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

Robert P Perrillo - One of the best experts on this subject based on the ideXlab platform.

Stephanos J Hadziyannis - One of the best experts on this subject based on the ideXlab platform.

  • <B>HepatitisB> B e antigen negative chronic <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 chronic <B>HepatitisB> B evolves in the natural history of chronic <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.

  • significance of <B>HepatitisB> B viremia levels determined By a quantitative polymerase chain reaction assay in patients with <B>HepatitisB> B e antigen negative chronic <B>HepatitisB> B virus infection
    The American Journal of Gastroenterology, 2003
    Co-Authors: Emanuel K Manesis, George V. Papatheodoridis, Vasilios Sevastianos, Evangelos Cholongitas, Christos Papaioannou, Stephanos J Hadziyannis
    Abstract:

    OBJECTIVES: In <B>HepatitisB> B e antigen (HBeAg)-negative chronic <B>HepatitisB> B virus (HBV) infection, the clinical relevance of low viremia levels remains unclear. We evaluated the clinical significance of a single Baseline serum HBV DNA measurement By a quantitative polymerase chain reaction (PCR) assay in this setting. METHODS: In total, 196 patients with HBeAg-negative chronic HBV infection (62 inactive carriers, 134 with chronic <B>HepatitisB> B) were studied. ALT activity was normal at Baseline in 25/134 HBeAg-negative chronic <B>HepatitisB> B patients (18.7%), whereas it remained normal throughout follow-up in all inactive carriers. RESULTS: HBV DNA was 0.200 could correctly classify only 87.2% and 82.1% of patients, respectively. A comBined HBV DNA and IgM anti-HBc index performed Better By correctly classifying 94.4% of cases. CONCLUSIONS: Serum HBV DNA levels evaluated By sensitive quantitative PCR assays can Be used for differentiation Between HBeAg-negative chronic <B>HepatitisB> B and inactive <B>HepatitisB> B surface antigen carrier state, But the cut-off level should Be set at approximately 30,000 copies/ml and certainly lower than the recently suggested level of 100,000 copies/ml.

  • adefovir dipivoxil for the treatment of <B>HepatitisB> B e antigen negative chronic <B>HepatitisB> B
    The New England Journal of Medicine, 2003
    Co-Authors: Stephanos J Hadziyannis, Michael Wulfsohn, G Kitis, Tingtsung Chang, Nicolaos C. Tassopoulos, Jenny E Heathcote, Mario Rizzetto, Zachary Goodman, Patrick Marcellin, S Da-xiong
    Abstract:

    Background Adefovir dipivoxil, a nucleotide analogue, demonstrated clinically significant antiviral activity in patients with chronic <B>HepatitisB> B in phase 1 and 2 clinical trials. Methods We randomly assigned 185 patients with chronic <B>HepatitisB> B who were negative for <B>HepatitisB> B e antigen (HBeAg) to receive either 10 mg of adefovir dipivoxil or placeBo once daily for 48 weeks in a 2:1 ratio and a douBle-Blind manner. The primary end point was histologic improvement. Results At week 48, 64 percent of patients who had Base-line liver-Biopsy specimens availaBle in the adefovir dipivoxil group had improvement in histologic liver aBnormalities (77 of 121), as compared with 33 percent of patients in the placeBo group (19 of 57, P<0.001). Serum <B>HepatitisB> B virus (HBV) DNA levels were reduced to fewer than 400 copies per milliliter in 51 percent of patients in the adefovir dipivoxil group (63 of 123) and in 0 percent of those in the placeBo group (0 of 61, P<0.001). The median decrease in log-transformed HBV DNA...

Jiahorng Kao - One of the best experts on this subject based on the ideXlab platform.

