30 results on '"Batrla-Utermann, R."'
Search Results
2. P0358 : Risk predictors of hepatocellular carcinoma among cirrhotic patients chronically infected with hepatitis B
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Chien, J.D., primary, Liu, J., additional, Lee, M.-H., additional, Jen, C.-L., additional, Batrla-Utermann, R., additional, Lu, S.-N., additional, Wang, L.-Y., additional, You, S.-L., additional, Yang, H.-I., additional, and Chen, C.-J., additional
- Published
- 2015
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3. O016 : Hepatitis B surface antigen and DNA levels can identify inactive carriers and predict lower risk for hepatocellular carcinoma and cirrhosis among genotype B and C chronic hepatitis B carriers
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Liu, J., primary, Yang, H.-I., additional, Lee, M.-H., additional, Batrla-Utermann, R., additional, Jen, C.-L., additional, Lu, S.-N., additional, Wang, L.-Y., additional, You, S.-L., additional, and Chen, C.-J., additional
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- 2015
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4. P0611 : Trajectories of hepatitis B surface antigen and associations with hepatocellular carcinoma, liver cirrhosis, and HBsAg seroclearance among chronic hepatitis B carriers with low viral loads
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Liu, J., primary, Yang, H.-I., additional, Lee, M.-H., additional, Batrla-Utermann, R., additional, Jen, C.-L., additional, Lu, S.-N., additional, Wang, L.-Y., additional, You, S.-L., additional, and Chen, C.-J., additional
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- 2015
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5. Predicting Hepatitis B Virus (HBV) Surface Antigen Seroclearance in HBV e Antigen-Negative Patients With Chronic Hepatitis B: External Validation of a Scoring System
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Liu, J., primary, Tseng, T.-C., additional, Yang, H.-I., additional, Lee, M.-H., additional, Batrla-Utermann, R., additional, Jen, C.-L., additional, Lu, S.-N., additional, Wang, L.-Y., additional, You, S.-L., additional, Chen, P.-J., additional, Chen, C.-J., additional, and Kao, J.-H., additional
- Published
- 2014
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6. P675 RISK PREDICTORS FOR LIVER CANCER AND CIRRHOSIS AMONG CHRONIC HEPATITIS B PATIENTS WITH UNDETECTABLE HEPATITIS B VIRAL LOADS
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Liu, J., primary, Yang, H.-I., additional, Lee, M.-H., additional, Batrla-Utermann, R., additional, Jen, C.-L., additional, Lu, S.-N., additional, Wang, L.-Y., additional, You, S.-L., additional, and Chen, C.-J., additional
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- 2014
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7. P674 SERUM LEVELS OF HEPATITIS B SURFACE ANTIGEN PREDICT LONG-TERM TRAJECTORIES OF HEPATITIS B VIRAL LOAD
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Liu, J., primary, Yang, H.-I., additional, Chen, C.-F., additional, Lee, M.-H., additional, Batrla-Utermann, R., additional, Jen, C.-L., additional, Lu, S.-N., additional, Wang, L.-Y., additional, You, S.-L., additional, and Chen, C.-J., additional
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- 2014
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8. P668 SERUM INTERLEUKIN 9 LEVEL AS A PREDICTIVE MARKER OF SPONTANEOUS SEROCLEARANCE OF HEPATITIS B SURFACE ANTIGEN IN CHRONIC HEPATITIS B PATIENTS
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Yang, H.-I., primary, Lee, M.-H., additional, Liu, J., additional, Chien, Y.-C., additional, Chen, H.-Y., additional, Liu, C.-J., additional, Jen, C.-L., additional, Batrla-Utermann, R., additional, and Chen, C.-J., additional
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- 2014
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9. THU-127 - Serum Levels of Wisteria Floribunda Agglutinin-Positive MAC-2 Binding Protein as Short-Term Predictors of Hepatocellular Carcinoma in Chronic Hepatitis B
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Liu, J., Hu, H.-H., Yang, H.-I., Korenaga, M., Lee, M.-H., Jen, C.-L., Batrla-Utermann, R., Lu, S.-N., Wang, L.-Y., You, S.-L., Mizokami, M., and Chen, C.-J.
