevalence. Results Nucleoside Analogue prescription patient headcount increased from 2006 per year in 1999 to 26 411 in 2012. Prescription volume in 2012 was highest among 55–64 years (30.3%), higher than 65–74 years (13.0%) and ≥75 years (5.8%). Age-standardised liver cancer incidence 1999–2012 decreased by 1.88%/year (95% CI 3.34% to 0.42%/year). NA therapy was associated with decline in age-adjusted liver cancer incidence (2.7 per 100 000 persons, P 0.05). Conclusions Nucleoside Analogue prescription was associated with a reduction of overall liver cancer incidence in a CHB-prevalent region. The lack of association among individuals of ≥65 years was consistent with the low Nucleoside Analogue prescription volume in elderly patients, mitigating the impact of CHB treatment on liver cancer.
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body mass index is associated with fibrosis regression during long term Nucleoside Analogue therapy in chronic hepatitis b
Alimentary Pharmacology & Therapeutics, 2016Co-Authors: W K Seto, Ka Shing Cheung, James Fung, Chinglung Lai, Lungyi Mak, R W Hui, K S H Liu, M F YuenAbstract:SummaryBackground Factors influencing changes in liver stiffness measurements during long-term Nucleoside Analogue therapy for chronic hepatitis B (CHB) have not been thoroughly investigated. Aim To identify determinants of on-treatment fibrosis regression in CHB. Methods We performed follow-up liver stiffness and controlled attenuation parameter measurements on Nucleoside Analogue-treated CHB patients with severe liver fibrosis, according to EASL-ALEH criteria, diagnosed by transient elastography in 2006–2008. Anthropometric measurements and different metabolic parameters were recorded. Results Among 257 patients with severe liver fibrosis by initial transient elastography, 123 (47.9%) were recruited for reassessment. Median treatment duration was 87.5 (interquartile range 75.3–102.2) months; 97.5% had undetectable HBV DNA. There was a significant reduction in median liver stiffness from 14.6 to 8.3 kPa (P 0.05). Conclusion An increased BMI hindered fibrosis regression in patients with chronic hepatitis B during Nucleoside Analogue treatment, suggesting that control of metabolic risk factors, in addition to virologic suppression via antiviral therapy, might be needed to halt the fibrogenic process in chronic hepatitis B.
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hepatitis b surface antigen seroclearance during Nucleoside Analogue therapy surface antigen kinetics outcomes and durability
Journal of Gastroenterology, 2016Co-Authors: Waikay Seto, Ka Shing Cheung, James Fung, Chinglung Lai, Danny Kaho Wong, Fungyu Huang, Kevin Szehang Liu, Manfung YuenAbstract:Background Hepatitis B surface antigen (HBsAg) seroclearance is the recommended treatment end point for Nucleoside Analogue (NA) therapy in chronic hepatitis B, yet the underlying kinetics and durability of HBsAg seroclearance in NA-treated patients have not been well described.
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reduction of hepatitis b surface antigen levels and hepatitis b surface antigen seroclearance in chronic hepatitis b patients receiving 10 years of Nucleoside Analogue therapy
Hepatology, 2013Co-Authors: Waikay Seto, James Fung, Chinglung Lai, Danny Kaho Wong, Fungyu Huang, Manfung YuenAbstract:The profile and clinical significance of serum hepatitis B surface antigen (HBsAg) levels during long-term Nucleoside Analogue (NA) therapy in chronic hepatitis B (CHB) is undetermined. From 1994 to 2002, 322 Chinese CHB patients were started on lamivudine in our center. Patients were recruited if they were continuously treated with lamivudine for at least 10 years and maintained favorable virologic responses throughout therapy (HBV DNA 0.05). Seven (10%) patients achieved HBsAg seroclearance, and when compared with the remaining 63 patients, had significantly lower median baseline HBsAg levels (P = 0.012) and a greater median rate of HBsAg reduction (P 0.166 log IU/mL/year were optimal cutoff levels in predicting subsequent HBsAg seroclearance (negative predictive values, 98.1% and 97.8%, respectively). Conclusion: Low baseline HBsAg levels and greater rate of HBsAg reduction achieved high predictive values for predicting HBsAg seroclearance, strengthening the prognostic role of HBsAg measurements during NA therapy. (Hepatology 2013;53:923–931)
Manfung Yuen - One of the best experts on this subject based on the ideXlab platform.
