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Chapter 4.1 186 suppression in serum. The latter explanation has previously been used as an explanation for the slower return of viral replication after withdrawal of lamivudine therapy. 28 In conclusion, these data show that both decay of viral concentration as well as rebound of hepatitis B viral concentration can be fi tted with a mathematical model. Entecavir is effective in patients infected with wildtype and variant HBV. In the future, data on the actual amount of cccDNA in the liver of these entecavir-treated patients could be helpful in supporting the outcome of the parameter estimates.
References Viral dynamics during and after entecavir therapy 187 1. Bortorelli F, Cadrobbi P, Crivellaro C, Guido M, Rugge M, Noventa F, et al. Long-term outcome of chronic type B hepatitis in patients who acquire hepatitis B virus infection in childhood. Gastroenterol ogy 1990;99:805–810. 2. Realdi G, Alberti A, Rugge M, Bortolotti F, Tigoli AM, Tremolada F, et al. Seroconversion from hepatitis B e antigen to anti HBe in chronic hepatitis B virus infection. Gastroenterology 1980;79:195–199. 3. Hoofnagle JH, Dusheiko GM, Seef LB, Jones EA, Waggoner JG, Bales ZB. Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis. Ann Intern Med 1981;94:744–748. 4. Wong DK, Cheung AM, O’Rourke K, Naylor CD, Detsky AS, Heath-cote J. Effect of alphainterferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B: a meta-analysis. Ann Intern Med 1993;119:312–323. 5. Krogsgaard K, Bindslev N, Christensen E, Craxi A, Schlichting P, Schalm S, et al. The treatment effect of alpha interferon in chronic hepatitis B is independent of pre-treatment variables. Results based on individual patient data from 10 clinical controlled trials. European Concerted Action on Viral Hepatitis (EUROHEP). J Hepatol 1994;21:646–655. 6. Schiff E, Cianciara J, Karayalcin S, Kowdley K, Woessner M, McMullen S, et al. Durable HBeAg and HBsAg seroconversion after lamivudine for chronic hepatitis B (CHB) (abstract). J Hepatol 2000;2:99. 7. Song BC, Suh DJ, Lee HC, Chung YH, Lee YS. Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea. Hepatology 2000;32:803–806. 8. Fontaine H, Driss F, Lagneau JL, Zylberberg H, Brechot C, Pol S. Hepatitis B virus reactivation after lamivudine discontinuation (abstract). Hepatology 1999;30(Suppl):349. 9. Moraleda G, Spautelli J, Aldrich CE, Averett D, Condreay L, Mason W. Lack of effect of antiviral therapy in nondividing hepatocyte cultures on the closed circular DNA of woodchuck hepatitis B virus. J Virol 1997;71:9392–9399. 10. Delaney W, Miller T, Isom HC. Use of the hepatitis B virus recombinant baculovirus-HepG2 system to study the effects of (-)-β-2’-3’-dideoxy-3’-thiacytidine on the replication of hepatitis B virus and accumulation of covalently closed circular DNA. Antimicrob Agents Chem 1999;43:2017–2026. 11. Innaimo SF, Seifer M, Bisacchi G, Standring D, Zahler R, Colonno RJ. Identification of BMS- 200.475 as a potent and selective inhibitor of hepatitis B virus. Antimicrob Agents Chem 1997;41:1444–1448. 12. Yamanaka G, Wilson T, Innaimo S, Bisacchi G, Egli P, Rinehart JK, et al. Metabolic studies on BMS-200475, a new antiviral compound active against hepatitis B virus. Antimicrob Agents Chem 1999;43:190–193.
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Statistical Models of Treatment Eff
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ISBN: 978-90-8559-069-9 © Bettina
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PROMOTIECOMMISSIE Promotor: Prof.dr
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CONTENTS Chapter 1. Introduction 11
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Cha pter 1 Introduction
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Chapter 1 14 Epidemiology Worldwide
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Chapter 1 16 Prediction models with
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Chapter 1 18 standard method fails
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Chapter 1 20 The extended non-linea
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Chapter 1 22 References 1. Blumberg
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Cha pter 2 Prediction of response t
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Chapter 2.1 28 ABSTRACT The aim of
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Chapter 2.1 30 been hepatitis B sur
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Chapter 2.1 32 HBV DNA decline The
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Chapter 2.1 34 Figure 2 continued.