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- 2016
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10. 687 SERUM IP-10 LEVEL ASSOCIATED WITH HEPATOCELLULAR CARCINOMA DEVELOPMENT IN PATIENTS WITH CHRONIC HEPATITIS B
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Yang, H.-I., primary, Chien, Y.-C., additional, Lee, M.-H., additional, Liu, J., additional, Chen, H.-Y., additional, Liu, C.-J., additional, Jen, C.-L., additional, Tsai, D., additional, Batrla-Utermann, R., additional, Iloeje, U., additional, Chen, P.-J., additional, and Chen, C.-J., additional
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- 2013
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11. 473 DEVELOPMENT OF PREDICTION MODELS FOR HBV-RELATED LIVER CIRRHOSIS BY INTEGARTING HBV GENOTYPE AND SERUM LEVELS OF HBV DNA AND HBSAG
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Lee, M.-H., primary, Yang, H.-I., additional, Liu, J., additional, Batrla-Utermann, R., additional, Jen, C.-L., additional, Iloeje, U.H., additional, Su, J., additional, Lu, S.-N., additional, You, S.-L., additional, Wang, L.-Y., additional, and Chen, C.-J., additional
- Published
- 2012
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12. 475 DIFFERENCES IN THE ROLE OF QUANTITATIVE HEPATITIS B SURFACE ANTIGEN BETWEEN HBEAG SEROPOSITIVE AND SERONEGATIVE INDIVIDUALS WITH CHRONIC HEPATITIS B
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Liu, J., primary, Lee, M.-H., additional, Batrla-Utermann, R., additional, Jen, C.-L., additional, Iloeje, U.H., additional, Lu, S.-N., additional, Wang, L.-Y., additional, You, S.-L., additional, Hsiao, K.C., additional, Yang, H.-I., additional, and Chen, C.-J., additional
- Published
- 2012
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13. 461 INTEGRATING QUANTITIATIVE SERUM HBSAG LEVELS INTO RISK SCORES FOR PREDICTING HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS B PATIENTS
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Chen, C.-J., primary, Lee, M.-H., additional, Yang, H.-I., additional, Liu, J., additional, Batrla-Utermann, R., additional, Jen, C.-L., additional, Iloeje, U.H., additional, Su, J., additional, Lu, S.-N., additional, You, S.-L., additional, and Wang, L.-Y., additional
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- 2012
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14. 567 RELATIONSHIP BETWEEN HBV CCCDNA AND HBsAg LEVELS IS ASSOCIATED WITH HBeAg STATUSES OF CHRONIC HEPATITIS B PATIENTS
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Lu, L., primary, Ye, D.-W., additional, Wang, Y.-D., additional, Kwok, A.Y.K., additional, Wong, A., additional, Yueng, Y.-H., additional, Zhang, H.-Y., additional, Bowden, S., additional, Batrla-Utermann, R., additional, Locarnini, S., additional, and Lau, G.K.K., additional
- Published
- 2009
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15. Persistently high HBsAg levels during HBeAg-seropositive stage predict lower risk of hepatocellular carcinoma in chronic hepatitis B patients.
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Lin HC, Jeng WJ, Liu J, Pan MH, Lee MH, Batrla-Utermann R, Lu SN, Chen CF, Yang HI, and Chen CJ
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- Humans, Adult, Hepatitis B Surface Antigens, Hepatitis B e Antigens, DNA, Viral genetics, Hepatitis B virus genetics, Carcinoma, Hepatocellular etiology, Carcinoma, Hepatocellular genetics, Hepatitis B, Chronic epidemiology, Liver Neoplasms etiology, Liver Neoplasms genetics
- Abstract
Background: High hepatitis B surface antigen (HBsAg) level predicts hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients with low viral load. The role of longitudinal HBsAg levels in predicting HCC in HBeAg-positive CHB patients remains unknown., Method: HBeAg-positive CHB participants from the REVEAL-HBV cohort with ≥2 HBsAg measurements before HBeAg seroclearance were enrolled. Group-based trajectory modelling identified distinct HBsAg trajectory groups during a median of 11 years of HBeAg-positive status. Cox regression models were applied for investigating independent predictors of HCC and estimating adjusted hazard ratio (HR
adj ) with a 95% confidence interval (CI). A p-value less than 0.05 was considered statistically significant., Results: A total of 319 patients were enrolled and classified by HBsAg trajectory patterns as (A) persistently high group (n = 72): HBsAg persistently ≥104 IU/mL, and (B) non-stationary group (n = 233): low HBsAg at baseline or declining to <104 IU/mL during the follow-up. Group B had higher proportions of abnormal ALT levels, HBV genotype C and basal core mutation than group A (p < 0.05); age at entry and gender were comparable. The annual incidence of HCC in group A and group B were 0.37% and 1.16%, respectively (p = 0.03). In multivariate analysis, age >40 years (HRadj [95% CI] = 4.11 [2.26-7.48]), genotype C (HRadj [95% CI] = 4.39 [1.96-9.81]) and the non-stationary group (HRadj [95% CI] = 3.50 [1.49-8.21]) were independent predictors of HCC. Basal core promoter mutation was the only risk factor of HCC in the persistently high HBsAg group (HRadj [95% CI] = 32.75 [5.41-198.42])., Conclusion: Patients with persistently high HBsAg levels during HBeAg-seropositive stage represent a unique population with low risk of HCC development., (© 2024 John Wiley & Sons Ltd.)- Published
- 2024
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16. Rapid Decline Rather Than Absolute Level of HBsAg Predicts Its Seroclearance in Untreated Chronic Hepatitis B Patients From Taiwanese Communities.
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Lin HC, Liu J, Pan MH, Lee MH, Batrla-Utermann R, Lu SN, Jeng WJ, Yang HI, and Chen CJ
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- Humans, Hepatitis B virus genetics, DNA, Predictive Value of Tests, Hepatitis B Surface Antigens, Hepatitis B, Chronic diagnosis, Hepatitis B, Chronic drug therapy
- Abstract
Introduction: Hepatitis B surface antigen (HBsAg) clearance leads to favorable outcomes in patients with chronic hepatitis B. HBsAg levels <200 IU/mL with HBsAg decline >0.5 log 10 IU/mL in 1 year have been reportedly predictive of HBsAg loss. This study aimed to use the REVEAL-hepatitis B virus cohort to validate and simplify this prediction rule and verify whether the simplified algorithm can be used among various clinical subgroups., Method: We analyzed 707 patients with untreated chronic hepatitis B who had 3 or more HBsAg measurements within 5 years before HBsAg seroclearance or last visit, greater than 1 year apart from one another. Rapid HBsAg decline was defined as HBsAg decline >0.5 log 10 IU/mL in 1 year or >1 log 10 IU/mL in 2 years. Sensitivity, specificity, positive predictive values, and negative predictive values were compared to assess the predictability of HBsAg seroclearance., Results: During a median follow-up of 10.7 years, 41 of the 707 patients cleared serum HBsAg. HBsAg levels at all measurements were lower ( P < 0.0001) and HBsAg decline was greater ( P < 0.0001) in patients with seroclearance compared with non-seroclearance patients. The predictive accuracy of predicting 1-year HBsAg loss using only the rapid decline algorithm (sensitivity = 0.4412, specificity = 0.9792, positive predictive value = 0.5172, negative predictive value = 0.972) was the same as the model combining rapid HBsAg decline and HBsAg levels <200 IU/mL. The simplified algorithm including only the rapid decline performed similarly among various levels of HBsAg, hepatitis B virus DNA, and alanine aminotransferase and was independent of inactive carrier state., Discussion: HBsAg decline >0.5 log 10 IU/mL/yr was a practical predictor of HBsAg seroclearance within 1 year in our community-based untreated cohort., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)
- Published
- 2023
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17. CSF biomarkers in Olmsted County: Evidence of 2 subclasses and associations with demographics.
