The Experts below are selected from a list of 10356 Experts worldwide ranked by ideXlab platform

Tingtsung Chang - One of the best experts on this subject based on the ideXlab platform.

  • long term safety and tolerability of Entecavir in patients with chronic hepatitis b in the rollover study etv 901
    Expert Opinion on Drug Safety, 2012
    Co-Authors: Michael P Manns, Seung Kew Yoon, Suzanne Beebe, Tingtsung Chang, Naoky Tsai, Ulus Salih Akarca, William Sievert, Albert D Min, Andreas Pangerl, Suchat Wongcharatrawee
    Abstract:

    Objective: To review long-term safety data from the rollover study ETV-901, focusing on adverse events (AEs) with a potential nucleos(t)ide association. Methods: The open-label study ETV-901 (AI463901) assessed the safety of Entecavir in chronic hepatitis B patients who received Entecavir, lamivudine or adefovir monotherapy in previous Entecavir Phase II/III studies. Long-term cumulative safety results are based on reported AEs, regardless of causal relationship. Results: Median exposure to Entecavir in study ETV-901 was 184 weeks. Commonly reported AEs (≥ 10%) were upper respiratory tract infection, headache and nasopharyngitis. Most AEs were mild to moderate; 203 (19%) patients reported grade 3 – 4 AEs, with 45 (4%) considered related to Entecavir. There were 14 (1%) discontinuations due to AEs. On-treatment alanine aminotransferase (ALT) flares were reported in 32 (3%) patients and were associated with a reduction in hepatitis B virus DNA of more than 2 log10 copies/ml in 25/32 patients. AEs potentiall...

  • Entecavir treatment for up to 5 years in patients with hepatitis b e antigen positive chronic hepatitis b
    Hepatology, 2010
    Co-Authors: Tingtsung Chang, Seung Kew Yoon, Henrique Sergio Moraes Coelho, Flair Jose Carrilho, Fred Poordad, Waldemar Halota, Yves Horsmans, Naoky Tsai, Hui Zhang, Daniel J Tenney
    Abstract:

    Sustained virologic suppression is a primary goal of therapy for chronic hepatitis B (CHB). In study Entecavir (ETV)-022, 48 weeks of Entecavir 0.5 mg was superior to lamivudine for virologic suppression for hepatitis B e antigen (HBeAg)-positive CHB. A total of 183 Entecavir-treated patients from ETV-022 subsequently enrolled in study ETV-901. We present the results after up to 5 years (240 weeks) of continuous Entecavir therapy. The Entecavir long-term cohort consists of patients who received ≥1 year of Entecavir 0.5 mg in ETV-022 and then entered ETV-901 with a treatment gap ≤35 days. In ETV-901 the Entecavir dose was 1.0 mg daily. For patients with samples available at Year 5, proportions with hepatitis B virus (HBV) DNA <300 copies/mL, normal alanine aminotransferase (ALT) levels, HBeAg loss, and HBeAg seroconversion were determined. In all, 146 patients met criteria for inclusion in the Entecavir long-term cohort. At Year 5, 94% (88/94) had HBV DNA <300 copies/mL and 80% (78/98) had normal ALT levels. In addition to patients who achieved serologic responses during study ETV-022, 23% (33/141) achieved HBeAg seroconversion and 1.4% (2/145) lost hepatitis B surface antigen (HBsAg) during study ETV-901. Through 5 years, Entecavir resistance emerged in one patient. The safety profile of Entecavir was consistent with previous reports. Conclusion: Extended therapy with Entecavir through 5 years maintained or increased rates of HBV DNA suppression and ALT normalization. Additional patients also achieved HBeAg loss and seroconversion. Entecavir provides sustained viral suppression with minimal resistance during long-term treatment of HBeAg-positive CHB. (HEPATOLOGY 2010.)