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hepatitis b surface antigen seroclearance during Nucleoside Analogue therapy surface antigen kinetics outcomes and durability
Journal of Gastroenterology, 2016Co-Authors: Waikay Seto, Ka Shing Cheung, James Fung, Chinglung Lai, Danny Kaho Wong, Fungyu Huang, Kevin Szehang Liu, Manfung YuenAbstract:Background Hepatitis B surface antigen (HBsAg) seroclearance is the recommended treatment end point for Nucleoside Analogue (NA) therapy in chronic hepatitis B, yet the underlying kinetics and durability of HBsAg seroclearance in NA-treated patients have not been well described.
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reduction of hepatitis b surface antigen levels and hepatitis b surface antigen seroclearance in chronic hepatitis b patients receiving 10 years of Nucleoside Analogue therapy
Hepatology, 2013Co-Authors: Waikay Seto, James Fung, Chinglung Lai, Danny Kaho Wong, Fungyu Huang, Manfung YuenAbstract:The profile and clinical significance of serum hepatitis B surface antigen (HBsAg) levels during long-term Nucleoside Analogue (NA) therapy in chronic hepatitis B (CHB) is undetermined. From 1994 to 2002, 322 Chinese CHB patients were started on lamivudine in our center. Patients were recruited if they were continuously treated with lamivudine for at least 10 years and maintained favorable virologic responses throughout therapy (HBV DNA 0.05). Seven (10%) patients achieved HBsAg seroclearance, and when compared with the remaining 63 patients, had significantly lower median baseline HBsAg levels (P = 0.012) and a greater median rate of HBsAg reduction (P 0.166 log IU/mL/year were optimal cutoff levels in predicting subsequent HBsAg seroclearance (negative predictive values, 98.1% and 97.8%, respectively). Conclusion: Low baseline HBsAg levels and greater rate of HBsAg reduction achieved high predictive values for predicting HBsAg seroclearance, strengthening the prognostic role of HBsAg measurements during NA therapy. (Hepatology 2013;53:923–931)
Kazunari Taira - One of the best experts on this subject based on the ideXlab platform.
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specific 3 terminal modification of dna with a novel Nucleoside Analogue that allows a covalent linkage of a nuclear localization signal and enhancement of dna stability
ChemBioChem, 2005Co-Authors: Yutaka Ikeda, Shunichi Kawahara, Koichi Yoshinari, Satoshi Fujita, Kazunari TairaAbstract:: We report a straightforward method for the site-specific modification of long double-stranded DNA by using a maleimide adduct of deoxycytidine. This novel Nucleoside Analogue was efficiently incorporated at the 3'-termini of DNA by terminal deoxynucleotidyl transferase (TdT). Thiol-containing compounds can be covalently linked to the maleimide moieties. We added a nuclear localization signal peptide to the 3'-terminal of a 350 bp-long DNA that encoded short-hairpin RNA, and these modifications resulted in the enhancement of silencing activity by RNA interference. This enhancement is mainly attributed to increased stability of the template DNA.
Jean A Bernatchez - One of the best experts on this subject based on the ideXlab platform.
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activity of selected Nucleoside Analogue protides against zika virus in human neural stem cells
Viruses, 2019Co-Authors: Jean A Bernatchez, Michael Coste, Sungjun Beck, Grace Wells, Lucas A Luna, Alex E Clark, Zhe Zhu, David HechtAbstract:Zika virus (ZIKV), an emerging flavivirus that causes neurodevelopmental impairment to fetuses and has been linked to Guillain-Barre syndrome continues to threaten global health due to the absence of targeted prophylaxis or treatment. Nucleoside Analogues are good examples of efficient anti-viral inhibitors, and prodrug strategies using phosphate masking groups (ProTides) have been employed to improve the bioavailability of riboNucleoside Analogues. Here, we synthesized and tested a small library of 13 ProTides against ZIKV in human neural stem cells. Strong activity was observed for 2′-C-methyluridine and 2′-C-ethynyluridine ProTides with an aryloxyl phosphoramidate masking group. Substitution of a 2-(methylthio) ethyl phosphoramidate for the aryloxyl phosphoramidate ProTide group of 2′-C-methyluridine completely abolished antiviral activity of the compound. The aryloxyl phosphoramidate ProTide of 2′-C-methyluridine outperformed the hepatitis C virus (HCV) drug sofosbuvir in suppression of viral titers and protection from cytopathic effect, while the former compound’s triphosphate active metabolite was better incorporated by purified ZIKV NS5 polymerase over time. These findings suggest both a nucleobase and ProTide group bias for the anti-ZIKV activity of Nucleoside Analogue ProTides in a disease-relevant cell model.
