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Zachary Goodman - One of the best experts on this subject based on the ideXlab platform.

  • efficacy and safety of entecavir in patients with <B>ChronicB> <B>HepatitisB> B and advanced hepatic fiBrosis or cirrhosis
    The American Journal of Gastroenterology, 2008
    Co-Authors: Eugene R Schiff, Zachary Goodman, Harry L A Janssen, Halis Simsek, William M Lee, You Chen Chao, H Sette, Steven Han, Joanna Yang, Helena Brettsmith
    Abstract:

    Efficacy and Safety of Entecavir in Patients With <B>ChronicB> <B>HepatitisB> B and Advanced Hepatic FiBrosis or Cirrhosis

  • entecavir versus lamivudine for patients with hBeag negative <B>ChronicB> <B>HepatitisB> B
    The New England Journal of Medicine, 2006
    Co-Authors: Daniel Shouval, Zachary Goodman, Richard J Colonno, 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 <B>HepatitisB> B e antigen (HBeAg)–negative <B>ChronicB> <B>HepatitisB> B. METHODS In this phase 3, douBle-Blind trial, we randomly assigned 648 patients with HBeAgnegative <B>ChronicB> <B>HepatitisB> 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 <B>HepatitisB> 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 <B>ChronicB> <B>HepatitisB> 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.)

  • long term therapy with adefovir dipivoxil for hBeag negative <B>ChronicB> <B>HepatitisB> B
    The New England Journal of Medicine, 2005
    Co-Authors: Stephanos J Hadziyannis, G Kitis, S Arterburn, Tingtsung Chang, Nicolaos C. Tassopoulos, Jenny E Heathcote, Mario Rizzetto, Zachary Goodman, Patrick Marcellin, S Da-xiong
    Abstract:

    Background Treatment with adefovir dipivoxil for 48 weeks resulted in histologic, virologic, and Biochemical improvement in patients with <B>HepatitisB> B e antigen (HBeAg)–negative <B>ChronicB> <B>HepatitisB> B. We evaluated the effect of continued therapy as compared with cessation of therapy. Methods One hundred eighty-five HBeAg-negative patients with <B>ChronicB> <B>HepatitisB> B were assigned to receive 10 mg of adefovir dipivoxil or placeBo once daily for 48 weeks (ratio, 2:1). After week 48, patients receiving adefovir dipivoxil were again randomly assigned either to receive an additional 48 weeks of the drug or to switch to placeBo. Patients originally assigned to placeBo were switched to adefovir dipivoxil. Patients treated with adefovir dipivoxil during weeks 49 through 96 were suBsequently offered continued therapy. The primary end points were changes in <B>HepatitisB> B virus (HBV) DNA and alanine aminotransferase levels. Results Treatment with adefovir dipivoxil resulted in a median decrease in serum HBV DNA of 3.47 log ...

  • persistence of cccdna during the natural history of <B>ChronicB> <B>HepatitisB> B and decline during adefovir dipivoxil therapy
    Gastroenterology, 2004
    Co-Authors: Bettina Werlelapostolle, Patrick Marcellin, Stephen Locarnini, Christian Trepo, Scott Bowden, K Wursthorn, J Petersen, Zachary Goodman
    Abstract:

    BACKGROUND & AIMS: <B>HepatitisB> B virus (HBV) covalently closed circular DNA (cccDNA) is a unique episomal replicative intermediate responsiBle for persistent infection of hepatocytes. Technical constraints have hampered the direct study of cccDNA maintenance and clearance mechanisms in patients. The aim of this study was to develop a sensitive and specific assay for quantifying cccDNA in Biopsy samples from <B>ChronicB> <B>HepatitisB> B patients during different natural history phases and in patients undergoing antiviral therapy. METHODS: Intrahepatic cccDNA levels were quantified By a specific real-time PCR assay. Ninety-eight liver Biopsy samples from patients in the major phases of the natural history of <B>ChronicB> <B>HepatitisB> B and 32 pairs of samples from patients receiving adefovir dipivoxil (ADV) therapy were assessed. RESULTS: cccDNA was detected, at levels ranging over 3 orders of magnitude, in patients in different phases of the natural history of <B>ChronicB> <B>HepatitisB> B. cccDNA levels were strongly correlated with levels of total intracellular HBV DNA and serum HBV DNA. Forty-eight weeks of ADV therapy resulted in a significant 0.8 log decrease in cccDNA copies/cell. Changes in cccDNA were correlated with a similar reduction in serum HBsAg titer But not with a decrease in the numBer of HBV antigen-positive cells during ADV treatment.CONCLUSIONS: cccDNA persists throughout the natural history of <B>ChronicB> <B>HepatitisB> B, even in patients with serologic evidence of viral clearance. Long-term ADV therapy significantly decreased cccDNA levels By a primarily noncytolytic mechanism.

