The Experts below are selected from a list of 1269 Experts worldwide ranked by ideXlab platform
Yuming Wang - One of the best experts on this subject based on the ideXlab platform.
-
Telbivudine prevents vertical transmission of hepatitis b virus from women with high viral loads a prospective long term study
Clinical Gastroenterology and Hepatology, 2015Co-Authors: Hongfei Huang, Xiaowen Sun, Meimin Pan, Shun Tan, Yi Zeng, Guohong Deng, Zehui Yan, Yuming WangAbstract:Background & Aims Hepatitis B virus (HBV) infection is a leading cause of liver diseases. We investigated the efficacy and safety of Telbivudine in preventing transmission of HBV from hepatitis B e antigen–positive pregnant women with high viral loads to their infants in an open-label study. Methods We performed a prospective study of 450 hepatitis B e antigen–positive pregnant women with HBV DNA levels greater than 10 6 IU/mL; 279 women received Telbivudine (600 mg/d) during weeks 24 to 32 of gestation, and 171 women who were unwilling to take antiviral drugs participated as controls. All newborns were vaccinated with a recombinant HBV vaccine and hepatitis B immune globulin, according to a standard immunoprophylaxis procedure. Mother-to-child transmission of HBV was determined by detection of hepatitis B surface antigen and HBV DNA in the infant 6 months after birth. Results None of the infants whose mothers were given Telbivudine tested positive for of hepatitis B surface antigen at 6 months, compared with 14.7% of infants in the control group ( P = 5.317 × 10 -8 ). Levels of HBV DNA also decreased among women given Telbivudine; 40 of 172 (23.2%) women given Telbivudine had undetectable HBV DNA levels before delivery, compared with none of the controls. A significantly higher proportion of women given Telbivudine had undetectable levels of HBV DNA in cord blood (99.1%) than controls (61.5%; P = 1.195 × 10 -22 ). No severe adverse events or complications were observed in women or infants. Conclusions Telbivudine significantly reduces vertical transmission of HBV from pregnant women to their infants; it is safe and well tolerated by women and infants. Antiretroviral Pregnancy Registry Health Care Providers ID: 26592; Government number: Natural Science Foundation of China (NSFC) 30830090, 30972598; and Third Military Medical University Key Project for Clinical Research: 2012XLC05).
-
Telbivudine improves renal function in patients with chronic hepatitis b
Gastroenterology, 2014Co-Authors: Edward Gane, Yuming Wang, Yunfan Liaw, George V Papatheodoridis, Seng Gee Lim, C L Lai, J Rasenack, Gilbert Deray, Adrian M Di Bisceglie, Maria ButiAbstract:Background & Aims There is a close relationship between chronic hepatitis B virus infection and chronic renal disease. We analyzed changes in renal function using different markers of glomerular filtration rate (GFR) in multiple studies of Telbivudine treatment of patients with chronic hepatitis B virus infection. Methods We used serum creatinine-based equations (ie, Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration) to estimate GFR (eGFR) in adults with chronic hepatitis B virus infection and compensated liver disease who participated in a phase III, randomized, double-blind study comparing the efficacy and safety of Telbivudine (600 mg/d) and lamivudine (100 mg/d) for 2 years (the GLOBE study) and in long-term extension studies (4−6 years), as well as in patients with decompensated cirrhosis (2 years). Results eGFRs calculated using the Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equations were concordant, indicating improved renal function in Telbivudine-treated patients during the 2-year GLOBE study (there was an 8.5% increase in mean eGFR, based on the Modification of Diet in Renal Disease equation). Improved renal function was maintained for 4−6 years. Increased eGFR with Telbivudine treatment was also observed in patients at increased risk for renal impairment: patients with baseline eGFRs of 60−89 mL/min/1.73 m 2 (+17.2%), older than 50 years (+11.4%), and with liver fibrosis/cirrhosis (+7.2% for patients with Ishak fibrosis score at 5−6). In decompensated patients with high renal risk, eGFR was also improved on Telbivudine (+2.0%). Conclusions In global trials of patients with compensated and decompensated cirrhosis, long-term Telbivudine therapy was associated with a sustained improvement of renal function—particularly among patients with increased risk of renal impairment. The mechanisms of this renal protective effect remain to be determined.