  • relapse of hepatitis b in hbeag negative chronic hepatitis b patients who discontinued successful Entecavir treatment the case for continuous antiviral therapy
    Journal of Hepatology, 2009
    Co-Authors: Daniel Shouval, Paul Martin, Tingtsung Chang, Daniel J Tenney, Hugo Cheinquer, Giampiero Carosi, Sabahattin Kaymakoglu, Ricardo Tamez, Joanna Yang, H Brettsmith
    Abstract:

    BACKGROUND/AIMS: To evaluate the off-treatment durability of response in HBeAg-negative chronic hepatitis B patients who achieved a protocol-defined 'Response' (HBV-DNA<0.7MEq/mL and ALT<1.25xULN) with Entecavir at 48 weeks and the efficacy of Entecavir in patients treated beyond one year. METHODS: Entecavir-treated and lamivudine-treated patients who achieved a protocol-defined 'Response' were evaluated off-treatment for HBV-DNA<300copies/mL and ALT normalisation. Entecavir- and lamivudine-treated patients who achieved a protocol-defined 'Virological Response' (HBV-DNA<0.7MEq/mL but ALT1.25xULN) at 48 weeks, continued blinded treatment until they achieved Response or 96 weeks, whichever came first. RESULTS: Among 'Responders' who discontinued treatment after 48 weeks, 7/257 (3%) Entecavir-treated and 10/201 (5%) lamivudine-treated patients sustained HBV-DNA below 300copies/mL at 24-weeks off-treatment. Among the 54 patients who continued blinded treatment in the second year, 7/26 (27%) Entecavir-treated and 6/28 (21%) lamivudine-treated patients normalised ALT and 22/26 (85%) Entecavir-treated and 16/28 (57%) lamivudine-treated patients maintained HBV-DNA<300copies/mL at end-of-dosing. The safety profiles of both drugs remained comparable through a second year of treatment. CONCLUSIONS: The majority of protocol-defined Responders relapsed after 1 year when treatment was discontinued. Treatment with Entecavir beyond 1 year provided continued virological and biochemical benefit.

  • relapse of hepatitis b in hbeag negative chronic hepatitis b patients who discontinued successful Entecavir treatment the case for continuous antiviral therapy
    Journal of Hepatology, 2009
    Co-Authors: Daniel Shouval, Paul Martin, Tingtsung Chang, Hugo Cheinquer, Giampiero Carosi, Sabahattin Kaymakoglu, Ricardo Tamez, Ching-lung Lai, Steven Han, Joanna Yang
    Abstract:

    Background/Aims To evaluate the off-treatment durability of response in HBeAg-negative chronic hepatitis B patients who achieved a protocol-defined ‘ Response ' (HBV-DNA Methods Entecavir-treated and lamivudine-treated patients who achieved a protocol-defined ‘ Response ' were evaluated off-treatment for HBV-DNA Virological Response ' (HBV-DNA Response or 96 weeks, whichever came first. Results Among ‘ Responders ' who discontinued treatment after 48 weeks, 7/257 (3%) Entecavir-treated and 10/201 (5%) lamivudine-treated patients sustained HBV-DNA below 300copies/mL at 24-weeks off-treatment. Among the 54 patients who continued blinded treatment in the second year, 7/26 (27%) Entecavir-treated and 6/28 (21%) lamivudine-treated patients normalised ALT and 22/26 (85%) Entecavir-treated and 16/28 (57%) lamivudine-treated patients maintained HBV-DNA Conclusions The majority of protocol-defined Responders relapsed after 1 year when treatment was discontinued. Treatment with Entecavir beyond 1 year provided continued virological and biochemical benefit.