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Van Harten AC, Wiste HJ, Weigand SD, Mielke MM, Kremers WK, Eichenlaub U, Batrla-Utermann R, Dyer RB, Algeciras-Schimnich A, Knopman DS, Jack CR Jr, and Petersen RC
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- Aged, Aged, 80 and over, Aging pathology, Amyloid beta-Peptides cerebrospinal fluid, Biomarkers cerebrospinal fluid, Cognitive Dysfunction epidemiology, Female, Humans, Male, Middle Aged, Minnesota epidemiology, Peptide Fragments cerebrospinal fluid, Positron-Emission Tomography methods, Spinal Puncture methods, tau Proteins cerebrospinal fluid, Aging cerebrospinal fluid, Cognitive Dysfunction cerebrospinal fluid, Cognitive Dysfunction diagnostic imaging, Evidence-Based Medicine methods
- Abstract
Objective: We studied interrelationships between CSF biomarkers and associations with APOE ε4 genotype, demographic variables, vascular variables, and clinical diagnosis in Olmsted County, Minnesota., Methods: We included 774 Mayo Clinic Study of Aging participants (693 cognitively unimpaired [CU]; 71 with mild cognitive impairment [MCI]). CSF β-amyloid 42 (Aβ42), total tau (t-tau), and hyperphosphorylated tau (p-tau) were analyzed using Aβ42 CSF, t-tau CSF, and p-tau (181P) CSF electrochemiluminescence immunoassays. Bivariate mixture models were used to evaluate latent classes. We used linear regression models to evaluate independent associations of APOE ε4, demographic factors, cardiovascular risk, and diagnosis with CSF biomarker levels. Results were weighted back to the Olmsted County population., Results: Interrelationships between CSF Aβ42 and p-tau/t-tau were consistent with 2 latent classes in the general population. In subgroup 1 (n = 547 [71%]), we found a strong positive correlation between Aβ42 and p-tau (ρ = 0.81), while the correlation was much smaller in group 2 (ρ = 0.26, n = 227 [29%]). Group 2 was associated with older age, APOE ε4 genotype, a diagnosis of MCI, and elevated amyloid PET. Overall, APOE ε4 genotype and MCI were associated with Aβ42, while age was associated with p-tau/t-tau. There were no associations with sex, education, or vascular risk., Conclusion: We hypothesize the population without dementia can be subdivided into participants with and without biological Alzheimer disease (AD) based on the combination of CSF Aβ42 and p-tau/t-tau (represented also by the p-tau/t-tau/Aβ42 ratio). In those without biological AD, common factors such as CSF dynamics may cause a positive correlation between CSF Aβ42 and p-tau/t-tau, while AD leads to dissociation of these proteins., (© 2020 American Academy of Neurology.)
- Published
- 2020
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18. Cerebrospinal fluid biomarkers measured by Elecsys assays compared to amyloid imaging.
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Schindler SE, Gray JD, Gordon BA, Xiong C, Batrla-Utermann R, Quan M, Wahl S, Benzinger TLS, Holtzman DM, Morris JC, and Fagan AM
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- Aged, Amyloid beta-Peptides cerebrospinal fluid, Aniline Compounds, Biomarkers cerebrospinal fluid, Cohort Studies, Female, Humans, Male, Middle Aged, Peptide Fragments cerebrospinal fluid, Radiopharmaceuticals, Thiazoles, tau Proteins cerebrospinal fluid, Alzheimer Disease diagnosis, Amyloid metabolism, Brain diagnostic imaging, Brain metabolism, Immunoassay, Positron-Emission Tomography
- Abstract
Introduction: Levels of amyloid β peptide 42 (Aβ42), total tau, and phosphorylated tau-181 are well-established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, but variability in manual plate-based assays has limited their use. We examined the relationship between CSF biomarkers, as measured by a novel automated immunoassay platform, and amyloid positron emission tomography., Methods: CSF samples from 200 individuals underwent separate analysis for Aβ42, total tau, and phosphorylated tau-181 with automated Roche Elecsys assays. Aβ40 was measured with a commercial plate-based assay. Positron emission tomography with Pittsburgh Compound B was performed less than 1 year from CSF collection., Results: Ratios of CSF biomarkers (total tau/Aβ42, phosphorylated tau-181/Aβ42, and Aβ42/Aβ40) best discriminated Pittsburgh Compound B-positive from Pittsburgh Compound B-negative individuals., Discussion: CSF biomarkers and amyloid positron emission tomography reflect different aspects of Alzheimer's disease brain pathology, and therefore, less-than-perfect correspondence is expected. Automated assays are likely to increase the utility of CSF biomarkers., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2018
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19. Serum Levels of M2BPGi as Short-Term Predictors of Hepatocellular Carcinoma in Untreated Chronic Hepatitis B Patients.