-
two year results of a randomized phase iii comparative trial of Telbivudine versus lamivudine in chinese patients
Hepatology International, 2014Co-Authors: Jidong Jia, Yuming Wang, Junqi Niu, Deming Tan, Jinlin Hou, Youkuan Yin, X J Zhou, Limin Zhu, Chengwei Chen, Hong RenAbstract:The burden of chronic hepatitis B infection is high in China, where prevalence exceeds 7 %. This was a randomized, double-blinded, phase III study of the efficacy and safety of Telbivudine and lamivudine treatment at 104 weeks in Chinese patients with chronic hepatitis B. Hepatitis B e antigen-positive (n = 290) and -negative (n = 42) adults with nucleoside analog–naive compensated chronic hepatitis B were randomized to receive Telbivudine 600 mg/day or lamivudine 100 mg/day for 104 weeks. The primary endpoint was reduction from baseline in serum hepatitis B virus (HBV) DNA at week 52. Week 104 analyses included HBV DNA reductions, undetectable HBV DNA (<300 copies/mL), ALT normalization, and e-antigen loss/seroconversion. Efficacy at week 104 was also assessed as a function of week 24 HBV DNA. In the intention-to-treat population (n = 332) at week 104, Telbivudine was superior to lamivudine for reduction of HBV DNA [−5.48 vs. −4.00 log10 copies/mL; difference −1.49 log10 (95 % confidence interval −2.2, −0.8); p < 0.0001], for the proportion with undetectable HBV DNA (61.9 vs. 38.5 %; p < 0.0001), for ALT normalization (75.8 vs. 61.3 %; p = 0.0049), and for e-antigen loss (39.9 vs. 28.2 %; p = 0.0373). The cumulative probability of genotypic drug resistance was 15.4 % on Telbivudine versus 23.6 % on lamivudine through week 104. Early virologic response at week 24 was associated with improved outcomes at week 104. Adverse events were similar to those seen in the GLOBE study. Telbivudine is superior to lamivudine over 2 years of chronic hepatitis B treatment in Chinese patients.
-
efficacy and safety of continuous 4 year Telbivudine treatment in patients with chronic hepatitis b
Journal of Viral Hepatitis, 2013Co-Authors: Yuming Wang, Satawat Thongsawat, Edward Gane, Yunfan Liaw, Jidong Jia, J Hou, Hoiyun Chan, George V Papatheodoridis, Mobin Wan, Junqi NiuAbstract:In the phase-III GLOBE/015 studies, Telbivudine demonstrated superior efficacy vs lamivudine during 2-year treatment in HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB). After completion, 847 patients had an option to continue Telbivudine treatment for further 2 years. A total of 596 (70%) of Telbivudine-treated patients, who were serum HBV DNA positive or negative and without genotypic resistance to Telbivudine at the end of the GLOBE/015 trials, were enrolled into a further 2-year extension study. A group of 502 patients completed 4 years of continuous Telbivudine treatment and were included in the Telbivudine per-protocol population. Amongst 293 HBeAg-positive patients, 76.2% had undetectable serum HBV DNA and 86.0% had normal serum ALT at the end of 4 years. Notably, the cumulative rate of HBeAg seroconversion was 53.2%. Amongst 209 HBeAg-negative patients, 86.4% had undetectable HBV DNA and 89.6% had normal serum ALT. In patients who had discontinued Telbivudine treatment due to HBeAg seroconversion, the HBeAg response was durable in 82% of patients (median 111 weeks of off-treatment follow-up). The cumulative 4-year resistance rate was 10.6% for HBeAg-positive and 10.0% for HBeAg-negative patients. Most adverse events were mild or moderate in severity and transient. Renal function measured by estimated glomerular filtration rate (eGFR) increased by 14.9 mL/min/1.73 m(2) (16.6%) from baseline to 4 years (P < 0.0001). In conclusion, in HBeAg-positive and HBeAg-negative CHB patients without resistance after 2 years, two additional years of Telbivudine treatment continued to provide effective viral suppression with a favourable safety profile. Moreover, Telbivudine achieved 53% of HBeAg seroconversion in HBeAg-positive patients.
-
efficacy and safety of prolonged 3 year Telbivudine treatment in patients with chronic hepatitis b
Liver International, 2011Co-Authors: Edward Gane, Yuming Wang, Satawat Thongsawat, Yunfan Liaw, Jidong Jia, Mobin Wan, J L Hou, Young Myoung Moon, You C Chao, Junqi NiuAbstract:Background: In the GLOBE trial, Telbivudine demonstrated superior efficacy to lamivudine at 2 years in patients with chronic hepatitis B (CHB). Aims: To investigate the long-term efficacy and safety of Telbivudine in the Telbivudine-treated cohort from the GLOBE trial. Methods: Virological and biochemical responses were assessed in 213 HBeAg-positive and 186 HBeAg-negative CHB patients who continued Telbivudine treatment for 3 years. Results: Undetectable hepatitis B virus DNA and HBeAg seroconversions were achieved by 77 and 37% of HBeAg-positive patients respectively. Cumulative HBeAg seroconversion rate was 46%. HBeAg seroconversion was sustained at 52 weeks off therapy in 84% of the patients enrolled in the off-treatment follow-up arm of the study. Undetectable viraemia and normal alanine aminotransferase (ALT) levels at 3 years were achieved by 85 and 83% of HBeAg-negative patients respectively. Genotypic resistance rates for the study population who continued therapy during the third year were 11.3 in HBeAg-positive and 6.5% in HBeAg-negative patients. Patients with undetectable viraemia at treatment week 24 had optimal outcomes at 3 years. In the HBeAg-positive population, cumulative HBeAg seroconversion occurred in 58%. Resistance rates for HBeAg-positive and HBeAg-negative patients were 3.6 and 6.2% respectively. The Telbivudine safety profile during prolonged therapy was similar to that in the GLOBE trial. Conclusions: Three years of Telbivudine treatment yielded high rates of viral suppression and ALT normalization with a favourable safety profile. High rates of HBeAg seroconversion were achieved with prolonged Telbivudine therapy and were sustained in the majority of patients over 52 weeks off therapy.