  • quantitative <B>HepatitisB> B core antiBody levels in the natural history of <B>HepatitisB> B virus infection
    Clinical Microbiology and Infection, 2015
    Co-Authors: L W Song, T Y Zhang, Xiaodong Cheng, Hungchih Yang, Quan Yuan, P G Liu, Chunjen Liu, Xiaoke Hao, Jing Zhang, Jiahorng Kao
    Abstract:

    We previously demonstrated that pretreatment quantitative anti-<B>HepatitisB> B core protein (qAnti-HBc) levels can predict the treatment response for Both interferon and nucleoside analogue therapy, But the characteristics of qAnti-HBc during chronic <B>HepatitisB> B virus (HBV) infection remain poorly understood. To understand this issue, the qAnti-HBc levels were evaluated in individuals with past HBV infection, occult HBV infection and chronic HBV infection in the immune tolerance phase, immune clearance phase, low-replicative phase and <B>HepatitisB> B e antigen (HBeAg)-negative <B>HepatitisB> phase. Individuals with <B>HepatitisB> B surface antigen (n = 598, 3.74 ± 0.90 log10 IU/mL) had significantly higher (p < 0.001, approximately 1000-fold) serum qAnti-HBc levels than those who had occult HBV, and serum qAnti-HBc levels were significantly higher in the occult HBV group than in the past HBV infection group (p < 0.001). qAnti-HBc levels were positively correlated with alanine aminotransferase levels (R = 0.663, p < 0.001), and suBjects with an aBnormal alanine aminotransferase level had a higher qAnti-HBc level (p < 0.001). Serum qAnti-HBc level varied in different phases of HBV infection, as determined By host immune status. Serum qAnti-HBc level is strongly associated with <B>HepatitisB> activity in suBjects with chronic HBV infection.

  • <B>HepatitisB> B e antigen seroconversion a critical event in chronic <B>HepatitisB> B virus infection
    Digestive Diseases and Sciences, 2010
    Co-Authors: Yun Fan Liaw, Jiahorng Kao, George K K Lau, Edward Gane
    Abstract:

    Background Replication of <B>HepatitisB> B virus (HBV) is the primary driver of disease progression and clinical outcomes in patients with chronic <B>HepatitisB> B (CHB), But other factors, such as <B>HepatitisB> B e antigen (HBeAg) status, also influence disease course. The importance of HBeAg seroconversion is underscored By current CHB treatment guidelines that recommend limiting the duration of antiviral therapy in HBeAg-positive patients who achieve seroconversion.

  • <B>HepatitisB> B viral factors and clinical outcomes of chronic <B>HepatitisB> B
    Journal of Biomedical Science, 2008
    Co-Authors: Chihlin Lin, Jiahorng Kao
    Abstract:

    <B>HepatitisB> B virus (HBV) infection is an important health proBlem and the major cause of chronic <B>HepatitisB>, cirrhosis as well as hepatocellular carcinoma (HCC) worldwide. The natural history of chronic HBV infection can Be divided into 4 dynamic phases in HBV carriers who acquire the virus early in life. In general, the frequency and severity of <B>HepatitisB> flares in the immune clearance or reactivation phase predict disease progression in HBV carriers, and early HBeAg seroconversion typically confers a favoraBle outcome. In contrast, late or aBsent HBeAg seroconversion after multiple <B>HepatitisB> flares accelerates the progression of chronic <B>HepatitisB> to cirrhosis. Recently, several <B>HepatitisB> B viral factors predictive of clinical outcomes have Been identified. For example, serum HBV DNA level at enrollment is the Best predictor of adverse outcomes (cirrhosis, HCC and death from liver disease) in adults with chronic HBV infection. In addition, HBV genotype C, Basal core promoter (BCP) mutant and pre-S deletion mutant are associated with increased risk of HCC development. In conclusion, <B>HepatitisB> B viral factors such as serum HBV DNA level, genotype and mutants have already Been clarified to influence disease progression of chronic <B>HepatitisB> B. Further studies are needed to investigate the pathogenic mechanism of each viral factor.

