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Chapter 2.1 40 15. Kao JH. Role of viral factors in the natural course and therapy of chronic hepatitis B. Hepatol Int 2007;1:415-30. 16. Janssen HL, van Zonneveld M, Senturk H, Zeuzem S, Akarca US, Cakaloglu Y, Simon C, So TM, Gerken G, de Man RA, Niesters HG, Zondervan P, Hansen B, Schalm SW. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet 2005;365:123-9. 17. Pas SD, Fries E, De Man RA, Osterhaus AD, Niesters HG. Development of a quantitative real-time detection assay for hepatitis B virus DNA and comparison with two commercial assays. J Clin Microbiol 2000;38:2897-901. 18. Buster EH, Flink HJ, Cakaloglu Y, Simon K, Trojan J, Tabak F, So TM, Feinman SV, Mach T, Akarca US, Schutten M, Tielemans W, van Vuuren AJ, Hansen BE, Janssen HL. Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b. Gastroenterology 2008;135:459-67. 19. Westland C, Delaney Wt, Yang H, Chen SS, Marcellin P, Hadziyannis S, Gish R, Fry J, Brosgart C, Gibbs C, Miller M, Xiong S. Hepatitis B virus genotypes and virologic response in 694 patients in phase III studies of adefovir dipivoxil1. Gastroenterology 2003;125:107-16. 20. Cooksley WG, Piratvisuth T, Lee SD, Mahachai V, Chao YC, Tanwandee T, Chutaputti A, Chang WY, Zahm FE, Pluck N. Peginterferon alpha-2a (40 kDa): an advance in the treatment of hepatitis B e antigen-positive chronic hepatitis B. J Viral Hepat 2003;10:298-305. 21. Fung SK, Lok AS. Hepatitis B virus genotypes: do they play a role in the outcome of HBV infection? Hepatology 2004;40:790-2. 22. Niederau C, Heintges T, Lange S, Goldmann G, Niederau CM, Mohr L, Haussinger D. Longterm follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N Engl J Med 1996;334:1422-7. 23. van Zonneveld M, Honkoop P, Hansen BE, Niesters HG, Murad SD, de Man RA, Schalm SW, Janssen HL. Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B. Hepatology 2004;39:804-10. 24. Flink HJ, Sprengers D, Hansen BE, van Zonneveld M, de Man RA, Schalm SW, Janssen HL. Flares in chronic hepatitis B patients induced by the host or the virus? Relation to treatment response during Peg-interferon {alpha}-2b therapy. Gut 2005;54:1604-9. Acknowledgements We would like to thank Dr. Florian Abel and Dr. Sonja Buyle (Gilead Sciences) for providing us with the placebo data.
Page 1: Statistical Models of Treatment Eff
Page 4 and 5: ISBN: 978-90-8559-069-9 © Bettina
Page 6 and 7: PROMOTIECOMMISSIE Promotor: Prof.dr
Page 9 and 10: CONTENTS Chapter 1. Introduction 11
Page 13: Cha pter 1 Introduction
Page 16 and 17: Chapter 1 14 Epidemiology Worldwide
Page 18 and 19: Chapter 1 16 Prediction models with
Page 20 and 21: Chapter 1 18 standard method fails
Page 22 and 23: Chapter 1 20 The extended non-linea
Page 24 and 25: Chapter 1 22 References 1. Blumberg
Page 27: Cha pter 2 Prediction of response t
Page 30 and 31: Chapter 2.1 28 ABSTRACT The aim of
Page 32 and 33: Chapter 2.1 30 been hepatitis B sur
Page 34 and 35: Chapter 2.1 32 HBV DNA decline The
Page 36 and 37: Chapter 2.1 34 Figure 2 continued.
