Validation of a stopping rule at week 12 using HBsAg and HBV DNA for HBeAg-negative patients treated with peginterferon alfa-2a

• Published in: Journal of hepatology Vol. 56; no. 5; pp. 1006 - 1011
• Main Authors: Rijckborst, Vincent, Hansen, Bettina E, Ferenci, Peter, Brunetto, Maurizia R, Tabak, Fehmi, Cakaloglu, Yilmaz, Lanza, A. Galeota, Messina, Vincenzo, Iannacone, Claudio, Massetto, Benedetta, Regep, Loredana, Colombo, Massimo, Janssen, Harry L.A, Lampertico, Pietro
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.05.2012; Elsevier
• Subjects: Adult; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - therapeutic use; Biological and medical sciences; Biomarkers - blood; DNA, Viral - blood; Dose-Response Relationship, Drug; Female; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Genotype; HBV genotype; HBV therapy; Hepatitis B - blood; Hepatitis B - drug therapy; Hepatitis B Surface Antigens - blood; Hepatitis B virus - genetics; Humans; Immunomodulator; Immunomodulators; Interferon-alpha - therapeutic use; Male; Medical sciences; Middle Aged; Nucleos(t)ide analogues; Peginterferon; Pharmacology. Drug treatments; Polyethylene Glycols - therapeutic use; Predictive Value of Tests; Quantitative HBsAg; Recombinant Proteins - therapeutic use; Retrospective Studies; Time Factors; Treatment Outcome; Withholding Treatment; positive predictive value; HBV genotype; hepatitis B virus; alanine aminotransferase; ALT; hepatitis B e antigen; peginterferon; analysis of variance; ANOVA; NPV; ULN; HBV therapy; PPV; PEG-IFN; HBV; polymerase chain reaction; SR; chronic hepatitis B; hepatitis B surface antigen; HBeAg; HBsAg; Immunomodulator; upper limit of normal; NA; Quantitative HBsAg; sustained response; nucleos(t)ide analogues; CHB; PCR; negative predictive value; Nucleos(t)ide analogues; Peginterferon; Antineoplastic agent; Human; Hepatitis B surface antigen; Typing; Cytokine; Genotype; Microbiological investigation; Interferon alpha 2a; Peginterferon alfa-2a; Treatment; DNA; Gastroenterology; Antiviral; Pegylated form; Quantitative analysis
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2011.12.007

Background & Aims It 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. Methods HBeAg-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. Results The 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%). Conclusions We 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.