Journal of Hepatology
Volume 56, Issue 5, May 2012, Pages 1006–1011
Research Article
Validation of a stopping rule at week 12 using HBsAg and HBV DNA for HBeAg-negative patients treated with peginterferon alfa-2a- Vincent Rijckborst1,
- Bettina E. Hansen1, 2,
- Peter Ferenci3,
- Maurizia R. Brunetto4,
- Fehmi Tabak5,
- Yilmaz Cakaloglu6,
- A. Galeota Lanza7,
- Vincenzo Messina8,
- Claudio Iannacone9,
- Benedetta Massetto10,
- Loredana Regep11,
- Massimo Colombo12,
- Harry L.A. Janssen1,
 , †,  , - Pietro Lampertico12, †
- 1 Dept. of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
- 2 Dept. of Biostatistics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
- 3 Dept. of Internal Medicine 3, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
- 4 Hepatology Unit, University Hospital Pisa, Pisa, Italy
- 5 Dept. of Infectious Diseases, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey
- 6 Dept. of Gastroenterohepatology, Istanbul University Medical School, Istanbul, Turkey
- 7 Liver Unit, Cardarelli Hospital, Naples, Italy
- 8 Infectious Disease Unit, SS Anna and Sebastiano Hospital, Caserta, Italy
- 9 SPARC Consulting, Milan, Italy
- 10 Roche, Monza, Italy
- 11 Roche, Basel, Switzerland
- 12 First Gastroenterology Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Università di Milano, Milan, Italy
- Received 16 September 2011. Revised 18 November 2011. Accepted 14 December 2011. Available online 13 January 2012.
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Background & AimsIt was recently demonstrated that none of the hepatitis B e antigen (HBeAg)-negative patients without any serum hepatitis B surface antigen (HBsAg) decline and with <2 log hepatitis B virus (HBV) DNA decline at week 12 of a 48-week peginterferon alfa-2a (PEG-IFN) treatment course achieved a sustained response (SR). We aimed at validating this stopping rule in two independent trials. MethodsHBeAg-negative patients receiving 48 or 96 weeks of PEG-IFN in the phase III registration trial (N = 85) and PegBeLiver study (N = 75) were stratified according to the presence of any HBsAg decline and/or ⩾2 log HBV DNA decline at week 12. SR was defined as HBV DNA <2000 IU/ml and normal alanine aminotransferase 24 weeks after treatment. ResultsThe original PARC trial included 102 patients (genotype A/D/other: 14/81/7), 25 (25%) had an SR. The validation dataset consisted of 160 patients (genotype A/B/C/D/other: 10/18/34/91/7), 57 (36%) achieved an SR. The stopping rule performed well across the two studies (p = 0.001) and its negative predictive value [NPV] was 95% in the validation dataset harbouring genotypes A–D. Its performance was best for genotype D. Moreover, among the 34 patients treated for 96 weeks, none of the 7 (21%) without HBsAg decline and with <2 log HBV DNA decline at week 12 achieved an SR (NPV 100%). ConclusionsWe confirmed in two independent studies that the combination of HBsAg and HBV DNA levels at week 12 identifies HBeAg-negative patients with a very low chance of SR to either 48 or 96 weeks of PEG-IFN therapy.
Abbreviations- HBeAg, hepatitis B e antigen;
- CHB, chronic hepatitis B;
- NA, nucleos(t)ide analogues;
- HBV, hepatitis B virus;
- PEG-IFN, peginterferon;
- SR, sustained response;
- HBsAg, hepatitis B surface antigen;
- ALT, alanine aminotransferase;
- ULN, upper limit of normal;
- PCR, polymerase chain reaction;
- ANOVA, analysis of variance;
- NPV, negative predictive value;
- PPV, positive predictive value
Keywords- HBV therapy;
- Immunomodulator;
- Nucleos(t)ide analogues;
- Peginterferon;
- Quantitative HBsAg;
- HBV genotype
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发表于 2012-4-14 19:25