Edward Gane - One of the best experts on this subject based on the ideXlab platform.
-
NA: Telbivudine versus lamivudine in patients with chronic hepatitis B
2016Co-Authors: Chinglung Lai, Stefan Zeuzem, George Chao, Edward Gane, Yunfan Liaw, Young Myoung Moon, Adrian M Di Bisceglie, Zachary Goodman, Ph. D, Barbara Fielman ConstanceAbstract:Title Telbivudine versus lamivudine in patients with chronic hepatitis
-
Telbivudine plus pegylated interferon alfa 2a in a randomized study in chronic hepatitis b is associated with an unexpected high rate of peripheral neuropathy
Journal of Hepatology, 2015Co-Authors: Patrick Marcellin, Edward Gane, K Wursthorn, Heiner Wedemeyer, Wanlong Chuang, George K K Lau, Claudio Avila, Chengyuan Peng, Seng Gee Lim, Hugo FainboimAbstract:Background & Aims This study investigated the antiviral efficacy and safety of Telbivudine in combination with pegylated interferon (PegIFN) alpha-2a in chronic hepatitis B (CHB) patients. Methods This was a randomized, open-label, multicentre study, in treatment-naive patients with HBeAg-positive CHB, comparing the efficacy and safety of Telbivudine in combination with PegIFN alpha-2a with Telbivudine monotherapy and PegIFN alpha-2a monotherapy. The study was terminated early due to increased rates of peripheral neuropathy in the combination-therapy group. Results Of the 159 patients randomized (from 300 planned) 50 were assigned to combination therapy, 55 to Telbivudine, 54 to PegIFN, and 110 (18, 49, and 43, respectively) reached week 24. Peripheral neuropathy occurred in 7/50, 1/54, and 0/54 patients in the three groups of safety populations, respectively. No relationship between the occurrence of peripheral neuropathy and other variables (e.g., pharmacokinetic data, treatment efficacy, ALT levels, creatine kinase elevations) were observed. At week 24, undetectable HBV DNA ( p =0.022 for combination therapy vs. Telbivudine; p vs. PegIFN). Conclusions Combination therapy carried an increased risk of peripheral neuropathy. Despite the rapid and profound reductions in HBV DNA levels, combination therapy with Telbivudine and PegIFN should not be used.
-
Telbivudine improves renal function in patients with chronic hepatitis b
Gastroenterology, 2014Co-Authors: Edward Gane, Yuming Wang, Yunfan Liaw, George V Papatheodoridis, Seng Gee Lim, C L Lai, J Rasenack, Gilbert Deray, Adrian M Di Bisceglie, Maria ButiAbstract:Background & Aims There is a close relationship between chronic hepatitis B virus infection and chronic renal disease. We analyzed changes in renal function using different markers of glomerular filtration rate (GFR) in multiple studies of Telbivudine treatment of patients with chronic hepatitis B virus infection. Methods We used serum creatinine-based equations (ie, Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration) to estimate GFR (eGFR) in adults with chronic hepatitis B virus infection and compensated liver disease who participated in a phase III, randomized, double-blind study comparing the efficacy and safety of Telbivudine (600 mg/d) and lamivudine (100 mg/d) for 2 years (the GLOBE study) and in long-term extension studies (4−6 years), as well as in patients with decompensated cirrhosis (2 years). Results eGFRs calculated using the Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equations were concordant, indicating improved renal function in Telbivudine-treated patients during the 2-year GLOBE study (there was an 8.5% increase in mean eGFR, based on the Modification of Diet in Renal Disease equation). Improved renal function was maintained for 4−6 years. Increased eGFR with Telbivudine treatment was also observed in patients at increased risk for renal impairment: patients with baseline eGFRs of 60−89 mL/min/1.73 m 2 (+17.2%), older than 50 years (+11.4%), and with liver fibrosis/cirrhosis (+7.2% for patients with Ishak fibrosis score at 5−6). In decompensated patients with high renal risk, eGFR was also improved on Telbivudine (+2.0%). Conclusions In global trials of patients with compensated and decompensated cirrhosis, long-term Telbivudine therapy was associated with a sustained improvement of renal function—particularly among patients with increased risk of renal impairment. The mechanisms of this renal protective effect remain to be determined.