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Liu J, Hu HH, Lee MH, Korenaga M, Jen CL, Batrla-Utermann R, Lu SN, Wang LY, Mizokami M, Chen CJ, and Yang HI
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- Adult, Aged, Antigens, Neoplasm blood, Antiviral Agents therapeutic use, Area Under Curve, Biomarkers, Tumor blood, Carcinoma, Hepatocellular blood, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular metabolism, Carrier Proteins blood, Case-Control Studies, Female, Glycoproteins blood, Hepatitis B Surface Antigens analysis, Hepatitis B Surface Antigens blood, Hepatitis B, Chronic complications, Hepatitis B, Chronic drug therapy, Humans, Liver Cirrhosis complications, Liver Neoplasms blood supply, Liver Neoplasms drug therapy, Liver Neoplasms metabolism, Male, Middle Aged, Prognosis, ROC Curve, alpha-Fetoproteins analysis, Antigens, Neoplasm analysis, Biomarkers, Tumor analysis, Carrier Proteins analysis, Glycoproteins analysis
- Abstract
This study examines the role of M2BPGi, a novel seromarker for chronic hepatitis, in predicting hepatocellular carcinoma (HCC) among untreated chronic hepatitis B (CHB) patients. In this nested case-control study, 1070 samples were assayed for M2BPGi, including 357 samples from HCC cases, and 713 samples from non-HCC controls, collected at various times throughout follow-up. HCC case samples were stratified according to years prior to diagnosis. Associations between M2BPGi and HCC were examined with multivariate logistic regression. M2BPGi, α-fetoprotein (AFP), and hepatitis B surface antigen (HBsAg) levels were significant independent short-term predictors of HCC, while M2BPGi was insignificant in long-term analyses. Compared to M2BPGi levels <1.0 cut-off index (COI), those with levels ≥2.0 COI had multivariate odds ratios (95% CI) for HCC of 7.40 (2.40-22.78), 6.46 (2.58-16.18), and 2.24 (0.97-5.15), respectively, for prediction of HCC within 1-2, 2-5, and ≥5 years. Higher proportions of individuals had M2BPGi levels ≥2.0 COI in samples closer to HCC diagnosis. Areas under receiver operating characteristic curves for models with M2BPGi, AFP, and HBsAg levels predicting HCC within 1-2, 2-5, and >5 years were 0.84, 0.81, and 0.75. M2BPGi is a strong and independent short-term predictor of HCC in CHB patients.
- Published
- 2017
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20. Alzheimer's biomarkers in daily practice (ABIDE) project: Rationale and design.
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de Wilde A, van Maurik IS, Kunneman M, Bouwman F, Zwan M, Willemse EA, Biessels GJ, Minkman M, Pel R, Schoonenboom NS, Smets EM, Wattjes MP, Barkhof F, Stephens A, van Lier EJ, Batrla-Utermann R, Scheltens P, Teunissen CE, van Berckel BN, and van der Flier WM
- Abstract
Introduction: The Alzheimer's biomarkers in daily practice (ABIDE) project is designed to translate knowledge on diagnostic tests (magnetic resonance imaging [MRI], cerebrospinal fluid [CSF], and amyloid positron emission tomography [PET]) to daily clinical practice with a focus on mild cognitive impairment (MCI)., Methods: ABIDE is a 3-year project with a multifaceted design and is structured into interconnected substudies using both quantitative and qualitative research methods., Results: Based on retrospective data, we develop personalized risk estimates for MCI patients. Prospectively, we collect MRI and CSF data from 200 patients from local memory clinics and amyloid PET from 500 patients in a tertiary setting, to optimize application of these tests in daily practice. Furthermore, ABIDE will develop strategies for optimal patient-clinician conversations., Discussion: Ultimately, this will result in a set of practical tools for clinicians to support the choice of diagnostic tests and facilitate the interpretation and communication of their results.
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- 2017
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21. Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic.
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O'Bryant SE, Mielke MM, Rissman RA, Lista S, Vanderstichele H, Zetterberg H, Lewczuk P, Posner H, Hall J, Johnson L, Fong YL, Luthman J, Jeromin A, Batrla-Utermann R, Villarreal A, Britton G, Snyder PJ, Henriksen K, Grammas P, Gupta V, Martins R, and Hampel H
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- Female, Humans, Male, Reproducibility of Results, Alzheimer Disease blood, Biomarkers blood, Cooperative Behavior, Public-Private Sector Partnerships
- Abstract
The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer's disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patient acceptance. Despite these advantages and increased research efforts, the field has been hampered by lack of reproducibility and an unclear path for moving basic discovery toward clinical utilization. Here we reviewed the recent literature on blood-based biomarkers in AD to provide a current state of the art. In addition, a collaborative model is proposed that leverages academic and industry strengths to facilitate the field in moving past discovery only work and toward clinical use. Key resources are provided. This new public-private partnership model is intended to circumvent the traditional handoff model and provide a clear and useful paradigm for the advancement of biomarker science in AD and other neurodegenerative diseases., (Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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22. Cerebrospinal Fluid Biomarkers for Alzheimer's Disease: A View of the Regulatory Science Qualification Landscape from the Coalition Against Major Diseases CSF Biomarker Team.