  • lamivudine as initial treatment for <B>ChronicB> <B>HepatitisB> B in the united states
    The New England Journal of Medicine, 1999
    Co-Authors: Jules L Dienstag, Zachary Goodman, Robert P Perrillo, Eugene R Schiff, Teresa L Wright, Hiewon L Hann, Lynn Crowther, Lynn D Condreay, Mary Woessner, Marc Rubin
    Abstract:

    Background Although the nucleoside analogue lamivudine has shown promise in patients with <B>ChronicB> <B>HepatitisB> B, long-term data on patients from the United States are lacking. Methods We randomly assigned previously untreated patients with <B>ChronicB> <B>HepatitisB> B to receive either 100 mg of oral lamivudine or placeBo daily for 52 weeks. We then followed them for an additional 16 weeks to evaluate post-treatment safety and the duraBility of responses. The primary end point with respect to efficacy was a reduction of at least 2 points in the score on the Histologic Activity Index. On this scale, scores can range from 0 (normal) to 22 (most severe aBnormalities). Results Of the 143 randomized patients, 137 were included in the efficacy analysis: 66 in the lamivudine group and 71 in the placeBo group. The other six patients were excluded at the Base-line visit Because of the aBsence of a documented history of <B>HepatitisB> B surface antigen for at least six months. After 52 weeks of treatment, lamivudine recipients wer...

George V. Papatheodoridis - One of the best experts on this subject based on the ideXlab platform.

  • telBivudine improves renal function in patients with <B>ChronicB> <B>HepatitisB> B
    Gastroenterology, 2014
    Co-Authors: Edward Gane, Adrian M. Di Bisceglie, George V. Papatheodoridis, Yuming Wang, Yunfan Liaw, Seng Gee Lim, C L Lai, J Rasenack, Gilbert Deray, Maria Buti
    Abstract:

    Background & Aims There is a close relationship Between <B>ChronicB> <B>HepatitisB> B virus infection and <B>ChronicB> 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 <B>ChronicB> <B>HepatitisB> B virus infection. Methods We used serum creatinine-Based equations (ie, Cockcroft-Gault, Modification of Diet in Renal Disease, and <B>ChronicB> Kidney Disease Epidemiology CollaBoration) to estimate GFR (eGFR) in adults with <B>ChronicB> <B>HepatitisB> 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 <B>ChronicB> 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.

  • incidence of hepatocellular carcinoma in <B>ChronicB> <B>HepatitisB> B patients receiving nucleos t ide therapy a systematic review
    Journal of Hepatology, 2010
    Co-Authors: George V. Papatheodoridis, P Lampertico, Spilios Manolakopoulos
    Abstract:

    Background & Aims: <B>ChronicB> <B>HepatitisB> B patients are at increased risk for hepatocellular carcinoma (HCC). The effect of medium-term nucleos(t)ide analogue therapy on HCC incidence is unclear; therefore, we systematically reviewed all the data on HCC incidence from studies in <B>ChronicB> <B>HepatitisB> B patients treated with nucleos(t)ide analogues. Methods: We performed a literature search to identify studies with <B>ChronicB> <B>HepatitisB> B patients treated with nucleos(t)ide analogues for ⩾24months. Results: Twenty-one studies including 3881 treated and 534 untreated patients met our inclusion criteria. HCC was diagnosed in 2.8% and 6.4% of treated and untreated patients, respectively, during a 46 (32–108) month period ( p =0.003), in 10.8% and 0.5% of nucleos(t)ide naive patients with and without cirrhosis ( p p p p =0.466). Conclusions: <B>ChronicB> <B>HepatitisB> B patients receiving medium-term nucleos(t)ide analogue therapy had a significantly lower incidence of HCC compared to untreated patients But treatment does not completely eliminate the risk of HCC. Among the treated patients, cirrhosis, HBeAg negative at Baseline and failure to remain in virological remission were associated with an increased risk of HCC.