-
efficacy and safety of continuous 4 year Telbivudine treatment in patients with chronic hepatitis b
Journal of Viral Hepatitis, 2013Co-Authors: Yuming Wang, Satawat Thongsawat, Edward Gane, Yunfan Liaw, Jidong Jia, J Hou, Hoiyun Chan, George V Papatheodoridis, Mobin Wan, Junqi NiuAbstract:In the phase-III GLOBE/015 studies, Telbivudine demonstrated superior efficacy vs lamivudine during 2-year treatment in HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB). After completion, 847 patients had an option to continue Telbivudine treatment for further 2 years. A total of 596 (70%) of Telbivudine-treated patients, who were serum HBV DNA positive or negative and without genotypic resistance to Telbivudine at the end of the GLOBE/015 trials, were enrolled into a further 2-year extension study. A group of 502 patients completed 4 years of continuous Telbivudine treatment and were included in the Telbivudine per-protocol population. Amongst 293 HBeAg-positive patients, 76.2% had undetectable serum HBV DNA and 86.0% had normal serum ALT at the end of 4 years. Notably, the cumulative rate of HBeAg seroconversion was 53.2%. Amongst 209 HBeAg-negative patients, 86.4% had undetectable HBV DNA and 89.6% had normal serum ALT. In patients who had discontinued Telbivudine treatment due to HBeAg seroconversion, the HBeAg response was durable in 82% of patients (median 111 weeks of off-treatment follow-up). The cumulative 4-year resistance rate was 10.6% for HBeAg-positive and 10.0% for HBeAg-negative patients. Most adverse events were mild or moderate in severity and transient. Renal function measured by estimated glomerular filtration rate (eGFR) increased by 14.9 mL/min/1.73 m(2) (16.6%) from baseline to 4 years (P < 0.0001). In conclusion, in HBeAg-positive and HBeAg-negative CHB patients without resistance after 2 years, two additional years of Telbivudine treatment continued to provide effective viral suppression with a favourable safety profile. Moreover, Telbivudine achieved 53% of HBeAg seroconversion in HBeAg-positive patients.
-
randomized clinical trial efficacy and safety of Telbivudine and lamivudine in treatment naive patients with hbv related decompensated cirrhosis
Journal of Viral Hepatitis, 2012Co-Authors: Hoiyun Chan, Teerha Piratvisuth, Yicheng Chen, Edward Gane, Shiv Kumar Sarin, Dong Jin Suh, B Prabhakar, S G Hwang, Gourdas Choudhuri, Rifaat SafadiAbstract:Patients with decompensated cirrhosis owing to chronic hepatitis B viral (HBV) infection have a high morbidity/mortality rate, and the treatment remains a challenge. We studied the safety and efficacy of Telbivudine and lamivudine in such patients. This noninferiority, double-blind trial randomized 232 treatment-naive patients with decompensated HBV (1:1) in 80 academic hospitals to receive once-daily Telbivudine 600 mg or lamivudine 100 mg for 104 weeks. Primary composite endpoint was proportion of patients with HBV DNA <10 000 copies/mL, normal alanine aminotransferase (ALT) and Child-Turcotte-Pugh score improvement/stabilization at week 52. Response rates using a post hoc modified endpoint (HBV DNA <300 copies/mL [57 IU/mL] and ALT normalization) in intent-to-treat analysis (missing = failure) were 56.3%vs 38.0% after 76 weeks (P = 0.018) and 45.6%vs 32.9% after 104 weeks (P = 0.093) for Telbivudine vs lamivudine. Telbivudine treatment was an independent predictive factor for HBV DNA <300 copies/mL and ALT normalization (P = 0.037). Response rates with protocol-defined composite endpoint in intent-to-treat analysis (M = F) were 56.2 vs 54.0% (noninferiority not achieved) and 39.1%vs 36.4% (noninferiority achieved) in Telbivudine and lamivudine groups at 52 and 104 weeks. Telbivudine treatment was associated with a significant improvement in glomerular filtration rate compared to lamivudine treatment and was also associated with a trend for improvement in survival (87%vs 79%). No cases of lactic acidosis were reported. Telbivudine compared to lamivudine was associated with a higher rate of patients with both viral suppression and ALT normalization, a trend towards a higher rate of survival and significant improvement in glomerular filtration.
Guorong Han - One of the best experts on this subject based on the ideXlab platform.