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activity of selected Nucleoside Analogue protides against zika virus in human neural stem cells
bioRxiv, 2019Co-Authors: Jean A Bernatchez, Michael Coste, Sungjun Beck, Grace Wells, Lucas A Luna, Alex E Clark, Zhe Zhu, Christal D. SohlAbstract:Abstract Zika virus (ZIKV), an emerging flavivirus which causes neurodevelopmental impairment to fetuses and has been linked to Guillain-Barre syndrome, continues to threaten global health due to the absence of targeted prophylaxis or treatment. Nucleoside Analogues are good examples of efficient anti-viral inhibitors, and prodrug strategies using phosphate masking groups (ProTides) have been employed to improve the bioavailability of riboNucleoside Analogues. Here, we synthesized and tested a library of 13 ProTides against ZIKV in human neural stem cells. Strong activity was observed for 2′-C-methyluridine and 2′-C-ethynyluridine ProTides with an aryloxyl phosphoramidate masking group. Conversion of the aryloxyl phosphoramidate ProTide group of 2′-C-methyluridine to a 2-(methylthio)ethyl phosphoramidate completely abolished antiviral activity of the compound. The aryloxyl phosphoramidate ProTide of 2′-C-methyluridine outperformed the hepatitis C virus (HCV) drug sofosbuvir in suppression of viral titers and protection from cytopathic effect, while the former compound’s triphosphate active metabolite was better incorporated by purified ZIKV NS5 polymerase over time. Molecular superpositioning revealed different orientations of residues opposite the 2′-fluoro group of sofosbuvir. These findings suggest both a nucleobase and ProTide group bias for the anti-ZIKV activity of Nucleoside Analogue ProTides in a disease-relevant cell model.
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Activity of Selected Nucleoside Analogue ProTides against Zika Virus in Human Neural Stem Cells
MDPI AG, 2019Co-Authors: Jean A Bernatchez, Michael Coste, Sungjun Beck, Lucas A Luna, Alex E Clark, Zhe Zhu, David Hecht, Grace A. Wells, Jeremy N. Rich, Christal D. SohlAbstract:Zika virus (ZIKV), an emerging flavivirus that causes neurodevelopmental impairment to fetuses and has been linked to Guillain-Barré syndrome continues to threaten global health due to the absence of targeted prophylaxis or treatment. Nucleoside Analogues are good examples of efficient anti-viral inhibitors, and prodrug strategies using phosphate masking groups (ProTides) have been employed to improve the bioavailability of riboNucleoside Analogues. Here, we synthesized and tested a small library of 13 ProTides against ZIKV in human neural stem cells. Strong activity was observed for 2′-C-methyluridine and 2′-C-ethynyluridine ProTides with an aryloxyl phosphoramidate masking group. Substitution of a 2-(methylthio) ethyl phosphoramidate for the aryloxyl phosphoramidate ProTide group of 2′-C-methyluridine completely abolished antiviral activity of the compound. The aryloxyl phosphoramidate ProTide of 2′-C-methyluridine outperformed the hepatitis C virus (HCV) drug sofosbuvir in suppression of viral titers and protection from cytopathic effect, while the former compound’s triphosphate active metabolite was better incorporated by purified ZIKV NS5 polymerase over time. These findings suggest both a nucleobase and ProTide group bias for the anti-ZIKV activity of Nucleoside Analogue ProTides in a disease-relevant cell model