Page 38 and 39: Chapter 2.1 36 Figure 4. Estimated
Page 40 and 41: Chapter 2.1 38 DNA was observed in
Page 45 and 46: Cha pter 2.2 Factors that predict r
Page 47 and 48: INTRODUCTION Factors that predict r
Page 49 and 50: Factors that predict response to PE
Page 51 and 52: Table 1. Baseline characteristics a
Page 53 and 54: ��
Page 61: Factors that predict response to PE
Page 64 and 65: Chapter 2.3 62 ABSTRACT Peginterfer
Page 66 and 67: Chapter 2.3 64 only provides the be
Page 68 and 69: Chapter 2.3 66 optimal cut-off poin
Page 70 and 71: Chapter 2.3 68 Table 2. Logistic re
Page 72 and 73: Chapter 2.3 70 and p=0.056 for the
Page 74 and 75: Chapter 2.3 72 DISCUSSION Recently
Page 76 and 77: Chapter 2.3 74 Taqman PCR. A reliab
Page 78: Chapter 2.3 76 13. Robins JM, Herna
Page 82 and 83: Chapter 2.4 80 ABSTRACT Dynamic upd
Page 84 and 85: Chapter 2.4 82 prediction is necess
Page 86 and 87: Chapter 2.4 84 a. b. c. Figure 1.Th
Page 88 and 89: Chapter 2.4 86 suggested above a sm
Page 90 and 91: Chapter 2.4 88 Finally in the rando
Page 92 and 93:
Chapter 2.4 90 more or less no chan
Page 94 and 95:
Chapter 2.4 92 a. b. c. Figure 3. B
Page 96 and 97:
Chapter 2.4 94 Figure 4. Dynamic pr
Page 98 and 99:
Chapter 2.4 96 overall baseline pre
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Chapter 2.4 98 Finally some compari
Page 102 and 103:
Chapter 2.4 100 mixed effect models
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Chapter 2.4 102 References 1. Janss
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Cha pter 2.5 Early on-treatment pre
Page 109 and 110:
INTRODUCTION Early on-treatment pre
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Statistical analysis Early on-treat
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Early on-treatment prediction of re
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Page 117 and 118:
Page 119 and 120:
References Early on-treatment predi
Page 121 and 122:
Page 125:
Cha pter 3 Statistical models of lo
Page 128 and 129:
Chapter 3.1 126 ABSTRACT Background
Page 130 and 131:
Chapter 3.1 128 METHODS Study desig
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Chapter 3.1 130 the presence of a c
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Chapter 3.1 132 ure 2 30 >3 x ULN 2
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Chapter 3.1 134 DISCUSSION The aim
Page 138 and 139:
Chapter 3.1 136 References 1. Poyna
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Chapter 3.1 138 U i = Time to failu
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Chapter 3.2 142 Abstract We have de
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Chapter 3.2 144 multiple markers wa
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Chapter 3.2 146 The correlation bet
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Chapter 3.2 148 for our MLMM is fac
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Chapter 3.2 150 X and Z matrices fr
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Chapter 3.2 152 For each g =0,...,G
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Chapter 3.2 154 Focus of marginal,
Page 158 and 159:
Chapter 3.2 156 Figure 1. Dutch PBC
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Chapter 3.2 158 Table 2. Dutch PBC
Page 162 and 163:
Page 164 and 165:
Page 166 and 167:
Chapter 3.2 164 effects correct the
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Chapter 3.2 166 References 1. Kuipe
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Chapter 3.2 168 32. Tsiatis AA, Dav
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Chapter 3.2 170 Table 4. Structure
Page 177 and 178:
Cha pter 4.1 Viral dynamics during
Page 179 and 180:
INTRODUCTION Viral dynamics during
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V(t) = V 0 { A exp (-λ 1 t ) + (1-
Page 183 and 184:
Table 2. Dynamic parameters during
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Figure 1. Viral dynamics during and
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Viral dynamics during and after ent
Page 189 and 190:
References Viral dynamics during an
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Viral dynamics during and after ent
Page 194 and 195:
Chapter 4.2 192 ABSTRACT Tenofovir,
Page 196 and 197:
Chapter 4.2 194 PATIENTS AND METHOD
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Chapter 4.2 196 2 Slow: decline bet
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Chapter 4.2 198 Table 2. Parameter
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Chapter 4.2 200 9.0 8.0 7.0 6.0 5.0
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Chapter 4.2 202 release. Although w
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Chapter 4.2 204 References 1. Perri
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Chapter 4.2 206 29. Lewin SR, Ribei
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Chapter 4.3 210 ABSTRACT Treatment
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Chapter 4.3 212 HBV DNA quantifi ca
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Chapter 4.3 214 The resulting model
Page 218 and 219:
Chapter 4.3 216 Figure 1. Median HB
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Chapter 4.3 218 Table 2: Pharmacoki
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Chapter 4.3 220 Figure 3. effects r
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Chapter 4.3 222 13-14 This model ta
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Chapter 4.3 224 References 1. Kane
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Chapter 4.3 226 25. Wolters LM, Han
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Cha pter 5 Summary and conclusion
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Summary and conclusion 232 Therapy
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Summary and conclusion 234 who deve
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Summary and conclusion 236 fi t mod
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Cha pter 6 Samenvatting en conclusi
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Samenvatting en conclusie 242 posit
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Samenvatting en conclusie 244 De ve
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Samenvatting en conclusie 246 en na
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Samenvatting en conclusie 248 In ee
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DANKWOORD Dankwoord 253 Met oplucht
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CUR RICULUM VITAE Curriculum Vitae
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Bibliography 258 Mechanical factors
Page 262 and 263:
Bibliography 260 35. Wolters LM, Ha
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Bibliography 262 Volume Measurement
Page 266 and 267:
Bibliography 264 Quantitative HBV D
Page 268 and 269:
Bibliography 266 to Peginterferon-a
Page 272:
ISBN: 978-90-8559-069-9
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