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Arnerić SP, Batrla-Utermann R, Beckett L, Bittner T, Blennow K, Carter L, Dean R, Engelborghs S, Genius J, Gordon MF, Hitchcock J, Kaplow J, Luthman J, Meibach R, Raunig D, Romero K, Samtani MN, Savage M, Shaw L, Stephenson D, Umek RM, Vanderstichele H, Willis B, and Yule S
- Subjects
- Clinical Trials as Topic, Drug Approval, Drug Discovery, Humans, Alzheimer Disease cerebrospinal fluid, Biomarkers cerebrospinal fluid
- Abstract
Alzheimer's disease (AD) drug development is burdened with the current requirement to conduct large, lengthy, and costly trials to overcome uncertainty in patient progression and effect size on treatment outcome measures. There is an urgent need for the discovery, development, and implementation of novel, objectively measured biomarkers for AD that would aid selection of the appropriate subpopulation of patients in clinical trials, and presumably, improve the likelihood of successfully evaluating innovative treatment options. Amyloid deposition and tau in the brain, which are most commonly assessed either in cerebrospinal fluid (CSF) or by molecular imaging, are consistently and widely accepted. Nonetheless, a clear gap still exists in the accurate identification of subjects that truly have the hallmarks of AD. The Coalition Against Major Diseases (CAMD), one of 12 consortia of the Critical Path Institute (C-Path), aims to streamline drug development for AD and related dementias by advancing regulatory approved drug development tools for clinical trials through precompetitive data sharing and adoption of consensus clinical data standards. This report focuses on the regulatory process for biomarker qualification, briefly comments on how it contrasts with approval or clearance of companion diagnostics, details the qualifications currently available to the field of AD, and highlights the current challenges facing the landscape of CSF biomarkers qualified as hallmarks of AD. Finally, it recommends actions to accelerate regulatory qualification of CSF biomarkers that would, in turn, improve the efficiency of AD therapeutic development.
- Published
- 2017
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23. Risk and predictors of hepatocellular carcinoma for chronic hepatitis B patients with newly developed cirrhosis.
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Chien J, Liu J, Lee MH, Jen CL, Batrla-Utermann R, Lu SN, Wang LY, You SL, Yang HI, and Chen CJ
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- Adult, Age Factors, Aged, Aldehyde Dehydrogenase, Mitochondrial genetics, Biomarkers, Tumor blood, Biomarkers, Tumor genetics, Carcinoma, Hepatocellular blood, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular epidemiology, Disease Progression, Female, Genetic Predisposition to Disease, Hepatitis B Surface Antigens blood, Hepatitis B, Chronic blood, Hepatitis B, Chronic diagnosis, Hepatitis B, Chronic epidemiology, Humans, Incidence, Liver Cirrhosis blood, Liver Cirrhosis diagnosis, Liver Cirrhosis epidemiology, Liver Neoplasms blood, Liver Neoplasms diagnosis, Liver Neoplasms epidemiology, Male, Middle Aged, Multivariate Analysis, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Taiwan epidemiology, Time Factors, alpha-Fetoproteins metabolism, Carcinoma, Hepatocellular virology, Hepatitis B, Chronic complications, Liver Cirrhosis virology, Liver Neoplasms virology
- Abstract
Background and Aims: Most studies on risk predictors of hepatocellular carcinoma (HCC) among cirrhotic chronic hepatitis B patients do not confirm the date at cirrhosis diagnosis. We examined HCC risk and predictors in chronic hepatitis B patients with newly diagnosed cirrhosis., Methods: 4155 HBsAg seropositive participants were followed every 6-12 months with seromarker testing. Cirrhosis was ascertained through abdominal ultrasonography and computerized linkage with national health insurance profiles. Predictors included in Cox proportional hazards models were age, HBeAg serostatus, serum levels of HBsAg, alanine aminotransferase (ALT), alpha-fetoprotein (AFP), and ALDH2 rs671 genotypes., Results: A total of 301 patients developed cirrhosis, 76 of whom later developed HCC after 2462 person-years, showing an average annual incidence of 3.1%. The 15-year cumulative HCC risk among cirrhotics was 39.8% with a lifetime (30-80 years old) HCC risk of 78.5%. The adjusted HR's (95% CI, P-value) were 14.26 (3.17-64.08, P = 0.0005) for age at cirrhosis diagnosis of ≥60 years (vs 30-39 years), 2.85 (1.49-5.46, P = 0.0015) for HBeAg seropositivity (vs HBeAg seronegativity with HBsAg levels <1000 IU/mL), 0.35 (0.20-0.59, P < 0.0001) for AA/AG genotypes of rs671 (vs GG genotype), 3.68 (1.70-7.99, P = 0.0010) for ALT levels >45 U/L (vs <15 U/L), 3.52 (1.78-6.93, P = 0.0003) for AFP levels >20 ng/mL (vs <10 ng/mL), and 2.64 (1.38-5.07, P = 0.0035) for HBsAg levels ≥1000 IU/mL (vs <1000 IU/mL among HBeAg seronegatives)., Conclusions: Older age, GG genotype of ALDH2 rs671, HBeAg seropositivity, and elevated serum levels of ALT, AFP, and HBsAg at cirrhosis diagnosis were HCC risk predictors in cirrhotic chronic hepatitis B patients., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
- Published
- 2016
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24. Serum Levels of Hepatitis B Surface Antigen and DNA Can Predict Inactive Carriers With Low Risk of Disease Progression.