  • Entecavir therapy for up to 96 weeks in patients with hbeag positive chronic hepatitis b
    Gastroenterology, 2007
    Co-Authors: Robert G Gish, You Chen Chao, Adrian Gadano, Jose D Sollano, Tingtsung Chang, Anna S F Lok, Robert A De Man, Kwang Hyub Han, Shoudong Lee, Melissa Harris
    Abstract:

    Background & Aims: Entecavir demonstrated superior benefit to lamivudine at 48 weeks in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB). We evaluated continued Entecavir and lamivudine treatment through 96 weeks. Methods: 709 HBeAg-positive CHB patients were randomized to Entecavir 0.5 mg (n = 354) or lamivudine 100 mg (n = 355) once daily. At week 52, protocol-defined virologic responders could continue blinded treatment for up to 96 weeks. Patients continuing in year 2 (Entecavir, n = 243; lamivudine, n = 164) were assessed for serum hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT) normalization, HBeAg seroconversion, and safety. Cumulative confirmed proportions of all treated patients who achieved these responses were also analyzed. Results: Among patients treated in year 2, 74% of Entecavir-treated versus 37% of lamivudine-treated patients achieved HBV DNA <300 copies/mL by polymerase chain reaction (PCR), and 79% of Entecavir-treated versus 68% of lamivudine-treated patients normalized ALT levels. Similar proportions of Entecavir-treated and lamivudine-treated patients achieved HBeAg seroconversion (11% vs 12%, respectively). Higher proportions of Entecavir-treated than lamivudine-treated patients achieved cumulative confirmed HBV DNA <300 copies/mL by PCR (80% vs 39%; P < .0001) and ALT normalization (87% vs 79%; P = .0056) through 96 weeks. Cumulative confirmed HBeAg seroconversion occurred in 31% of Entecavir-treated versus 25% of lamivudine-treated patients (P = NS). Through 96 weeks, no patient experienced virologic breakthrough due to Entecavir resistance. The safety profile was comparable in both groups. Conclusions: Entecavir treatment through 96 weeks results in continued benefit for patients with HBeAg-positive CHB.

Wang Jiping - One of the best experts on this subject based on the ideXlab platform.

  • Organic anion and cation transporters are possibly involved in renal excretion of Entecavir in rats.
    Life sciences, 2011
    Co-Authors: Chen Yanxiao, Xu Ruijuan, Yang Jin, Chen Lei, Wang Qian, Yin Xuefen, Tang Hong, Zhang Xueying, Andrew K Davey, Wang Jiping
    Abstract:

    The purpose of the present study was to investigate the roles of transporters in the renal excretion of Entecavir. We analyzed the effect of probenecid, cimetidine, sulfobromophthalein sodium (BSP), verapamil, inhibitors of organic anion transporter (OAT), organic cation transporter (OCT), multidrug resistance-associated protein 2 (MRP2) and P-glycoprotein respectively, on the excretion of Entecavir. The area under plasma concentration-time curve (AUC), body clearance, and renal clearance of Entecavir was examined in each group. After intravenous coadministration with Entecavir in conscious rats, cimetidine, probenecid, BSP and verapamil significantly increased the AUC of Entecavir by 40.07%, 48.78%, 37.49%, and 54.58%, and reduced the body clearance by 27.14%, 31.69%, 29.79%, and 42.17%, respectively. Then the effects of these inhibitors on the renal clearance of Entecavir in unconscious rats were studied. Coadministration of cimetidine and probenecid increased the steady plasma concentration of Entecavir by 127.61% and 169.46%, reduced the renal clearance by 50.47% and 67.76%, and decreased the excretion ratio by 44.81% and 64.16% compared to initial values. However, the effects of BSP and verapamil were slight. Cimetidine and probenecid also increased the concentration of Entecavir in kidney from 34.00±0.80ng/mL to 55.19±4.92ng/mL and 49.92±1.53ng/mL, while the concentration of Entecavir in kidney from BSP and verapamil groups was 30.96±0.81ng/mL and 35.72±7.30ng/mL, respectively. These results suggest that cimetidine and probenecid inhibit the renal excretion of Entecavir in rats, which indicates the most likely involvement of organic anion and cation transporters in the renal excretion of Entecavir. Copyright © 2011 Elsevier Inc. All rights reserved.