-
long term safety and efficacy of Telbivudine in infants born to mothers treated during the second or third trimesters of pregnancy
Journal of Viral Hepatitis, 2017Co-Authors: Guorong Han, Hongxiu Jiang, Cuimin Wang, Xin Yue, Genju Wang, Yi Ding, Liu Zhou, Wei ZhaoAbstract:Summary Telbivudine, an FDA pregnancy category B drug, has been found to reduce hepatitis B virus (HBV) perinatal transmission with no safety concerns in infants aged up to 1 year. This study evaluated the long-term efficacy and safety of Telbivudine in 214 infants born to 210 pregnant women with chronic hepatitis B infection who were treated with Telbivudine during pregnancy (weeks 20-32 of gestation). The infants were followed for up to 5 years after birth. The efficacy endpoint was the rate of perinatal transmission, which was established by HBsAg and HBV DNA levels at 7 and 12 months. Safety endpoints included head circumference, weight, height, and congenital abnormality and hospitalization rates. In addition, the Denver Developmental Screening Test was performed in 92 randomly selected infants. None of the 214 infants born to these women were infected with HBV, and all had effective serum hepatitis B surface antibody (HBsAb) levels. Compared with Chinese standard values, there were few differences in the infants’ mean head circumference, weight, and height values. No birth defects were diagnosed, and the congenital abnormality rate was 0.934%. Serious adverse events requiring hospitalization occurred in 20 infants (9.35%). The qualified Denver Developmental Screening Test rate in 92 infants was 97.82%, which was comparable to a rate of 92% in normal Chinese children. Thus, treatment with Telbivudine during the second or third trimesters of pregnancy safely blocked perinatal transmission of HBV. Infants born to Telbivudine-treated mothers showed normal growth and development during long-term follow-up of up to 5 years. This article is protected by copyright. All rights reserved.
-
comprehensive review of Telbivudine in pregnant women with chronic hepatitis b
World Journal of Hepatology, 2016Co-Authors: Teerha Piratvisuth, Guorong Han, Stanislas Pol, Yuhong Dong, Aldo TrylesinskiAbstract:CONCLUSION: Telbivudine treatment during pregnancy presents a favorable safety profile without increased rates of live birth defects, spontaneous abortion or elective termination, or fetal/neonatal toxicity. Exposure to Telbivudine in the first, second and third trimester of pregnancy has been shown to significantly reduce the risk of HBV transmission from mother to child on the basis of standard immune prophylaxis procedure.
-
Telbivudine prevents vertical transmission from hbeag positive women with chronic hepatitis b
Clinical Gastroenterology and Hepatology, 2012Co-Authors: Calvin Q Pan, M Cao, Guorong Han, Wei Zhao, Hongxiu Jiang, Cuimin Wang, Xin Yue, Genju WangAbstract:Background & Aims Telbivudine reduces hepatitis B virus (HBV) DNA and normalizes levels of alanine aminotransferase (ALT) in patients with chronic hepatitis B (CHB). We investigated its use in preventing vertical transmission. Methods We performed an open-label, prospective study of 88 hepatitis B (HB) e antigen (HBeAg)-positive pregnant women with CHB, levels of HBV DNA >6 log10 copies/mL, and increased levels of ALT. Women were given Telbivudine (n = 53) starting in the 2nd or 3rd trimester, or no treatment (controls, n=35) and followed until postpartum week (PPW) 28. All infants received standard immunoprophylaxis after birth. Results At 28 weeks, none of the infants whose mothers received Telbivudine had immunoprophylaxis failure, whereas 8.6% of the infants of control mothers did (P = .029). There were no differences between groups in mothers' adverse events or infants' congenital deformities, gestational age, height, and weight, or Apgar scores. At postpartum week 28, significantly more Telbivudine-treated mothers had levels of HBV DNA 1 log10 increase from 10 times the upper limit of normal) in either group during 28 weeks of postpartum observation. Conclusions Women with CHB given Telbivudine during the second or third trimester of pregnancy have reduced rates of perinatal transmission. Telbivudine produced no adverse events in mothers or infants by 28 weeks.
-
a prospective and open label study for the efficacy and safety of Telbivudine in pregnancy for the prevention of perinatal transmission of hepatitis b virus infection
Journal of Hepatology, 2011Co-Authors: Guorong Han, M Cao, Wei Zhao, Hongxiu Jiang, Cuimin Wang, Shufen Bai, Xin Yue, Genju Wang, Xun Tang, Zhixun FangAbstract:Background & Aims In the Asia–Pacific region, perinatal transmission of the hepatitis B virus (HBV) is the primary cause of chronic hepatitis B infection. Despite the use of HBIG and HBV vaccination, HBV perinatal transmission (PT) occurs in 10–30% of infants born to highly viremic mothers. We evaluated the efficacy and safety of LTD use during late pregnancy in reducing HBV transmission in highly viremic HBeAg+mothers. Methods Two hundred and twenty-nine HBeAg+HBV DNA levels>1.0×10 7 copies/ml mothers received Telbivudine 600mg/day from week 20 to 32 of gestation (n=135) or served as untreated controls (n=94). All infants in both arms received 200IU of HBIg within 12h postpartum and recombinant HBV vaccine of 20μg at 0, 1, and 6months. HBsAg and HBV DNA results of infants at week 28 were used to determine perinatal transmission rate. All Telbivudine treated subjects were registered in the Antiretroviral Pregnancy Registry. Results Telbivudine treatment was associated with a marked reduction in serum HBV DNA and hepatitis B e antigen (HBeAg) levels and normalization of elevated ALT levels before delivery. A striking decline of HBV DNA levels started from treatment onset to week 4, and sustained in a low level since week 12. Forty-four (33%) of the 135 Telbivudine-treated mothers and none (0%) of the untreated controls had polymerase chain reaction-undetectable viremia (DNA vs . 8%; p =0.002). HBV DNA levels were only detectable in HBsAg+infants. No significant differences in anti-HBs levels were observed during postnatal follow-up. No serious adverse events were noted in the Telbivudine-treated mothers or their infants. Conclusions Telbivudine used during pregnancy in CHB HBeAg+highly viremic mothers can safely reduce perinatal HBV transmission. Telbivudine was well-tolerated with no safety concerns in the Telbivudine-treated mothers or their infants on short term follow up. These data support the use of Telbivudine in this special population.