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Liu J, Yang HI, Lee MH, Jen CL, Batrla-Utermann R, Lu SN, Wang LY, You SL, and Chen CJ
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- Adult, Aged, Carcinoma, Hepatocellular blood, Carcinoma, Hepatocellular virology, Cohort Studies, Disease Progression, Female, Hepatitis B virus genetics, Hepatitis B, Chronic complications, Humans, Liver Cirrhosis blood, Liver Cirrhosis virology, Liver Neoplasms blood, Liver Neoplasms virology, Male, Middle Aged, DNA, Viral blood, Hepatitis B Surface Antigens blood, Hepatitis B virus isolation & purification, Hepatitis B, Chronic blood
- Abstract
Unlabelled: Serum levels of hepatitis B virus (HBV) DNA (≤2000 IU/mL) and hepatitis B surface antigen (HBsAg) (<1000 IU/mL) have been shown to distinguish inactive carriers with high accuracy. The goal of this study was to validate the predictability of one-time measurement of quantitative HBsAg and HBV DNA levels for inactive carrier status and chronic hepatitis B (CHB) progression in a community-based cohort. This study included 1529 participants chronically infected with HBV genotype B or C from the REVEAL-HBV cohort. They were ascertained as inactive or active CHB after 18 months of follow-up. Validity of the one-time measurement was assessed by sensitivity, specificity, and receiver operating characteristic curves, while associations with clinical outcomes were calculated with Cox proportional hazards regressions. The one-time baseline measurement of HBsAg <1000 IU/mL and HBV DNA <2000 IU/mL distinguished inactive carriers from active CHB with a sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 71%, 85%, 83%, 74%, and 78%, respectively. Those identified as inactive carriers using the one-time baseline measurement had multivariate adjusted hazard ratios of 0.36 (95% confidence interval [CI], 0.20-0.63) and 0.36 (0.23-0.56) for hepatocellular carcinoma and liver cirrhosis, respectively, and an adjusted rate ratio of 6.97 (95% CI, 5.21-9.33) for HBsAg seroclearance. Areas under the receiver operating characteristic curve of predicting these outcomes using the one-time definition were similar to those obtained when using long-term follow-up defined carrier status for prediction., Conclusion: This study confirms the predictability of a one-time combined HBsAg and HBV DNA measurement for future inactive carriers. This single-point strategy provides new and complementary information useful for management of patients with chronic hepatitis B infection. (Hepatology 2016;64:381-389)., (© 2016 by the American Association for the Study of Liver Diseases.)
- Published
- 2016
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25. Incorporating Serum Level of Hepatitis B Surface Antigen or Omitting Level of Hepatitis B Virus DNA Does not Affect Calculation of Risk for Hepatocellular Carcinoma in Patients Without Cirrhosis.
- Author
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Yang HI, Tseng TC, Liu J, Lee MH, Liu CJ, Su TH, Batrla-Utermann R, Chan HL, Kao JH, and Chen CJ
- Subjects
- Adult, Aged, Female, Hong Kong, Hospitals, University, Humans, Liver Cirrhosis complications, Liver Cirrhosis pathology, Male, Middle Aged, Prognosis, Prospective Studies, Risk Assessment, Taiwan, Carcinoma, Hepatocellular diagnosis, DNA, Viral blood, Hepatitis B Surface Antigens blood, Hepatitis B, Chronic complications, Hepatitis B, Chronic pathology, Serum chemistry
- Abstract
Background & Aims: Tests for hepatitis B virus (HBV) DNA are expensive, and levels of hepatitis B surface antigen (HBsAg) can help determine the risk for hepatocellular carcinoma (HCC) in patients with chronic HBV infection. We investigated how adding data to knowing the level of HBsAg or excluding measurement of HBV DNA affected the accuracy of the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) scoring system in determining the risk for HCC., Methods: We collected data from 3584 patients with chronic HBV infection who were positive for HBsAg, free of cirrhosis, and participated in the community-based Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer (REVEAL)-HBV cohort (208 cases of HCC) from 1991 through 1992; they were followed up until December 31, 2008. Data from this cohort were used to derive our scoring system. We validated our system using data from 2688 HBsAg-seropositive patients (191 cases of HCC) who participated in the hospital-based Elucidation of Risk Factors for Disease Control or Advancement in Taiwanese Hepatitis B Carriers (ERADICATE-B) study at the National Taiwan University Hospital from 1985 through 2000; they were followed up until December 31, 2010. We also validated the system using data from 426 patients with chronic HBV infection who participated in the Chinese University of Hong Kong (CUHK) study (46 cases of HCC) from 1997 through 2000; patients were followed up for a median of 225 weeks. Discrimination and calibration were evaluated using area under the receiver operating characteristic (AUROC) curves and calibration charts., Results: When data on HBsAg were added to the REACH-B scoring system, it identified patients in the ERADICATE-B study who developed HCC within 3, 5, and 10 years, with AUROC curve values of 0.92 (95% confidence interval [CI], 0.82-1.02), 0.78 (95% CI, 0.70-0.86), and 0.80 (95% CI, 0.76-0.84), respectively. It identified patients in the CUHK study who developed HCC in 3, 5, and 10 years, with AUROC curve values of 0.85 (95% CI, 0.75-0.95), 0.82 (95% CI, 0.70-0.93), and 0.78 (95% CI, 0.70-0.870), respectively. When data on HBV DNA were removed from the REACH-B scoring system, it identified patients in the ERADICATE-B cohort who developed HCC in 3, 5, and 10 years, with AUROC curve values of 0.90 (95% CI, 0.81-1.0), 0.76 (95% CI, 0.68-0.85), and 0.78 (95% CI, 0.73-0.82), respectively. It identified patents in the CUHK cohort who developed HCC in 3, 5, and 10 years, with AUROC curve values of 0.84 (95% CI, 0.79-0.92), 0.81 (95% CI, 0.71-0.91), and 0.79 (95% CI, 0.72-0.87). These modified systems identified patients who developed HCC with similar levels of accuracy as the original REACH-B score (P > .05 in tests of noninferiority)., Conclusions: Including data on serum level of HBsAg or removing data on level of HBV DNA do not alter the accuracy of the REACH-B scoring system in determining HCC risk in patients with chronic HBV infection without cirrhosis. It might be cost effective to replace the test for HBV DNA with assays to measure HBsAg in determining HCC risk. These modified scoring systems might replace the REACH-B system in specific situations., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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26. Predicting Hepatitis B Virus (HBV) Surface Antigen Seroclearance in HBV e Antigen-Negative Patients With Chronic Hepatitis B: External Validation of a Scoring System.