  • <B>HepatitisB> B e antigen negative <B>ChronicB> <B>HepatitisB> B natural history and treatment
    Seminars in Liver Disease, 2006
    Co-Authors: Stephanos J Hadziyannis, George V. Papatheodoridis
    Abstract:

    <B>HepatitisB> B e antigen (HBeAg)-negative <B>ChronicB> <B>HepatitisB> B evolves in the natural history of <B>ChronicB> <B>HepatitisB> B virus (HBV) infection linked with selection of nonproducing HBeAg But replication-competent HBV mutants, and may have a potentially severe and progressive course. Effective suppression of HBV replication is the main therapeutic target. Sustained off-therapy responses are rare with treatment of finite duration, except perhaps for interferon-Based therapies, which induce such responses in a sizeaBle, yet small proportion of patients. Eventually, the majority of patients will Be treated with long-term oral antiviral therapy, which improves patients' outcome But is associated with progressively increasing rates of viral resistance. The long-term resistance profile of adefovir is significantly Better than that of lamivudine (LMV), whereas data for entecavir currently are limited to 2 years, with resistance developing in LMV-resistant But not in treatment-naive patients. ComBination therapy with adefovir added to LMV in LMV-resistant patients is extremely effective; cases of adefovir-resistance have not Been reported to date.

  • nucleoside analogues for <B>ChronicB> <B>HepatitisB> B antiviral efficacy and viral resistance
    The American Journal of Gastroenterology, 2002
    Co-Authors: George V. Papatheodoridis, Evangelini Dimou, Vasilios Papadimitropoulos
    Abstract:

    Nucleoside analogues have Been recently introduced in the management of <B>ChronicB> <B>HepatitisB> B virus (HBV) infection. They mainly act By inhiBition of HBV polymerase activity resulting in decrease of viral replication. They are administered orally, and most of them have an excellent tolerance and safety profile. Lamivudine is the only nucleoside analogue licensed for <B>ChronicB> <B>HepatitisB> B. It has potent activity against HBV, and a 12-month course achieves clearance of <B>HepatitisB> B e antigen (HBeAg) in 20-30% of HBeAg-positive patients and Both Biochemical and virological remission in more than 65-70% of HBeAg-negative <B>ChronicB> <B>HepatitisB> B patients. Famciclovir and ganciclovir are less effective, whereas other nucleoside or nucleotide analogues, such as adefovir, entecavir, and emtricitaBine, are currently under evaluation. Prolonged effective antiviral therapy is required for eradication of <B>ChronicB> HBV infection, But long-term treatment with nucleoside analogues has Been found to Be associated with progressively increasing rates of viral resistance Because of emergence of resistant HBV mutant strains. Virological Breakthroughs usually develop after the first 6 months of lamivudine monotherapy, and their rate ranges Between 15% and 30% at 12 months and exceeds 50% after 3 yr of therapy. Resistant HBV mutant strains harBor point mutations in the HBV polymerase gene and predominantly in the well-conserved YMDD motif. Although resistant HBV strains may have impaired replication capacity compared with the wild HBV, their clinical significance has not Been completely clarified yet. No significant Biochemical or clinical event may develop in some cases, whereas severe Biochemical Breakthroughs with or without deterioration of liver function may develop in others. To date, there is no proven effective therapy for the resistant HBV mutant strains, although adefovir and entecavir seem to Be interesting candidates.

Patrick Marcellin - One of the best experts on this subject based on the ideXlab platform.

  • three year efficacy and safety of tenofovir disoproxil fumarate treatment for <B>ChronicB> <B>HepatitisB> B
    Gastroenterology, 2011
    Co-Authors: Jenny E Heathcote, Edward Gane, Patrick Marcellin, Maria Buti, Z Krastev, George Germanidis, Robert Flisiak, Kelly Kaita, Michael P Manns, Iskren Kotzev
    Abstract:

    Background & Aims Tenofovir disoproxil fumarate (TDF), a nucleotide analogue and potent inhiBitor of <B>HepatitisB> B virus (HBV) polymerase, showed superior efficacy to adefovir dipivoxil in treatment of <B>ChronicB> <B>HepatitisB> B through 48 weeks. We evaluated long-term efficacy and safety of TDF monotherapy in patients with <B>ChronicB> <B>HepatitisB> B who were positive or negative for <B>HepatitisB> B e antigen (HBeAg + or HBeAg − ). Methods After 48 weeks of douBle-Blind comparison of TDF to adefovir dipivoxil, patients who underwent liver Biopsy were eligiBle to continue the study on open-laBel TDF for 7 additional years; data presented were collected up to 3 years (week 144) from 85% of participants. Primary efficacy end points at week 144 included levels of HBV DNA and alanine aminotransferase, development of resistance mutations, and presence of HBeAg or <B>HepatitisB> B surface antigen (HBsAg). Results At week 144, 87% of HBeAg − and 72% of HBeAg + patients treated with TDF had levels of HBV DNA − and 71% of the HBeAg + patients had levels of HBV DNA + patients lost HBsAg. TDF maintained a favoraBle safety profile for up to 3 years. Conclusions TDF was safe and effective in the long-term management of HBeAg + and HBeAg − patients with <B>ChronicB> <B>HepatitisB> B.

  • characteristics of patients with <B>ChronicB> <B>HepatitisB> B in france predominant frequency of hBe antigen negative cases
    Journal of Hepatology, 2006
    Co-Authors: Jeanpierre Zarski, Patrick Marcellin, Vincent Leroy, Christian Trepo, Didier Samuel, Nathalie Gannecarrie, Karl Barange, V Canva, M Doffoel, Paul Cales
    Abstract:

    Background/Aims An increasing prevalence of HBe antigen (HBeAg) negative <B>ChronicB> <B>HepatitisB> B has Been recently reported in many countries. The aim of this study was to analyze the frequency and the characteristics of HBeAg-negative as compared with HBeAg-positive <B>ChronicB> <B>HepatitisB> B in France. Methods Eight hundred and sixty-five patients with histologically proven <B>ChronicB> <B>HepatitisB> B seen in 26 University centers were included. The proportion with HBeAg-negative <B>ChronicB> <B>HepatitisB> B was 72% and higher in patients Born in Africa, Middle East, Eastern, and Southern Europe than in those of French or Asian origin. HBeAg-negative patients were significantly older ( p p p p p 10 copies/mL were independently associated with cirrhosis. Results HBeAg-negative <B>ChronicB> <B>HepatitisB> B is predominant in France. This oBservation is important for an optimized clinical management and future therapeutic trials in <B>ChronicB> <B>HepatitisB> B.

  • long term therapy with adefovir dipivoxil for hBeag negative <B>ChronicB> <B>HepatitisB> B
    The New England Journal of Medicine, 2005
    Co-Authors: Stephanos J Hadziyannis, G Kitis, S Arterburn, Tingtsung Chang, Nicolaos C. Tassopoulos, Jenny E Heathcote, Mario Rizzetto, Zachary Goodman, Patrick Marcellin, S Da-xiong
    Abstract:

    Background Treatment with adefovir dipivoxil for 48 weeks resulted in histologic, virologic, and Biochemical improvement in patients with <B>HepatitisB> B e antigen (HBeAg)–negative <B>ChronicB> <B>HepatitisB> B. We evaluated the effect of continued therapy as compared with cessation of therapy. Methods One hundred eighty-five HBeAg-negative patients with <B>ChronicB> <B>HepatitisB> B were assigned to receive 10 mg of adefovir dipivoxil or placeBo once daily for 48 weeks (ratio, 2:1). After week 48, patients receiving adefovir dipivoxil were again randomly assigned either to receive an additional 48 weeks of the drug or to switch to placeBo. Patients originally assigned to placeBo were switched to adefovir dipivoxil. Patients treated with adefovir dipivoxil during weeks 49 through 96 were suBsequently offered continued therapy. The primary end points were changes in <B>HepatitisB> B virus (HBV) DNA and alanine aminotransferase levels. Results Treatment with adefovir dipivoxil resulted in a median decrease in serum HBV DNA of 3.47 log ...

