Distinct seromarkers predict different milestones of chronic hepatitis B progression
Spontaneous seroclearance of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA undetectability are important milestones of chronic hepatitis B and major treatment endpoints of antiviral therapy. This study investigated the role of serum hepatitis B surface antigen (HBsAg) levels and esta...
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| Published in | Hepatology (Baltimore, Md.) Vol. 60; no. 1; pp. 77 - 86 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Wolters Kluwer Health, Inc
01.07.2014
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0270-9139 1527-3350 1527-3350 |
| DOI | 10.1002/hep.27083 |
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| Abstract | Spontaneous seroclearance of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA undetectability are important milestones of chronic hepatitis B and major treatment endpoints of antiviral therapy. This study investigated the role of serum hepatitis B surface antigen (HBsAg) levels and established models for predicting HBeAg seroclearance and HBV DNA undetectability. A total of 2,139 HBsAg‐seropositive, anti‐HCV‐seronegative, and treatment‐naïve participants without liver cirrhosis at study entry were included. Spontaneous HBeAg seroclearance and HBV DNA undetectability were analyzed in 431 HBeAg‐seropositive participants and 1,708 HBeAg‐seronegative participants, respectively. Regression coefficients of predictors in Cox proportional hazard models were converted into integer scores for predicting seroclearance and predictive accuracy was assessed with time‐dependent receiver operating characteristic (ROC) curves. The HBV DNA level was the most important predictor of HBeAg seroclearance but serum HBsAg level was the most significant predictor of HBV DNA undetectability. Compared to individuals with HBsAg levels ≥10,000 IU/mL, the multivariate‐adjusted rate ratio (95% confidence interval) of HBV DNA undetectability was 1.20 (0.62‐2.30), 2.49 (1.31‐4.75), and 6.08 (3.19‐11.61) for those with serum HBsAg levels of 1,000‐9,999, 100‐999, and <100 IU/mL, respectively. The area under the ROC curve (AUROC) of the prediction models for predicting the 5‐ and 10‐year probabilities of HBeAg seroclearance and HBV DNA undetectability were 0.85 (0.80‐0.90) and 0.78 (0.73‐0.83) for HBeAg seroclearance, and 0.77 (0.72‐0.82) and 0.73 (0.70‐0.76) for HBV DNA undetectability. Conclusion: Prediction models incorporating important host and virus factors can predict HBeAg seroclearance and HBV DNA undetectability. Serum HBsAg levels rather than HBV DNA is the most important predictor of spontaneous HBV DNA undetectability. Serum HBsAg levels should be monitored in the management of patients with HBeAg‐seronegative chronic hepatitis B. (Hepatology 2014;60:77–86) |
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| AbstractList | Spontaneous seroclearance of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA undetectability are important milestones of chronic hepatitis B and major treatment endpoints of antiviral therapy. This study investigated the role of serum hepatitis B surface antigen (HBsAg) levels and established models for predicting HBeAg seroclearance and HBV DNA undetectability. A total of 2,139 HBsAg-seropositive, anti-HCV-seronegative, and treatment-naïve participants without liver cirrhosis at study entry were included. Spontaneous HBeAg seroclearance and HBV DNA undetectability were analyzed in 431 HBeAg-seropositive participants and 1,708 HBeAg-seronegative participants, respectively. Regression coefficients of predictors in Cox proportional hazard models were converted into integer scores for predicting seroclearance and predictive accuracy was assessed with time-dependent receiver operating characteristic (ROC) curves. The HBV DNA level was the most important predictor of HBeAg seroclearance but serum HBsAg level was the most significant predictor of HBV DNA undetectability. Compared to individuals with HBsAg levels ≥ 10,000 IU/mL, the multivariate-adjusted rate ratio (95% confidence interval) of HBV DNA undetectability was 1.20 (0.62-2.30), 2.49 (1.31-4.75), and 6.08 (3.19-11.61) for those with serum HBsAg levels of 1,000-9,999, 100-999, and <100 IU/mL, respectively. The area under the ROC curve (AUROC) of the prediction models for predicting the 5- and 10-year probabilities of HBeAg seroclearance and HBV DNA undetectability were 0.85 (0.80-0.90) and 0.78 (0.73-0.83) for HBeAg seroclearance, and 0.77 (0.72-0.82) and 0.73 (0.70-0.76) for HBV DNA undetectability.