  • higher cut off index value of immunogloBulin m antiBody to <B>HepatitisB> B core antigen in taiwanese patients with <B>HepatitisB> B
    Journal of Gastroenterology and Hepatology, 2006
    Co-Authors: Yiwen Huang, Peijer Chen, Jiahorng Kao, Ming Yang Lai, Chihlin Lin, Dingshinn Chen
    Abstract:

    Background:  The cut-off index value of immunogloBulin M (IgM) antiBody to <B>HepatitisB> B core antigen (anti-HBc; AxSYM CORE-M, ABBott) for diagnosing acute <B>HepatitisB> B is 1.2. A high false-positive rate of IgM anti-HBc was oBserved in acute flare-ups of chronic <B>HepatitisB> B in Taiwanese patients. Thus the purpose of the present paper was to study the optimal index value of IgM anti-HBc in Taiwanese suBjects. Methods:  The peak index values of 42 IgM anti-HBc-positive patients were collected. There were 20 acute <B>HepatitisB> B patients and 22 patients with chronic <B>HepatitisB> B with acute flare. The Biochemical, virological, and serological data were oBtained. Results:  There were significant differences in mean age (36 vs 47 years, P = 0.01), serum alanine aminotransferase level (2042 U/L vs 1193 U/L, P = 0.02) and peak index value of IgM anti-HBc (2.9 vs 1.5, P  1.2. The optimal cut-off index value to differentiate acute <B>HepatitisB> B from chronic <B>HepatitisB> B with acute flare was 2.4–2.5, with a sensitivity of 90% and specificity of 90%. Conclusions:  The cut-off index value of IgM anti-HBc to differentiate acute <B>HepatitisB> B from chronic <B>HepatitisB> B with acute flare among Taiwanese patients should Be set at 2.4–2.5 instead of 0.8–1.2.

  • Basal core promoter mutant of <B>HepatitisB> B virus and progression of liver disease in <B>HepatitisB> B e antigen negative chronic <B>HepatitisB> B
    Liver International, 2005
    Co-Authors: Chihlin Lin, Peijer Chen, Ming Yang Lai, Dingshinn Chen, Liying Liao, Chaurshine Wang, Jiahorng Kao
    Abstract:

    Background/Aims: The long-term outcomes in <B>HepatitisB> B e antigen (HBeAg)-negative chronic <B>HepatitisB> B are distinct from those in HBeAg-positive chronic <B>HepatitisB>. However, the molecular virological factors that contriBute to the progression of liver disease in this special clinical setting remain largely unknown. We thus investigated the association of <B>HepatitisB> B virus (HBV) genotypes as well as precore/Basal core-promoter mutations with the clinical and virological characteristics of patients with HBeAg-negative chronic <B>HepatitisB> B in Taiwan. Methods: HBV genotypes and sequences of precore and Basal core-promoter regions of the HBV genome were determined in 174 HBeAg-negative chronic HBV infection patients including 62 inactive carriers and 112 with different stages of liver disease. Results: HBV carriers with older age (>50 years) (odds ratio, 9.09; 95% confidence interval (CI), 3.22–25, P<0.001) and Basal core-promoter mutant of HBV (odds ratio, 4.12; 95% CI, 1.41–12.03, P=0.01) were associated with the development of liver cirrhosis and hepatocellular carcinoma (HCC). The gender-related risk factors associated with the development of liver cirrhosis and HCC were further analyzed, and Basal core-promoter mutant was only associated with the development of liver cirrhosis and HCC in male carriers (odds ratio, 4.35; 95% CI, 1.30–14.52, P=0.02). Conclusions: The risk of development of liver cirrhosis and HCC is significantly increased in patients with advanced age as well as with Basal core-promoter mutant of HBV. In addition, Basal core-promoter mutant might contriBute to the gender difference of the progression of liver disease in HBeAg-negative chronic <B>HepatitisB> B in Taiwan.

Dingshinn Chen - One of the best experts on this subject based on the ideXlab platform.