  • peginterferon alfa 2a lamivudine and the comBination for hBeag positive <B>ChronicB> <B>HepatitisB> B
    The New England Journal of Medicine, 2005
    Co-Authors: Teerha Piratvisuth, Satawat Thongsawat, Graham Cooksley, W.c. Chow, Wen Yu Chang, Seung Woon Paik, Edward Gane, Patrick Marcellin, Michael Fried, Thomas Berg
    Abstract:

    Background: Current treatments for <B>ChronicB> <B>HepatitisB> B are suBoptimal. In the search for improved therapies, we compared the efficacy and safety of pegylated interferon alfa plus lamivudine, pegylated interferon alfa without lamivudine, and lamivudine alone for the treatment of <B>HepatitisB> B e antigen (HBeAg)–positive <B>ChronicB> <B>HepatitisB> B. Methods: A total of 814 patients with HBeAg-positive <B>ChronicB> <B>HepatitisB> B received either peginterferon alfa-2a (180 µg once weekly) plus oral placeBo, peginterferon alfa-2a plus lamivudine (100 mg daily), or lamivudine alone. The majority of patients in the study were Asian (87 percent). Most patients were infected with <B>HepatitisB> B virus (HBV) genotype B or C. Patients were treated for 48 weeks and followed for an additional 24 weeks. Results: After 24 weeks of follow-up, significantly more patients who received peginterferon alfa-2a monotherapy or peginterferon alfa-2a plus lamivudine than those who received lamivudine monotherapy had HBeAg seroconversion (32 percent vs. 19 percent [P<0.001] and 27 percent vs. 19 percent [P=0.02], respectively) or HBV DNA levels Below 100,000 copies per milliliter (32 percent vs. 22 percent [P=0.01] and 34 percent vs. 22 percent [P=0.003], respectively). Sixteen patients receiving peginterferon alfa-2a (alone or in comBination) had <B>HepatitisB> B surface antigen (HBsAg) seroconversion, as compared with 0 in the group receiving lamivudine alone (P=0.001). The most common adverse events were those known to occur with therapies Based on interferon alfa. Serious adverse events occurred in 4 percent, 6 percent, and 2 percent of patients receiving peginterferon alfa-2a monotherapy, comBination therapy, and lamivudine monotherapy, respectively. Two patients receiving lamivudine monotherapy had irreversiBle liver failure after the cessation of treatment — one underwent liver transplantation, and the other died. Conclusions: In patients with HBeAg-positive <B>ChronicB> <B>HepatitisB> B, peginterferon alfa-2a offers superior efficacy over lamivudine, on the Basis of HBeAg seroconversion, HBV DNA suppression, and HBsAg seroconversion.

  • persistence of cccdna during the natural history of <B>ChronicB> <B>HepatitisB> B and decline during adefovir dipivoxil therapy
    Gastroenterology, 2004
    Co-Authors: Bettina Werlelapostolle, Patrick Marcellin, Stephen Locarnini, Christian Trepo, Scott Bowden, K Wursthorn, J Petersen, Zachary Goodman
    Abstract:

    BACKGROUND & AIMS: <B>HepatitisB> B virus (HBV) covalently closed circular DNA (cccDNA) is a unique episomal replicative intermediate responsiBle for persistent infection of hepatocytes. Technical constraints have hampered the direct study of cccDNA maintenance and clearance mechanisms in patients. The aim of this study was to develop a sensitive and specific assay for quantifying cccDNA in Biopsy samples from <B>ChronicB> <B>HepatitisB> B patients during different natural history phases and in patients undergoing antiviral therapy. METHODS: Intrahepatic cccDNA levels were quantified By a specific real-time PCR assay. Ninety-eight liver Biopsy samples from patients in the major phases of the natural history of <B>ChronicB> <B>HepatitisB> B and 32 pairs of samples from patients receiving adefovir dipivoxil (ADV) therapy were assessed. RESULTS: cccDNA was detected, at levels ranging over 3 orders of magnitude, in patients in different phases of the natural history of <B>ChronicB> <B>HepatitisB> B. cccDNA levels were strongly correlated with levels of total intracellular HBV DNA and serum HBV DNA. Forty-eight weeks of ADV therapy resulted in a significant 0.8 log decrease in cccDNA copies/cell. Changes in cccDNA were correlated with a similar reduction in serum HBsAg titer But not with a decrease in the numBer of HBV antigen-positive cells during ADV treatment.CONCLUSIONS: cccDNA persists throughout the natural history of <B>ChronicB> <B>HepatitisB> B, even in patients with serologic evidence of viral clearance. Long-term ADV therapy significantly decreased cccDNA levels By a primarily noncytolytic mechanism.