  • Organic anion and cation transporters are possibly involved in renal excretion of Entecavir in rats
    Life Sciences, 2011
    Co-Authors: Chen Yanxiao, Xu Ruijuan, Yang Jin, Chen Lei, Wang Qian, Yin Xuefen, Tang Hong, Zhang Xueying, Andrew K Davey, Wang Jiping
    Abstract:

    Abstract Aims The purpose of the present study was to investigate the roles of transporters in the renal excretion of Entecavir. Main methods We analyzed the effect of probenecid, cimetidine, sulfobromophthalein sodium (BSP), verapamil, inhibitors of organic anion transporter (OAT), organic cation transporter (OCT), multidrug resistance-associated protein 2 (MRP2) and P-glycoprotein respectively, on the excretion of Entecavir. The area under plasma concentration–time curve (AUC), body clearance, and renal clearance of Entecavir was examined in each group. Key findings After intravenous coadministration with Entecavir in conscious rats, cimetidine, probenecid, BSP and verapamil significantly increased the AUC of Entecavir by 40.07%, 48.78%, 37.49%, and 54.58%, and reduced the body clearance by 27.14%, 31.69%, 29.79%, and 42.17%, respectively. Then the effects of these inhibitors on the renal clearance of Entecavir in unconscious rats were studied. Coadministration of cimetidine and probenecid increased the steady plasma concentration of Entecavir by 127.61% and 169.46%, reduced the renal clearance by 50.47% and 67.76%, and decreased the excretion ratio by 44.81% and 64.16% compared to initial values. However, the effects of BSP and verapamil were slight. Cimetidine and probenecid also increased the concentration of Entecavir in kidney from 34.00 ± 0.80 ng/mL to 55.19 ± 4.92 ng/mL and 49.92 ± 1.53 ng/mL, while the concentration of Entecavir in kidney from BSP and verapamil groups was 30.96 ± 0.81 ng/mL and 35.72 ± 7.30 ng/mL, respectively. Significance These results suggest that cimetidine and probenecid inhibit the renal excretion of Entecavir in rats, which indicates the most likely involvement of organic anion and cation transporters in the renal excretion of Entecavir.

Deborah Dehertogh - One of the best experts on this subject based on the ideXlab platform.

  • a comparison of Entecavir and lamivudine for hbeag positive chronic hepatitis b
    The New England Journal of Medicine, 2006
    Co-Authors: Tingtsung Chang, You Chen Chao, Adrian Gadano, Jose D Sollano, Zachary Goodman, Robert G Gish, Deborah Dehertogh, Anne Cross, R B Wilber, Richard J Colonno
    Abstract:

    Methods In this phase 3, double-blind trial, we randomly assigned 715 patients with hepatitis B e antigen (HBeAg)–positive chronic hepatitis B who had not previously received a nucleoside analogue to receive either 0.5 mg of Entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks. The primary efficacy end point was histologic improvement (a decrease by at least two points in the Knodell necroinflammatory score, without worsening of fibrosis) at week 48. Secondary end points included a reduction in the serum HBV DNA level, HBeAg loss and seroconversion, and normalization of the alanine aminotransferase level. Results Histologic improvement after 48 weeks occurred in 226 of 314 patients in the Entecavir group (72 percent) and 195 of 314 patients in the lamivudine group (62 percent, P = 0.009). More patients in the Entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay (67 percent vs. 36 percent, P<0.001) and normalization of alanine aminotransferase levels (68 percent vs. 60 percent, P = 0.02). The mean reduction in serum HBV DNA from baseline to week 48 was greater with Entecavir than with lamivudine (6.9 vs. 5.4 log [on a base-10 scale] copies per milliliter, P<0.001). HBeAg seroconversion occurred in 21 percent of Entecavir-treated patients and 18 percent of those treated with lamivudine (P = 0.33). No viral resistance to Entecavir was detected. Safety was similar in the two groups. Conclusions Among patients with HBeAg-positive chronic hepatitis B, the rates of histologic, virologic, and biochemical improvement are significantly higher with Entecavir than with lami vudine. The safety profile of the two agents is similar, and there is no evidence of viral resistance to Entecavir. (ClinicalTrials.gov number, NCT00035633.)