- Author
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Liu J, Tseng TC, Yang HI, Lee MH, Batrla-Utermann R, Jen CL, Lu SN, Wang LY, You SL, Chen PJ, Chen CJ, and Kao JH
- Subjects
- Adult, Aged, Cohort Studies, DNA, Viral blood, DNA, Viral genetics, Female, Genotype, Hepatitis B virus classification, Hepatitis B virus genetics, Humans, Male, Middle Aged, Prognosis, Taiwan, Hepatitis B Surface Antigens blood, Hepatitis B e Antigens blood, Hepatitis B, Chronic diagnosis, Hepatitis B, Chronic virology, Severity of Illness Index
- Abstract
Background: Hepatitis B virus (HBV) surface antigen (HBsAg) seroclearance is the ultimate serological end point in chronic hepatitis B. This study aimed to develop and validate a prediction score for spontaneous HBsAg seroclearance in HBV e antigen (HBeAg)-negative patients with chronic hepatitis B due to HBV genotype B or C., Methods: The development cohort included 2491 untreated participants from the community-based REVEAL-HBV study, who were HBeAg negative, anti-hepatitis C virus negative, and cirrhosis free. The independent validation cohort consisted of 1934 hospital-based individuals from the National Taiwan University Hospital. Clinical markers included in the model were age and serum HBV DNA and HBsAg levels. Cox proportional hazards regression models were used to create the prediction model., Results: A prediction score ranging from 0 to 27 was developed. Predicted probabilities of 5- and 10-year HBsAg seroclearance ranged from 0.95% to 30.49% and from 2.58% to 62.52%, respectively. When applied to the independent validation cohort, the areas under the receiver operating characteristic curves for the 5- and 10-year prediction of HBsAg seroclearance in the validation cohort were 0.82 (95% confidence interval [CI], .76-.88) and 0.74 (95% CI, .70-.78). Model fit was still adequate, according to Hosmer-Lemeshow goodness of fit tests., Conclusions: A clinically applicable prediction score for HBsAg seroclearance was developed and externally validated. This model can assist clinicians in further stratifying risk groups., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2015
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27. Spontaneous seroclearance of hepatitis B seromarkers and subsequent risk of hepatocellular carcinoma.
- Author
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Liu J, Yang HI, Lee MH, Lu SN, Jen CL, Batrla-Utermann R, Wang LY, You SL, Hsiao CK, Chen PJ, and Chen CJ
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Proportional Hazards Models, Risk Factors, Taiwan, Biomarkers blood, Carcinoma, Hepatocellular physiopathology, DNA, Viral blood, Hepatitis B blood, Hepatitis B Surface Antigens blood, Hepatitis B e Antigens blood, Liver Neoplasms physiopathology
- Abstract
Background and Aims: The associations between long-term risk of hepatocellular carcinoma (HCC) and spontaneous seroclearance of HBV e antigen (HBeAg), HBV DNA and HBV surface antigen (HBsAg) have never been examined by a prospective study using serially measured seromarkers. This study aimed to assess the importance of spontaneous HBeAg, HBV DNA and HBsAg seroclearance in the prediction of HCC risk., Methods: This study included 2946 HBsAg seropositive individuals who were seronegative for antibodies against HCV and free of liver cirrhosis. Serial serum samples collected at study entry and follow-up health examinations were tested for HBeAg, HBV DNA and HBsAg. Cox proportional hazards models were used to calculate the HRs of developing HCC after seroclearance of HBV markers., Results: The HR (95% CI) of developing HCC after seroclearance of HBeAg, HBV DNA and HBsAg during follow-up was 0.63 (0.38 to 1.05), 0.24 (0.11 to 0.57) and 0.18 (0.09 to 0.38), respectively, after adjustment for age, gender and serum level of alanine aminotransferase at study entry. High HBV DNA levels at the seroclearance of HBeAg (mean±SD, 4.35±1.64 log10 IU/mL) may explain the non-significant association between HBeAg seroclearance and HCC risk. Among HBeAg seronegative participants with detectable serum HBV DNA at study entry, the lifetime (30-75-years-old) cumulative incidence of HCC was 4.0%, 6.6% and 14.2%, respectively, for those with seroclearance of both HBV DNA and HBsAg, seroclearance of HBV DNA only, and seroclearance of neither., Conclusions: Spontaneous seroclearance of HBV DNA and HBsAg are important predictors of reduced HCC risk., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
- Published
- 2014
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28. Distinct seromarkers predict different milestones of chronic hepatitis B progression.
- Author
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Liu J, Yang HI, Lee MH, Batrla-Utermann R, Jen CL, Lu SN, Wang LY, You SL, Hsiao CK, and Chen CJ
- Subjects
- Adult, Aged, Biomarkers blood, Disease Progression, Female, Follow-Up Studies, Genotype, Humans, Incidence, Male, Middle Aged, Predictive Value of Tests, ROC Curve, Risk Factors, Hepacivirus genetics, Hepatitis B Surface Antigens blood, Hepatitis B e Antigens blood, Hepatitis B, Chronic blood, Hepatitis B, Chronic diagnosis, Hepatitis B, Chronic epidemiology
- Abstract
Unlabelled: 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., (© 2014 by the American Association for the Study of Liver Diseases.)