Genju Wang - One of the best experts on this subject based on the ideXlab platform.
-
long term safety and efficacy of Telbivudine in infants born to mothers treated during the second or third trimesters of pregnancy
Journal of Viral Hepatitis, 2017Co-Authors: Guorong Han, Hongxiu Jiang, Cuimin Wang, Xin Yue, Genju Wang, Yi Ding, Liu Zhou, Wei ZhaoAbstract:Summary Telbivudine, an FDA pregnancy category B drug, has been found to reduce hepatitis B virus (HBV) perinatal transmission with no safety concerns in infants aged up to 1 year. This study evaluated the long-term efficacy and safety of Telbivudine in 214 infants born to 210 pregnant women with chronic hepatitis B infection who were treated with Telbivudine during pregnancy (weeks 20-32 of gestation). The infants were followed for up to 5 years after birth. The efficacy endpoint was the rate of perinatal transmission, which was established by HBsAg and HBV DNA levels at 7 and 12 months. Safety endpoints included head circumference, weight, height, and congenital abnormality and hospitalization rates. In addition, the Denver Developmental Screening Test was performed in 92 randomly selected infants. None of the 214 infants born to these women were infected with HBV, and all had effective serum hepatitis B surface antibody (HBsAb) levels. Compared with Chinese standard values, there were few differences in the infants’ mean head circumference, weight, and height values. No birth defects were diagnosed, and the congenital abnormality rate was 0.934%. Serious adverse events requiring hospitalization occurred in 20 infants (9.35%). The qualified Denver Developmental Screening Test rate in 92 infants was 97.82%, which was comparable to a rate of 92% in normal Chinese children. Thus, treatment with Telbivudine during the second or third trimesters of pregnancy safely blocked perinatal transmission of HBV. Infants born to Telbivudine-treated mothers showed normal growth and development during long-term follow-up of up to 5 years. This article is protected by copyright. All rights reserved.
-
Telbivudine prevents vertical transmission from hbeag positive women with chronic hepatitis b
Clinical Gastroenterology and Hepatology, 2012Co-Authors: Calvin Q Pan, M Cao, Guorong Han, Wei Zhao, Hongxiu Jiang, Cuimin Wang, Xin Yue, Genju WangAbstract:Background & Aims Telbivudine reduces hepatitis B virus (HBV) DNA and normalizes levels of alanine aminotransferase (ALT) in patients with chronic hepatitis B (CHB). We investigated its use in preventing vertical transmission. Methods We performed an open-label, prospective study of 88 hepatitis B (HB) e antigen (HBeAg)-positive pregnant women with CHB, levels of HBV DNA >6 log10 copies/mL, and increased levels of ALT. Women were given Telbivudine (n = 53) starting in the 2nd or 3rd trimester, or no treatment (controls, n=35) and followed until postpartum week (PPW) 28. All infants received standard immunoprophylaxis after birth. Results At 28 weeks, none of the infants whose mothers received Telbivudine had immunoprophylaxis failure, whereas 8.6% of the infants of control mothers did (P = .029). There were no differences between groups in mothers' adverse events or infants' congenital deformities, gestational age, height, and weight, or Apgar scores. At postpartum week 28, significantly more Telbivudine-treated mothers had levels of HBV DNA 1 log10 increase from 10 times the upper limit of normal) in either group during 28 weeks of postpartum observation. Conclusions Women with CHB given Telbivudine during the second or third trimester of pregnancy have reduced rates of perinatal transmission. Telbivudine produced no adverse events in mothers or infants by 28 weeks.