Prediction models incorporating important host and virus factors can predict HBeAg seroclearance and HBV DNA undetectability. Serum HBsAg levels rather than HBV DNA is the most important predictor of spontaneous HBV DNA undetectability. Serum HBsAg levels should be monitored in the management of patients with HBeAg-seronegative chronic hepatitis B. Spontaneous seroclearance of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA undetectability are important milestones of chronic hepatitis B and major treatment endpoints of antiviral therapy. This study investigated the role of serum hepatitis B surface antigen (HBsAg) levels and established models for predicting HBeAg seroclearance and HBV DNA undetectability. A total of 2,139 HBsAg-seropositive, anti-HCV-seronegative, and treatment-naïve participants without liver cirrhosis at study entry were included. Spontaneous HBeAg seroclearance and HBV DNA undetectability were analyzed in 431 HBeAg-seropositive participants and 1,708 HBeAg-seronegative participants, respectively. Regression coefficients of predictors in Cox proportional hazard models were converted into integer scores for predicting seroclearance and predictive accuracy was assessed with time-dependent receiver operating characteristic (ROC) curves. The HBV DNA level was the most important predictor of HBeAg seroclearance but serum HBsAg level was the most significant predictor of HBV DNA undetectability. Compared to individuals with HBsAg levels ≥10,000 IU/mL, the multivariate-adjusted rate ratio (95% confidence interval) of HBV DNA undetectability was 1.20 (0.62-2.30), 2.49 (1.31-4.75), and 6.08 (3.19-11.61) for those with serum HBsAg levels of 1,000-9,999, 100-999, and <100 IU/mL, respectively. The area under the ROC curve (AUROC) of the prediction models for predicting the 5- and 10-year probabilities of HBeAg seroclearance and HBV DNA undetectability were 0.85 (0.80-0.90) and 0.78 (0.73-0.83) for HBeAg seroclearance, and 0.77 (0.72-0.82) and 0.73 (0.70-0.76) for HBV DNA undetectability. Conclusion: Prediction models incorporating important host and virus factors can predict HBeAg seroclearance and HBV DNA undetectability. Serum HBsAg levels rather than HBV DNA is the most important predictor of spontaneous HBV DNA undetectability. Serum HBsAg levels should be monitored in the management of patients with HBeAg-seronegative chronic hepatitis B. (Hepatology 2014;60:77-86) [PUBLICATION ABSTRACT] Spontaneous seroclearance of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA undetectability are important milestones of chronic hepatitis B and major treatment endpoints of antiviral therapy. This study investigated the role of serum hepatitis B surface antigen (HBsAg) levels and established models for predicting HBeAg seroclearance and HBV DNA undetectability. A total of 2,139 HBsAg-seropositive, anti-HCV-seronegative, and treatment-naïve participants without liver cirrhosis at study entry were included. Spontaneous HBeAg seroclearance and HBV DNA undetectability were analyzed in 431 HBeAg-seropositive participants and 1,708 HBeAg-seronegative participants, respectively. Regression coefficients of predictors in Cox proportional hazard models were converted into integer scores for predicting seroclearance and predictive accuracy was assessed with time-dependent receiver operating characteristic (ROC) curves. The HBV DNA level was the most important predictor of HBeAg seroclearance but serum HBsAg level was the most significant predictor of HBV DNA undetectability. Compared to individuals with HBsAg levels ≥ 10,000 IU/mL, the multivariate-adjusted rate ratio (95% confidence interval) of HBV DNA undetectability was 1.20 (0.62-2.30), 2.49 (1.31-4.75), and 6.08 (3.19-11.61) for those with serum HBsAg levels of 1,000-9,999, 100-999, and <100 IU/mL, respectively. The area under the ROC curve (AUROC) of the prediction models for predicting the 5- and 10-year probabilities of HBeAg seroclearance and HBV DNA undetectability were 0.85 (0.80-0.90) and 0.78 (0.73-0.83) for HBeAg seroclearance, and 0.77 (0.72-0.82) and 0.73 (0.70-0.76) for HBV DNA undetectability.UNLABELLEDSpontaneous seroclearance of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA undetectability are important milestones of chronic hepatitis B and major treatment endpoints of antiviral therapy. This study investigated the role of serum hepatitis B surface antigen (HBsAg) levels and established models for predicting HBeAg seroclearance and HBV DNA undetectability. A total of 2,139 HBsAg-seropositive, anti-HCV-seronegative, and treatment-naïve participants without liver cirrhosis at study entry were included. Spontaneous HBeAg seroclearance and HBV DNA undetectability were analyzed in 431 HBeAg-seropositive participants and 1,708 HBeAg-seronegative participants, respectively. Regression coefficients of predictors in Cox proportional hazard models were converted into integer scores for predicting seroclearance and predictive