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 ? log HBV DNA decline at week 12. SR was defined as HBV DNA <2000 IU/ml and normal alanine aminotransferase 24 weeks after treatment.
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 % ).
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.