  • Entecavir versus lamivudine for patients with hbeag negative chronic hepatitis b
    The New England Journal of Medicine, 2006
    Co-Authors: Daniel Shouval, Zachary Goodman, Richard J Colonno, Tingtsung Chang, Hugo Cheinquer, Deborah Dehertogh, Anne Cross, R B Wilber, Richard C Zink, Lori Fernandes
    Abstract:

    BACKGROUND Entecavir is a potent and selective antiviral agent that has demonstrated efficacy in phase 2 studies in patients with hepatitis B e antigen (HBeAg)–negative chronic hepatitis B. METHODS In this phase 3, double-blind trial, we randomly assigned 648 patients with HBeAgnegative chronic hepatitis B who had not previously been treated with a nucleoside analogue to receive 0.5 mg of Entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks. The primary efficacy end point was histologic improvement (a decrease by at least two points in the Knodell necroinflammatory score, without worsening of fibrosis). RESULTS Histologic improvement after 48 weeks of treatment occurred in 208 of 296 patients in the Entecavir group who had adequate baseline liver-biopsy specimens that could be evaluated (70 percent), as compared with 174 of 287 such patients in the lamivudine group (61 percent, P = 0.01). More patients in the Entecavir group than in the lamivudine group had undetectable serum hepatitis B virus (HBV) DNA levels according to a polymerase-chain-reaction assay (90 percent vs. 72 percent, P<0.001) and normalization of alanine aminotransferase levels (78 percent vs. 71 percent, P = 0.045). The mean reduction in serum HBV DNA levels from baseline to week 48 was greater with Entecavir than with lamivudine (5.0 vs. 4.5 log [on a base-10 scale] copies per milliliter, P<0.001). There was no evidence of resistance to Entecavir. Safety and adverse-event profiles were similar in the two groups. CONCLUSIONS Among patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue, the rates of histologic improvement, virologic response, and normalization of alanine aminotransferase levels were significantly higher at 48 weeks with Entecavir than with lamivudine. The safety profile of the two agents was similar, and there was no evidence of viral resistance to Entecavir. (ClinicalTrials.gov number, NCT00035789.)

  • Development of Entecavir: Superior Therapy for the Management of Chronic Hepatitis B Viral Infection
    Therapy for Viral Hepatitis and Prevention of Hepatocellular Carcinoma, 2004
    Co-Authors: Deborah Dehertogh, Richard J Colonno, William D. Fiske, Anne Cross
    Abstract:

    Current therapies for chronic hepatitis B virus (HBV) infection are limited by factors such as poor tolerability and viral resistance. The novel and selective HBV antiviral Entecavir (Bristol-Myers Squibb Company; Wallingford, CT) has demonstrated potent activity against HBV and is in phase III clinical development. Oral Entecavir has high bioavailability, shows linear pharmacokinetic properties in several ethnic populations, and is well tolerated. At doses of 0.5 mg to 1.0 mg daily, Entecavir has significantly greater antiviral activity in nucleoside-naive patients, assessed by reduction in HBV viral load, than the currently available therapy lamivudine. Entecavir also shows superior efficacy compared with lamivudine in reducing viremia and normalizing alanine aminotransferase levels in lamivudine-resistant patients. In addition, Entecavir has demonstrated utility in the setting of HBV reinfection occurring in liver transplant recipients. Based on results of phase I and II dose-ranging, safety, and efficacy trials, several multinational phase III trials are currently ongoing. These studies are evaluating the optimal duration of therapy with Entecavir, as well as the durability of response to this novel treatment for chronic HBV infection.