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- 2014
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29. Prediction models of long-term cirrhosis and hepatocellular carcinoma risk in chronic hepatitis B patients: risk scores integrating host and virus profiles.
- Author
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Lee MH, Yang HI, Liu J, Batrla-Utermann R, Jen CL, Iloeje UH, Lu SN, You SL, Wang LY, and Chen CJ
- Subjects
- Adult, Aged, Alanine Transaminase blood, Cohort Studies, DNA, Viral blood, Female, Genotype, Hepatitis B Surface Antigens blood, Hepatitis B, Chronic blood, Humans, Male, Middle Aged, Risk Assessment, Risk Factors, Time Factors, Viral Load, Carcinoma, Hepatocellular epidemiology, Hepatitis B virus genetics, Hepatitis B virus immunology, Hepatitis B, Chronic complications, Liver Cirrhosis epidemiology, Liver Neoplasms epidemiology, Models, Statistical
- Abstract
Unlabelled: Integrating host and HBV characteristics, this study aimed to develop models for predicting long-term cirrhosis and hepatocellular carcinoma (HCC) risk in chronic hepatitis B virus (HBV) patients. This analysis included hepatitis B surface antigen (HBsAg)-seropositive and anti-HCV-seronegative participants from the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer in HBV (R.E.V.E.A.L.-HBV) cohort. Newly developed cirrhosis and HCC were ascertained through regular follow-up ultrasonography, computerized linkage with national health databases, and medical chart reviews. Two-thirds of the participants were allocated for risk model derivation and another one-third for model validation. The risk prediction model included age, gender, HBV e antigen (HBeAg) serostatus, serum levels of HBV DNA, and alanine aminotransferase (ALT), quantitative serum HBsAg levels, and HBV genotypes. Additionally, the family history was included in the prediction model for HCC. Cox's proportional hazards regression coefficients for cirrhosis and HCC predictors were converted into risk scores. The areas under receiver operating curve (AUROCs) were used to evaluate the performance of risk models. Elder age, male, HBeAg, genotype C, and increasing levels of ALT, HBV DNA, and HBsAg were all significantly associated with an increased risk of cirrhosis and HCC. The risk scores estimated from the derivation set could accurately categorize participants with low, medium, and high cirrhosis and HCC risk in the validation set (P<0.001). The AUROCs for predicting 3-year, 5-year, and 10-year cirrhosis risk ranged 0.83-0.86 and 0.79-0.82 for the derivation and validation sets, respectively. The AUROC for predicting 5-year, 10-year, 15-year risk of HCC ranged 0.86-0.89 and 0.84-0.87 in the derivation and validation sets, respectively., Conclusion: The risk prediction models of cirrhosis and HCC by integrating host and HBV profiles have excellent prediction accuracy and discriminatory ability. They may be used for clinical management of chronic hepatitis B patients., (Copyright © 2013 by the American Association for the Study of Liver Diseases.)
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- 2013
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30. A predictive scoring system for the seroclearance of HBsAg in HBeAg-seronegative chronic hepatitis B patients with genotype B or C infection.
- Author
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Liu J, Lee MH, Batrla-Utermann R, Jen CL, Iloeje UH, Lu SN, Wang LY, You SL, Hsiao CK, Yang HI, and Chen CJ
- Subjects
- Adult, Aged, Antiviral Agents therapeutic use, Biomarkers blood, DNA, Viral blood, Female, Humans, Male, Middle Aged, Multivariate Analysis, Predictive Value of Tests, Regression Analysis, Treatment Outcome, Viral Load, Genotype, Hepatitis B Surface Antigens blood, Hepatitis B e Antigens blood, Hepatitis B virus genetics, Hepatitis B, Chronic drug therapy, Hepatitis B, Chronic immunology, Serology methods
- Abstract
Background & Aims: Seroclearance of hepatitis B surface antigen (HBsAg) is the most ideal end point in the treatment of chronic hepatitis B. This study develops a predictive scoring system to assess whether the addition of serum levels HBsAg may improve the predictability of HBsAg loss., Methods: This study included 2491 untreated participants with genotype B or C HBV infection, who were HBsAg-seropositive, HBeAg-seronegative, anti-HCV-seronegative, and cirrhosis free at study entry. Regression coefficients of predictors in Cox Regression models were converted into integer scores for predicting HBsAg seroclearance. Predictive accuracy was assessed with area under the receiver operating characteristic curves (AUROC), and predictive accuracies of models with and without serum HBsAg levels were compared., Results: Low serum levels of both HBsAg and HBV DNA were the strongest predictors of spontaneous HBsAg seroclearance. Compared to baseline serum HBsAg levels ≥1000 IU/ml, the multivariate adjusted rate ratio of spontaneous HBsAg seroclearance was 10.96 (7.92-15.16) for those with baseline serum HBsAg levels <100 IU/ml. The predictive ability of HBsAg levels was modified by HBV viral load, showing a weaker effect in those with higher viral loads, and the strongest effect among those with undetectable viral loads. The inclusion of serum HBsAg levels greatly improved the AUROC for predicting HBsAg seroclearance at the fifth (from 0.79 [0.787-0.792] to 0.89 [0.889-0.891]) and tenth year (from 0.73 [0.728-0.732] to 0.84 [0.839-0.841]) after study entry., Conclusions: Incorporated into an easy-to-use scoring system, HBV viral load and quantitative serum HBsAg levels can accurately predict HBsAg seroclearance., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
- Published
- 2013
- Full Text
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