-
a prospective and open label study for the efficacy and safety of Telbivudine in pregnancy for the prevention of perinatal transmission of hepatitis b virus infection
Journal of Hepatology, 2011Co-Authors: Guorong Han, M Cao, Wei Zhao, Hongxiu Jiang, Cuimin Wang, Shufen Bai, Xin Yue, Genju Wang, Xun Tang, Zhixun FangAbstract:Background & Aims In the Asia–Pacific region, perinatal transmission of the hepatitis B virus (HBV) is the primary cause of chronic hepatitis B infection. Despite the use of HBIG and HBV vaccination, HBV perinatal transmission (PT) occurs in 10–30% of infants born to highly viremic mothers. We evaluated the efficacy and safety of LTD use during late pregnancy in reducing HBV transmission in highly viremic HBeAg+mothers. Methods Two hundred and twenty-nine HBeAg+HBV DNA levels>1.0×10 7 copies/ml mothers received Telbivudine 600mg/day from week 20 to 32 of gestation (n=135) or served as untreated controls (n=94). All infants in both arms received 200IU of HBIg within 12h postpartum and recombinant HBV vaccine of 20μg at 0, 1, and 6months. HBsAg and HBV DNA results of infants at week 28 were used to determine perinatal transmission rate. All Telbivudine treated subjects were registered in the Antiretroviral Pregnancy Registry. Results Telbivudine treatment was associated with a marked reduction in serum HBV DNA and hepatitis B e antigen (HBeAg) levels and normalization of elevated ALT levels before delivery. A striking decline of HBV DNA levels started from treatment onset to week 4, and sustained in a low level since week 12. Forty-four (33%) of the 135 Telbivudine-treated mothers and none (0%) of the untreated controls had polymerase chain reaction-undetectable viremia (DNA vs . 8%; p =0.002). HBV DNA levels were only detectable in HBsAg+infants. No significant differences in anti-HBs levels were observed during postnatal follow-up. No serious adverse events were noted in the Telbivudine-treated mothers or their infants. Conclusions Telbivudine used during pregnancy in CHB HBeAg+highly viremic mothers can safely reduce perinatal HBV transmission. Telbivudine was well-tolerated with no safety concerns in the Telbivudine-treated mothers or their infants on short term follow up. These data support the use of Telbivudine in this special population.
C L Lai - One of the best experts on this subject based on the ideXlab platform.
-
Telbivudine improves renal function in patients with chronic hepatitis b
Gastroenterology, 2014Co-Authors: Edward Gane, Yuming Wang, Yunfan Liaw, George V Papatheodoridis, Seng Gee Lim, C L Lai, J Rasenack, Gilbert Deray, Adrian M Di Bisceglie, Maria ButiAbstract:Background & Aims There is a close relationship between chronic hepatitis B virus infection and chronic renal disease. We analyzed changes in renal function using different markers of glomerular filtration rate (GFR) in multiple studies of Telbivudine treatment of patients with chronic hepatitis B virus infection. Methods We used serum creatinine-based equations (ie, Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration) to estimate GFR (eGFR) in adults with chronic hepatitis B virus infection and compensated liver disease who participated in a phase III, randomized, double-blind study comparing the efficacy and safety of Telbivudine (600 mg/d) and lamivudine (100 mg/d) for 2 years (the GLOBE study) and in long-term extension studies (4−6 years), as well as in patients with decompensated cirrhosis (2 years). Results eGFRs calculated using the Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equations were concordant, indicating improved renal function in Telbivudine-treated patients during the 2-year GLOBE study (there was an 8.5% increase in mean eGFR, based on the Modification of Diet in Renal Disease equation). Improved renal function was maintained for 4−6 years. Increased eGFR with Telbivudine treatment was also observed in patients at increased risk for renal impairment: patients with baseline eGFRs of 60−89 mL/min/1.73 m 2 (+17.2%), older than 50 years (+11.4%), and with liver fibrosis/cirrhosis (+7.2% for patients with Ishak fibrosis score at 5−6). In decompensated patients with high renal risk, eGFR was also improved on Telbivudine (+2.0%). Conclusions In global trials of patients with compensated and decompensated cirrhosis, long-term Telbivudine therapy was associated with a sustained improvement of renal function—particularly among patients with increased risk of renal impairment. The mechanisms of this renal protective effect remain to be determined.