  • quantitative <B>HepatitisB> B core antiBody levels in the natural history of <B>HepatitisB> B virus infection
    Clinical Microbiology and Infection, 2015
    Co-Authors: L W Song, Dingshinn Chen, T Y Zhang, Xiaodong Cheng, H L Wu, Hungchih Yang, Quan Yuan, Jun Zhang, Peijer Chen
    Abstract:

    ABstract We previously demonstrated that pretreatment quantitative anti–<B>HepatitisB> B core protein (qAnti-HBc) levels can predict the treatment response for Both interferon and nucleoside analogue therapy, But the characteristics of qAnti-HBc during chronic <B>HepatitisB> B virus (HBV) infection remain poorly understood. To understand this issue, the qAnti-HBc levels were evaluated in individuals with past HBV infection, occult HBV infection and chronic HBV infection in the immune tolerance phase, immune clearance phase, low-replicative phase and <B>HepatitisB> B e antigen (HBeAg)-negative <B>HepatitisB> phase. Individuals with <B>HepatitisB> B surface antigen ( n  = 598, 3.74 ± 0.90 log 10 IU/mL) had significantly higher (p  R  = 0.663, p

  • higher cut off index value of immunogloBulin m antiBody to <B>HepatitisB> B core antigen in taiwanese patients with <B>HepatitisB> B
    Journal of Gastroenterology and Hepatology, 2006
    Co-Authors: Yiwen Huang, Peijer Chen, Jiahorng Kao, Ming Yang Lai, Chihlin Lin, Dingshinn Chen
    Abstract:

    Background:  The cut-off index value of immunogloBulin M (IgM) antiBody to <B>HepatitisB> B core antigen (anti-HBc; AxSYM CORE-M, ABBott) for diagnosing acute <B>HepatitisB> B is 1.2. A high false-positive rate of IgM anti-HBc was oBserved in acute flare-ups of chronic <B>HepatitisB> B in Taiwanese patients. Thus the purpose of the present paper was to study the optimal index value of IgM anti-HBc in Taiwanese suBjects. Methods:  The peak index values of 42 IgM anti-HBc-positive patients were collected. There were 20 acute <B>HepatitisB> B patients and 22 patients with chronic <B>HepatitisB> B with acute flare. The Biochemical, virological, and serological data were oBtained. Results:  There were significant differences in mean age (36 vs 47 years, P = 0.01), serum alanine aminotransferase level (2042 U/L vs 1193 U/L, P = 0.02) and peak index value of IgM anti-HBc (2.9 vs 1.5, P  1.2. The optimal cut-off index value to differentiate acute <B>HepatitisB> B from chronic <B>HepatitisB> B with acute flare was 2.4–2.5, with a sensitivity of 90% and specificity of 90%. Conclusions:  The cut-off index value of IgM anti-HBc to differentiate acute <B>HepatitisB> B from chronic <B>HepatitisB> B with acute flare among Taiwanese patients should Be set at 2.4–2.5 instead of 0.8–1.2.

  • Basal core promoter mutant of <B>HepatitisB> B virus and progression of liver disease in <B>HepatitisB> B e antigen negative chronic <B>HepatitisB> B
    Liver International, 2005
    Co-Authors: Chihlin Lin, Peijer Chen, Ming Yang Lai, Dingshinn Chen, Liying Liao, Chaurshine Wang, Jiahorng Kao
    Abstract:

    Background/Aims: The long-term outcomes in <B>HepatitisB> B e antigen (HBeAg)-negative chronic <B>HepatitisB> B are distinct from those in HBeAg-positive chronic <B>HepatitisB>. However, the molecular virological factors that contriBute to the progression of liver disease in this special clinical setting remain largely unknown. We thus investigated the association of <B>HepatitisB> B virus (HBV) genotypes as well as precore/Basal core-promoter mutations with the clinical and virological characteristics of patients with HBeAg-negative chronic <B>HepatitisB> B in Taiwan. Methods: HBV genotypes and sequences of precore and Basal core-promoter regions of the HBV genome were determined in 174 HBeAg-negative chronic HBV infection patients including 62 inactive carriers and 112 with different stages of liver disease. Results: HBV carriers with older age (>50 years) (odds ratio, 9.09; 95% confidence interval (CI), 3.22–25, P<0.001) and Basal core-promoter mutant of HBV (odds ratio, 4.12; 95% CI, 1.41–12.03, P=0.01) were associated with the development of liver cirrhosis and hepatocellular carcinoma (HCC). The gender-related risk factors associated with the development of liver cirrhosis and HCC were further analyzed, and Basal core-promoter mutant was only associated with the development of liver cirrhosis and HCC in male carriers (odds ratio, 4.35; 95% CI, 1.30–14.52, P=0.02). Conclusions: The risk of development of liver cirrhosis and HCC is significantly increased in patients with advanced age as well as with Basal core-promoter mutant of HBV. In addition, Basal core-promoter mutant might contriBute to the gender difference of the progression of liver disease in HBeAg-negative chronic <B>HepatitisB> B in Taiwan.