  • Entecavir is superior to lamivudine in reducing hepatitis b virus dna in patients with chronic hepatitis b infection
    Gastroenterology, 2002
    Co-Authors: Ching-lung Lai, Mohamed Rosmawati, Judy Lao, Hans Van Vlierberghe, Frank H Anderson, Neal Thomas, Deborah Dehertogh
    Abstract:

    Abstract Background & Aims: Entecavir is a novel and selective nucleoside analogue with potent activity against hepatitis B virus (HBV). Methods: In a 24-week, double-blind, randomized, multicenter, phase II clinical trial, the safety and efficacy of Entecavir (0.01 mg/day, 0.1 mg/day, or 0.5 mg/day orally) were compared with lamivudine (100 mg/day orally). Patients (n = 169) chronically infected with HBV (hepatitis B e antigen [HBeAg]-positive and -negative) were evaluated for efficacy. Results: Compared with lamivudine, Entecavir reduced HBV DNA by an additional 0.97 log 10 at the 0.1-mg/day dose and an additional 1.28 log 10 at the 0.5-mg/day dose ( P P = 0.008). In both treatment arms, very few patients achieved HBeAg loss and/or seroconversion by week 22. More patients treated with the 0.1-mg/day and 0.5-mg/day doses of Entecavir had normalization of alanine transaminase (ALT) levels at week 22 compared with lamivudine ( P = not significant). Entecavir was well tolerated; most adverse events were mild to moderate, transient, and comparable in all study arms. Conclusions: This study showed that Entecavir has potent antiviral activity against HBV at 0.1-mg/day and 0.5-mg/day doses, both of which were superior to lamivudine in chronically infected HBV patients. GASTROENTEROLOGY 2002;123:1831-1838

Fabien Zoulim - One of the best experts on this subject based on the ideXlab platform.

  • antiviral effect of Entecavir in chronic hepatitis b influence of prior exposure to nucleos t ide analogues
    Journal of Hepatology, 2010
    Co-Authors: Jurrien G P Reijnders, Fabien Zoulim, K Deterding, J Petersen, Teresa Santantonio, Maria Buti, Florian Van Bommel, Bettina E Hansen, Heiner Wedemeyer, Harry L A Janssen
    Abstract:

    Background & Aims Entecavir is a potent inhibitor of viral replication in nucleos(t)ide analogue (NA)-naive chronic hepatitis B patients, but data on the efficacy in NA-experienced subjects are limited. Methods In a multi-center cohort study we investigated 161 chronic hepatitis B patients (34% NA-experienced) treated with Entecavir monotherapy. Results During a median follow-up of 11 (3–23)months, 82 (79%) of 104 NA-naive patients achieved virologic response (VR), defined as HBV DNA p =0.007). Antiviral efficacy was not decreased by prior treatment with lamivudine when lamivudine-resistance had never developed (HR 0.81; 95% CI 0.43–1.52; p =0.52). Prior adefovir therapy without development of adefovir-resistance (HR 0.84; 95% CI 0.43–1.64; p =0.61) and presence of adefovir-resistance (HR 0.86; 95% CI 0.27–2.71; p =0.80) did not influence antiviral response to Entecavir. Switching to a tenofovir-containing treatment regimen resulted in viral load decline in patients with Entecavir-resistance associated mutations. Conclusions Entecavir proved to be efficacious in NA-naive patients. The antiviral efficacy of Entecavir was not influenced by prior treatment with adefovir or presence of adefovir-resistance. Entecavir should not be used in patients with previous lamivudine-resistance, yet it may still be an option in lamivudine-experienced patients in case lamivudine-resistance never developed.