-
Extrahepatic effects of nucleoside and nucleotide analogues in chronic hepatitis B treatment
'Wiley', 2014Co-Authors: Fung Jyy, Seto Wkw, Yuen Rmf, C L LaiAbstract:Oral nucleoside/nucleotide analogues (NAs) are the mainstay of therapy for patients with chronic hepatitis B, and are generally well tolerated. Despite this, the safety profile of NAs is of paramount importance since the majority of patients will require long-term treatment. All NAs can potentially affect human DNA polymerase with decrease in mitochondrial DNA, leading to manifestations of mitochondrial toxicity. As a class effect therefore, NAs can potentially cause extra-hepatic conditions such as myopathy, nephropathy, neuropathy, and lactic acidosis. Indeed, effects on muscles including myopathy and creatine kinase elevations have been described with clevudine and Telbivudine use. Both adefovir and tenofovir are associated with dose-dependent nephropathy, predominantly affecting the proximal renal tubules. Neuropathy appears to be rare, and most commonly reported in patients receiving combination therapy with Telbivudine and interferon. Increased risk of lactic acidosis has also been described for those with impaired liver and renal function taking entecavir. Loss of bone mineral density and hypophosphatemia has been described with the use of nucleotide analogues, although the overwhelming studies have been with HIV-infected patients. However, not all extra-hepatic effects are detrimental. Recent evidence has suggested a potential renal beneficial effect with the use of Telbivudine. The effect of NAs on pregnancy appears to be minimal for all NAs, with Telbivudine and tenofovir having a more favorable category B rating. Ongoing pharmacovigilance is essential to identify new and monitor existing extra-hepatic effects associated with NA use.link_to_OA_fulltex
-
significance of hbv dna levels at 12 weeks of Telbivudine treatment and the 3 years treatment outcome
Journal of Hepatology, 2011Co-Authors: Wai-kay Seto, James Fung, C L Lai, Danny Kaho Wong, John Chihang Yuen, Ivan Hung, Man-fung YuenAbstract:Background & Aims The significance of early HBV DNA suppression during Telbivudine treatment in predicting long-term outcomes needs further investigation. Methods We determined the cumulative rates of HBeAg seroconversion, ALT normalization, HBV DNA suppression ( Results The median age and duration of follow-up were 39years and 24.2months, respectively. 117, 105, 69, and 43 patients had been followed up for at least 6months and 1, 2, and 3years, respectively. The cumulative rates of HBeAg seroconversion, ALT normalization, HBV DNA undetectability were 46.8%, 80.5%, and 51.2%, respectively, at 3years. There was an incremental increase in virologic breakthroughs to 39.5% by year 3. The cumulative rate of Telbivudine resistant mutations was 4.8%, 17.6%, and 34.0% for year 1, 2, and 3, respectively. Week 12 HBV DNA of p= 0.022) and lower chance of resistance ( p= 0.001) by year 3. Undetectable HBV DNA at week 24 was predictive of viral suppression at year 2 ( p 0.001) but not at year 3 ( p= 0.241). Conclusions Continuous Telbivudine resulted in improved biochemical and virologic outcomes, although there was an incremental increase in cumulative rate of resistance up to year 3. Week 12 HBV DNA of
-
safety evaluation of Telbivudine
Expert Opinion on Drug Safety, 2010Co-Authors: David But, Man-fung Yuen, James Fung, C L LaiAbstract:Importance of the field: Successful treatment of chronic hepatitis B (CHB) often requires long-term oral nucleoside/nucleotide agents which can be associated with viral resistance, patient non-compliance and adverse effects. Telbivudine is one of the more potent options available, with a 6.5- to 6.6-log copies/ml hepatitis B DNA reduction at 12 weeks in an early viral kinetic study, a potency comparable to entecavir. It is also one of the few drugs in the treatment of CHB under FDA pregnancy Category B.Areas covered in this review: The efficacy and safety profile of Telbivudine in compensated and decompensated CHB patients compared to other agents are discussed. Viral resistance, characteristic adverse effects including elevation in creatine kinase and peripheral neuropathy in Telbivudine treatment are reviewed. Infrequent but significant adverse effects of other nucleoside/nucleotide analogs are highlighted.What the reader will gain: Readers are provided the latest update on the clinical profile of long-...
-
pharmacokinetics of Telbivudine following oral administration of escalating single and multiple doses in patients with chronic hepatitis b virus infection pharmacodynamic implications
Antimicrobial Agents and Chemotherapy, 2006Co-Authors: Xiaojian Zhou, George C Chao, D. Lloyd, Seng Gee Lim, Nathaniel A Brown, C L LaiAbstract:The pharmacokinetics of Telbivudine were evaluated in adult patients with chronic hepatitis B virus (HBV) infection following once-daily oral administration at escalating doses of 25, 50, 100, 200, 400, and 800 mg/day for 4 weeks. Telbivudine was rapidly absorbed after oral administration, with the median times T(max) to the maximum plasma concentration (C(max)) ranging from 0.8 to 3.0 h postdosing across cohorts. Single-dose and steady-state maximum C(max)s and the areas under the plasma concentration-time curve from time zero to time t (AUC(0-t)s) increased proportionally with dose. At steady-state, the values of C(max) and AUC(0-t) were higher than those obtained after the administration of a single dose, indicative of a slight accumulation, with the ratios of the steady-state value to the value after the administration of a single dose ranging from 1.14 to 1.49 for C(max) and from 1.40 to 1.70 for AUC(0-t). While the elimination of Telbivudine from plasma was apparently monophasic over the 8-h sampling period, the substantial steady-state trough plasma levels observed in the groups receiving doses of 100 to 800 mg were clearly indicative of the presence of a second slower elimination phase, with the mean estimated half-lives ranging from 29.5 to 41.3 h by compartmental modeling analysis. Pharmacokinetic and pharmacodynamic analyses by using maximum-effect modeling established a quantitative relationship between a reduction in serum HBV DNA levels and parameters of drug exposure, in particular, the steady-state C(max) and AUC(0-t). In summary, this study showed that Telbivudine exhibits dose-proportional plasma pharmacokinetics with sustained steady-state drug exposure and exposure-related antiviral activity, supporting the need for further clinical studies by use of a once-daily regimen in patients with chronic HBV infection.
