Sonneveld MJ, Rijckborst V, Zeuzem S, Heathcote EJ, Simon K, Senturk H, Pas SD, Hansen BE, Janssen HL.
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Peginterferon (PEG-IFN) treatment of HBeAg-positive chronic hepatitis B (CHB) results in HBeAg loss in 30% of patients, but clearance of HBV DNA and HBsAg from serum is less often achieved. We investigated whether the presence of precore (PC) and basal core promoter (BCP) mutants before PEG-IFN treatment affects serological and virological response. A total of 214 HBeAg-positive CHB patients treated with PEG-IFN±lamivudine for 52 weeks in a global randomized trial were classified at baseline as wildtype (WT) or non-WT (detectable mutants at PC/BCP) by line-probe assay. Response was assessed at 6 months post-treatment and through long-term follow-up(LTFU). Mutants were detected in 64% of patients, in varying frequencies across HBV genotypes A through D. Patients with WT had higher baseline HBV DNA, HBeAg and HBsAg levels than patients with non-WT. Patients with WT were more likely to achieve HBeAg loss with HBV DNA<10,000 copies/mL (response, 34 versus 11%,p<0.001) and HBsAg clearance (18 versus 2%,p<0.001) at week 78 than non-WT patients. Among WT patients who achieved HBeAg clearance at week 78, 78% had undetectable HBV DNA and 61% achieved HBsAg clearance at LTFU (versus 26% and 15% in non-WT patients,p<0.001 for both). Presence of WT virus at baseline was an independent predictor of response (OR 2.90, 95%CI:1.15-7.31,p=0.023) and HBsAg clearance (OR 5.58, 95%CI:1.26-24.63,p=0.013) and patients with non-A genotypes with detectable mutants had a low probability of response. CONCLUSION: Presence of only WT virus at baseline is a strong predictor of response (HBeAg loss with HBV DNA <10,000 copies/mL) to PEG-IFN for HBeAg-positive CHB. Patients with detectable PC and/or BCP mutants have a lower probability of response and are less optimal candidates for PEG-IFN therapy. (HEPATOLOGY 2012.).