  • Stepwise process for the development of Entecavir resistance in a chronic hepatitis B virus infected patient.
    Journal of Hepatology, 2007
    Co-Authors: Stéphanie Villet, Christian Trepo, Aurélie Ollivet, Christian Pichoud, Luc Barraud, Jean-pierre Villeneuve, Fabien Zoulim
    Abstract:

    BACKGROUND/AIMS: Complex mutants may be selected under sequential anti-VHB pressures. We analyzed the genotypic and phenotypic evolution of the viral quasi-species of a patient who developed resistance to Entecavir following lamivudine breakthrough. METHODS: The polymerase gene was amplified, cloned and sequenced at different time points. Hepatoma cell lines were transfected to compare the replication capacity of HBV mutants and their drug susceptibility. RESULTS: A mixture of lamivudine-resistant HBV strains coexisted following viral breakthrough to lamivudine, all harboring the rtM204V mutation. The rtV173L+L180M+M204V dominant mutant displayed strong lamivudine-resistance and the highest replication capacity. Following the switch to Entecavir, the viral load dropped but the lamivudine-resistant strains continued to be selected. Three years later, the viral load rose again, and a complex mixture of Entecavir-resistant strains, all harboring the lamivudine-resistance signature rtL180M+M204V and the rtS202G mutation were observed. Although the rtL180M+S202G+M204V variant, that prevailed at the end of Entecavir therapy, did not show the highest viral genome replication capacity, it conferred one of the strongest resistance levels to Entecavir. CONCLUSIONS: We report the selection of complex HBV mutants that escaped lamivudine and Entecavir antiviral pressures. Genotypic and phenotypic analysis provided additional information to understand the process of HBV variant selection.

  • Entecavir: A new treatment option for chronic hepatitis B
    Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2006
    Co-Authors: Fabien Zoulim
    Abstract:

    Because of the slow kinetics of viral clearance and the spontaneous genetic variability of hepatitis B virus (HBV), antiviral therapy of chronic hepatitis B remains a clinical challenge. Despite the recent development of lamivudine, adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic HBV infection, there is still a major need for new antiviral compounds. Entecavir, a guanosine analog, has been recently approved in US for the therapy of chronic hepatitis B and its registration is expected soon in Europe. Extensive studies have been performed to characterize its antiviral activity in enzymatic and tissue culture models, as well as in animal models of HBV infection. In clinical trails, Entecavir administration was associated with a significantly more potent viral suppression compared to lamivudine, and a significant advantage in terms of biochemical and histological improvement compared to lamivudine. Entecavir was tolerated as well as lamivudine in these phase III trials. No case of resistance was detected after two years of therapy in nucleoside naive patients. Treatment of patients with lamivudine failure requires a higher dosage of Entecavir and induces a significant decline in viraemia levels. However, 10% of these patients developed Entecavir resistance after two years of therapy. The availability of Entecavir as a new treatment option is providing clincians more choice to keep both viral replication and liver disease under control. This provides new hope for improved treatment concepts for chronic HBV infection.

Yasuji Arase - One of the best experts on this subject based on the ideXlab platform.

  • long term continuous Entecavir therapy in nucleos t ide naive chronic hepatitis b patients
    Journal of Hepatology, 2012
    Co-Authors: Atsushi Ono, Fumitaka Suzuki, Yoshiyuki Suzuki, Yusuke Kawamura, Hitomi Sezaki, Tetsuya Hosaka, Norio Akuta, Masahiro Kobayashi, Satoshi Saitou, Yasuji Arase
    Abstract:

    Background & Aims We determined the antiviral potency and viral resistance rate after 4years of continuous Entecavir treatment in patients with chronic hepatitis B (CHB) infection. Methods The cumulative rates of undetectable hepatitis B virus DNA (HBV DNA; 10 copies/ml), hepatitis B e antigen (HBeAg) seronegativity, seroconversion, alanine aminotransferase (ALT) normalization, and Entecavir signature mutations were calculated in 474 nucleos(t)ide-naive CHB patients (HBeAg-positive: 47%) on continuous Entecavir treatment for 4years. Results Median age was 47years and follow-up period was 2.4years, with 403, 281, 165, and 73 patients followed-up for at least 1, 2, 3, and 4years, respectively. Incremental increases were observed in the rates of undetectable HBV DNA, HBeAg seroclearance and seroconversion, and ALT normalization, reaching 96%, 42%, 38% and 93%, respectively, by the fourth year. In all, 100% and 93% of patients negative and positive for HBeAg, respectively, had undetectable HBV DNA at year 4. Of 165 patients, HBV DNA was detectable in nine patients after 3years. Multivariate analysis identified HBV DNA level (⩽7.6log 10 copies/ml, OR=15.8; 95% CI=43.1–79.9, P=0.001) as an independent predictor of undetectable HBV DNA at year 3. Five patients experienced virological breakthrough including two (0.4%) who developed Entecavir-resistance mutations. Conclusions Continuous treatment of nucleos(t)ide-naive CHB patients with Entecavir over 4years was associated with 96% chance of undetectable HBV DNA and only 0.4% chance of emerging Entecavir-resistant mutations.