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Chapter 2.1 36 Figure 4. Estimated
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Chapter 2.1 38 DNA was observed in
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Chapter 2.1 40 15. Kao JH. Role of
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Chapter 2.2 44 ABSTRACT Background:
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Chapter 2.2 46 low baseline HBV DNA
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Chapter 2.2 48 patient subgroups wa
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Chapter 2.2 50 p=0.002). Previous I
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Chapter 2.2 52 Application of the m
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Chapter 2.2 54 PEG-IFN, the proport
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Chapter 2.2 56 References 1. Lavanc
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Chapter 2.2 58 26. Bonino F, Lau GK
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Chap ter 2.3 Prediction of the resp
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INTRODUCTION Dynamic prediction of
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Statistical analysis Dynamic predic
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Dynamic prediction of response to P
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References Dynamic prediction of re
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Cha pter 2.4 Dynamic prediction of
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INTRODUCTION Dynamic prediction of
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For the indirect approach we rewrit
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logit pi,j = logit Pr(Ri =1|visit =
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Dynamic prediction of response usin
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Table 1. Results of different stopp
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Chapter 2.5 106 ABSTRACT Peginterfe
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Chapter 2.5 108 and placebo daily.
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Chapter 2.5 110 for patients with a
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Chapter 2.5 112 Mean HBV DNA declin
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Chapter 2.5 114 peginterferon and n
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Chapter 2.5 116 hepatocellular carc
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Chapter 2.5 118 13. Werle-Lapostoll
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Chapter 2.5 120 Greece - G Germanid
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Chap ter 3.1 Long-term clinical out
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INTRODUCTION Glycyrrhizin for IFN-n
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Statistics Glycyrrhizin for IFN-non
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Glycyrrhizin for IFN-non responders
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Table 2. Time dependent Cox regress
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Page 143 and 144: Cha pter 3.2 Discriminant analysis
Page 145 and 146: Introduction Discriminant analysis
Page 147 and 148: Discriminant analysis using a MLMM
Page 149 and 150: Estimation Discriminant analysis us
Page 153 and 154: where wi,k(y i, θ) = (k =1,...,K).
Page 171 and 172: Appendix Discriminant analysis usin
Page 175: Cha pter 4 Statistical models of ea
Page 178 and 179: Chapter 4.1 176 ABSTRACT Nucleoside
Page 180 and 181: Chapter 4.1 178 at day 1 at t =0 an
Page 182 and 183: Chapter 4.1 180 Table 1. Baseline c
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Page 186 and 187: Chapter 4.1 184 Figure 1. Viral dec
Page 190 and 191: Chapter 4.1 188 13. Seifer M, Hamat
Page 193 and 194: Cha pter 4.2 Viral dynamics during
Page 195 and 196: INTRODUCTION Viral dynamics during
Page 197 and 198: Viral dynamics during tenofovir the
Page 201 and 202: log HBV DNA (copies/mL) 10.0 9.0 8.
Page 211 and 212: Chap ter 4.3 Modelling of early vir
Page 213 and 214: INTRODUCTION HBV viral kinetics dur
Page 215 and 216: HBV viral kinetics during PEG-IFN 2
Page 229: HBV viral kinetics during PEG-IFN 2
Page 233 and 234: SUMMARY AND CONCLUSION Summary and
Page 235 and 236: Summary and conclusion 233 The mode
Page 237 and 238: Summary and conclusion 235 The infe
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Summary and conclusion 237 Early st
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SAMENVATTING EN CONCLUSIE Samenvatt
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Samenvatting en conclusie 243 Er we
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Samenvatting en conclusie 245 Data
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Samenvatting en conclusie 247 Behan
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Dan kwoord
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Dankwoord 254 Lieve Marion en Margr
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BIBLI OGRAPHY Bibliography 257 1. K
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Bibliography 259 Interferon-ribavir
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Bibliography 261 Long term clinical
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Bibliography 263 Flares in chronic
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Bibliography 265 Genetic characteri
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Bibliography 267 106. Reijnders JG,
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