  • <B>HepatitisB> B virus genotypes and spontaneous <B>HepatitisB> B e antigen seroconversion in taiwanese <B>HepatitisB> B carriers
    Journal of Medical Virology, 2004
    Co-Authors: Jiahorng Kao, Peijer Chen, Ming Yang Lai, Dingshinn Chen
    Abstract:

    <B>HepatitisB> B virus (HBV) is classified into eight genotypes (A–H), and genotype C is associated with more aggressive liver disease compared to genotype B. However, the mechanisms responsiBle for the clinical differences remain unclear. To test whether genotype C patients had with lower rates of spontaneous <B>HepatitisB> B ge antigen (HBeAg) seroconversion than genotype B patients, stored serum samples from 146 Taiwanese adult HBeAg-positive <B>HepatitisB> B carriers followed-up for a mean of 52 months (range, 12–120 months) were tested for HBV genotype By a molecular method. Genotype C patients were significantly older than genotype B patients (mean age, 37 ± 12 vs. 29 ± 10 years, P < 0.001). During the follow-up period, genotype C patients had a significantly lower rate of spontaneous HBeAg seroconversion than genotype B patients (27 vs. 47%, P < 0.025). Spontaneous HBeAg seroconversion occurred one decade later in genotype C patients compared with genotype B patients. Multivariate analyses identified age ≤35 years (odds ratio: 2.08; 95% confidence interval [CI], 1.07–4.0; P < 0.05), high Baseline serum alanine aminotransferase level (odds ratio: 2.34; 95%CI, 1.39–4.09; P < 0.005), and HBV genotype B (odds ratio: 1.94; 95%CI, 1.03–3.63; P < 0.05) as independent factors associated with spontaneous HBeAg seroconversion. In conclusion, genotype C patients, compared to genotype B patients, have a delayed HBeAg seroconversion in the immune clearance phase of chronic HBV infection, which may contriBute to a more progressive liver disease and more refractory to antiviral therapy. J. Med. Virol. 72:363–369, 2004. © 2004 Wiley-Liss, Inc.

  • efficacy of a mass <B>HepatitisB> B immunization program after switching to recomBinant <B>HepatitisB> B vaccine a population Based study in taiwan
    Vaccine, 2001
    Co-Authors: Hsumei Hsu, Shinchwen Lee, Mingching Wang, Szufong Lin, Dingshinn Chen
    Abstract:

    To study the efficacy of immunization against <B>HepatitisB> B after plasma-derived vaccine was replaced By recomBinant vaccine, 2-year-old Taiwanese children were recruited By stratification random sampling and tested for <B>HepatitisB> B markers. They were grouped according to maternal infectivity and children's immunization status. Of 2010 children, 2.5% had <B>HepatitisB> B surface antigen (HBsAg), 94.1% had its antiBody (anti-HBs), 6.8% had core antiBody, and 3.3% were seronegative. Children of highly infectious mothers immunized with <B>HepatitisB> B immunogloBulin and vaccine on schedule had a lower HBsAg-positive rate and a higher anti-HBs-positive rate than those with vaccine only and off-schedule. The efficacy of the Taiwanese mass <B>HepatitisB> B immunization was maintained after switching to recomBinant <B>HepatitisB> B vaccine.