  • Efficacy of switching to Entecavir monotherapy in Japanese lamivudine‐pretreated patients
    Journal of gastroenterology and hepatology, 2010
    Co-Authors: Fumitaka Suzuki, Yoshiyuki Suzuki, Yusuke Kawamura, Hiromi Yatsuji, Hitomi Sezaki, Tetsuya Hosaka, Norio Akuta, Yasuji Arase, Miharu Hirakawa, Masahiro Kobayashi
    Abstract:

    Background and Aims:  To assess the efficacy of switching Japanese chronic hepatitis B patients from lamivudine monotherapy to Entecavir 0.5 mg/day. Methods:  A retrospective analysis was conducted on 134 patients switched to Entecavir between September 2006 and February 2008 for 6 months or more. Patients were divided into three groups based on viral load at Entecavir switching point (baseline  5.0 log10 copies/mL). Results:  At baseline, detection of lamivudine-resistant virus was highest in patients with higher hepatitis B virus (HBV) DNA (76% vs 23% in ≥ 2.6 and  3 years, 1–3 years and

  • Efficacy of Entecavir treatment for lamivudine-resistant hepatitis B over 3 years: histological improvement or Entecavir resistance?
    Journal of gastroenterology and hepatology, 2009
    Co-Authors: Yoshiyuki Suzuki, Fumitaka Suzuki, Yusuke Kawamura, Hiromi Yatsuji, Hitomi Sezaki, Tetsuya Hosaka, Norio Akuta, Masahiro Kobayashi, Satoshi Saitoh, Yasuji Arase
    Abstract:

    Background and Aims:  Long-term lamivudine therapy is required for patients with chronic hepatitis B, because hepatitis reappears frequently after it has withdrawn. However, hepatitis B virus (HBV) mutants resistant to lamivudine emerge frequently accompanied by breakthrough hepatitis. Methods:  Effects of Entecavir were evaluated in 19 patients who had developed breakthrough hepatitis during lamivudine therapy for longer than 5 years. This study is a subgroup analysis of a previously reported study. Entecavir, in either 0.5 or 1.0 mg/day doses, was given to 10 and nine patients for 52 weeks, respectively, and then all received 1.0 mg/day Entecavir for an additional 68–92 weeks. Results:  There were no differences in biochemical and virological responses in the two groups of patients with respect to the two different initial doses of Entecavir. Serum levels of alanine aminotransferase were normalized in 17 (90%) patients, and hepatitis B e antigen (HBeAg) disappeared from the serum in two (14%) of the 14 patients who were HBeAg-positive before. Furthermore, a decrease in histological activity index score greater than 2 points was achieved in nine of the 11 (82%) patients in whom annual liver biopsies were performed during 3 years while they received Entecavir. HBV mutants resistant to Entecavir emerged in five of the 19 (26%) patients, and hepatitis flare occurred in two of them (40%). Conclusion:  Entecavir in the long term would be useful for histological improvement of breakthrough hepatitis induced by lamivudine-resistant HBV mutants in patients with chronic hepatitis B. However, the relatively high rate of Entecavir resistance is a concern, and other strategies need to be considered when available.