accuracy was assessed with time-dependent receiver operating characteristic (ROC) curves. The HBV DNA level was the most important predictor of HBeAg seroclearance but serum HBsAg level was the most significant predictor of HBV DNA undetectability. Compared to individuals with HBsAg levels ≥ 10,000 IU/mL, the multivariate-adjusted rate ratio (95% confidence interval) of HBV DNA undetectability was 1.20 (0.62-2.30), 2.49 (1.31-4.75), and 6.08 (3.19-11.61) for those with serum HBsAg levels of 1,000-9,999, 100-999, and <100 IU/mL, respectively. The area under the ROC curve (AUROC) of the prediction models for predicting the 5- and 10-year probabilities of HBeAg seroclearance and HBV DNA undetectability were 0.85 (0.80-0.90) and 0.78 (0.73-0.83) for HBeAg seroclearance, and 0.77 (0.72-0.82) and 0.73 (0.70-0.76) for HBV DNA undetectability.Prediction models incorporating important host and virus factors can predict HBeAg seroclearance and HBV DNA undetectability. Serum HBsAg levels rather than HBV DNA is the most important predictor of spontaneous HBV DNA undetectability. Serum HBsAg levels should be monitored in the management of patients with HBeAg-seronegative chronic hepatitis B.CONCLUSIONPrediction models incorporating important host and virus factors can predict HBeAg seroclearance and HBV DNA undetectability. Serum HBsAg levels rather than HBV DNA is the most important predictor of spontaneous HBV DNA undetectability. Serum HBsAg levels should be monitored in the management of patients with HBeAg-seronegative chronic hepatitis B. Spontaneous seroclearance of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA undetectability are important milestones of chronic hepatitis B and major treatment endpoints of antiviral therapy. This study investigated the role of serum hepatitis B surface antigen (HBsAg) levels and established models for predicting HBeAg seroclearance and HBV DNA undetectability. A total of 2,139 HBsAg‐seropositive, anti‐HCV‐seronegative, and treatment‐naïve participants without liver cirrhosis at study entry were included. Spontaneous HBeAg seroclearance and HBV DNA undetectability were analyzed in 431 HBeAg‐seropositive participants and 1,708 HBeAg‐seronegative participants, respectively. Regression coefficients of predictors in Cox proportional hazard models were converted into integer scores for predicting seroclearance and predictive accuracy was assessed with time‐dependent receiver operating characteristic (ROC) curves. The HBV DNA level was the most important predictor of HBeAg seroclearance but serum HBsAg level was the most significant predictor of HBV DNA undetectability. Compared to individuals with HBsAg levels ≥10,000 IU/mL, the multivariate‐adjusted rate ratio (95% confidence interval) of HBV DNA undetectability was 1.20 (0.62‐2.30), 2.49 (1.31‐4.75), and 6.08 (3.19‐11.61) for those with serum HBsAg levels of 1,000‐9,999, 100‐999, and <100 IU/mL, respectively. The area under the ROC curve (AUROC) of the prediction models for predicting the 5‐ and 10‐year probabilities of HBeAg seroclearance and HBV DNA undetectability were 0.85 (0.80‐0.90) and 0.78 (0.73‐0.83) for HBeAg seroclearance, and 0.77 (0.72‐0.82) and 0.73 (0.70‐0.76) for HBV DNA undetectability. Conclusion: Prediction models incorporating important host and virus factors can predict HBeAg seroclearance and HBV DNA undetectability. Serum HBsAg levels rather than HBV DNA is the most important predictor of spontaneous HBV DNA undetectability. Serum HBsAg levels should be monitored in the management of patients with HBeAg‐seronegative chronic hepatitis B. (Hepatology 2014;60:77–86) |
| Author | Lu, Sheng‐Nan Hsiao, Chuhsing Kate Yang, Hwai‐I Liu, Jessica Jen, Chin‐Lan Wang, Li‐Yu Chen, Chien‐Jen Lee, Mei‐Hsuan Batrla‐Utermann, Richard You, San‐Lin |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24700432$$D View this record in MEDLINE/PubMed |
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| Copyright | 2014 by the American Association for the Study of Liver Diseases 2014 by the American Association for the Study of Liver Diseases. |
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| Notes | Potential conflict of interest: Dr. Batrla‐Utermann is an employee of and holds stock in Roche Diagnostics. The other authors report no potential conflict of interest. The sponsors of this study had no role in study design, data collection, data analysis, data interpretation, or writing of this report. Moreover, the corresponding author of this article had full access to all data in the study and had final responsibility for the decision to submit the results of this study for publication. Supported by the Department of Health, Taiwan; Bristol‐Myers Squibb Co., USA; Roche Diagnostics, Switzerland; Academia Sinica, Taiwan; and the National Health Research Institutes (NHRI‐EX98‐9806PI), Taiwan. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
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