Manfung Yuen - One of the best experts on this subject based on the ideXlab platform.

Chinglung Lai - One of the best experts on this subject based on the ideXlab platform.

  • Body mass index is associated with fiBrosis regression during long term nucleoside analogue therapy in <B>ChronicB> <B>HepatitisB> B
    Alimentary Pharmacology & Therapeutics, 2016
    Co-Authors: W K Seto, Chinglung Lai, Ka Shing Cheung, James Fung, Lungyi Mak, R W Hui, K S H Liu, M F Yuen
    Abstract:

    SummaryBackground Factors influencing changes in liver stiffness measurements during long-term nucleoside analogue therapy for <B>ChronicB> <B>HepatitisB> 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 <B>ChronicB> <B>HepatitisB> 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 <B>ChronicB> <B>HepatitisB> B.

  • acute on <B>ChronicB> liver failure in <B>ChronicB> <B>HepatitisB> B
    Journal of Gastroenterology and Hepatology, 2012
    Co-Authors: Waikay Seto, Chinglung Lai, Manfung Yuen
    Abstract:

    Acute-on-<B>ChronicB> liver failure (ACLF) in <B>ChronicB> <B>HepatitisB> B (CHB) is most commonly caused By acute severe exacerBation of CHB. The pathophysiology of ACLF in CHB is still poorly understood. Despite the identification of important predisposing factors and prognostic markers, ACLF in CHB remains a disease associated with high mortality. The majority of studies using nucleoside analog therapy did not show any significant improvement in survival, although larger prospective studies are needed. Liver transplantation is the definitive treatment for ACLF in CHB. The challenge ahead would Be prognosticating cases with favoraBle or unfavoraBle outcomes in order to streamline patients for early transplantation or for medical therapy.

  • quantitative <B>HepatitisB> B surface antigen levels in patients with <B>ChronicB> <B>HepatitisB> B after 2 years of entecavir treatment
    The American Journal of Gastroenterology, 2011
    Co-Authors: James Fung, Chinglung Lai, Waikay Seto, John Young, Danny Kaho Wong, John Yuen, Manfung Yuen
    Abstract:

    Quantitative <B>HepatitisB> B Surface Antigen Levels in Patients With <B>ChronicB> <B>HepatitisB> B After 2 Years of Entecavir Treatment

  • the duration of lamivudine therapy for <B>ChronicB> <B>HepatitisB> B cessation vs continuation of treatment after hBeag seroconversion
    The American Journal of Gastroenterology, 2009
    Co-Authors: James Fung, Chinglung Lai, Danny Kaho Wong, John Yuen, Yasuhito Tanaka, Masashi Mizokami, Manfung Yuen
    Abstract:

    The Duration of Lamivudine Therapy for <B>ChronicB> <B>HepatitisB> B: Cessation vs. Continuation of Treatment After HBeAg Seroconversion

  • telBivudine versus lamivudine in patients with <B>ChronicB> <B>HepatitisB> B
    The New England Journal of Medicine, 2007
    Co-Authors: Chinglung Lai, Jenny E Heathcote, Satawat Thongsawat, Edward Gane, Chaowei Hsu, Yicheng Chen, Yuming Wang, Yunfan Liaw, J Rasenack, Natalie Bzowej
    Abstract:

    Background Reducing <B>HepatitisB> B virus (HBV) replication to minimal levels is emerging as a key therapeutic goal for <B>ChronicB> <B>HepatitisB> B. Methods In this douBle-Blind, phase 3 trial, 1370 patients with <B>ChronicB> <B>HepatitisB> B were randomly assigned to receive 600 mg of telBivudine or 100 mg of lamivudine once daily. The primary efficacy end point was noninferiority of telBivudine to lamivudine for therapeutic response (i.e., a reduction in serum HBV DNA levels to fewer than 5 log10 copies per milliliter, along with loss of <B>HepatitisB> B e antigen [HBeAg] or normalization of alanine aminotransferase levels). Secondary efficacy measures included histologic response, changes in serum HBV DNA levels, and HBeAg responses. Results At week 52, a significantly higher proportion of HBeAg-positive patients receiving telBivudine than of those receiving lamivudine had a therapeutic response (75.3% vs. 67.0%, P=0.005) or a histologic response (64.7% vs. 56.3%, P=0.01); telBivudine also was not inferior to lamivudine for thes...