Early serum HBsAg drop: a strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients.

UNLABELLED: Pegylated interferon alfa-2a (PEG-IFN) may induce sustained virological response (SVR) in 20% of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. In addition, loss of hepatitis B surface antigen (HBsAg) is achieved with a 10% yearly rate after treatment cessation in sustained responders. The aim of this study was to assess on-treatment serum HBsAg kinetics to predict SVR in HBeAg-negative patients treated with PEG-IFN. Forty-eight consecutive patients were treated with PEG-IFN (180 microg/week) for 48 weeks. Serum hepatitis B virus (HBV) DNA (COBAS TaqMan) and HBsAg (Abbott Architect HBsAg QT assay) were assessed at baseline, during treatment (weeks 12, 24, and 48), and during follow-up (weeks 72 and 96). SVR was defined as undetectable serum HBV DNA (<70 copies/mL) 24 weeks after treatment cessation. Twenty-five percent of patients achieved SVR. They were not different from those who failed treatment regarding age, sex, ethnicity, HBV genotype, baseline serum HBV DNA and HBsAg levels, or liver histology. During treatment, serum HBsAg levels decreased only in patients who developed SVR, with mean decreases of 0.8 +/- 0.5, 1.5 +/- 0.6, and 2.1 +/- 1.2 log(10) IU/mL at weeks 12, 24, and 48, respectively. A decrease of 0.5 and 1 log(10) IU/mL in serum HBsAg levels at weeks 12 and 24 of therapy, respectively, had high predictive values of SVR (negative predictive value [NPV] 90%, positive predictive value [PPV] 89% for week 12; NPV 97%, PPV 92% for week 24). HBsAg loss was observed in three patients, all with SVR. CONCLUSION: Early serum HBsAg drop has high predictive values of SVR to PEG-IFN in HBeAg-negative CHB patients. Serum quantitative HBsAg may be a useful tool to optimize the management of PEG-IFN therapy in these patients.

Influence of genotype on hepatitis B surface antigen kinetics in hepatitis B e antigen-negative patients treated with pegylated interferon-alpha2a.

BACKGROUND: The aim of this study was to assess the influence of hepatitis B virus (HBV) genotypes on serum hepatitis B surface antigen (HBsAg) kinetics in hepatitis B e antigen (HBeAg)-negative patients treated with pegylated interferon-alpha2a (PEG-IFN-alpha2a). METHODS: A total of 48 consecutive patients treated with PEG-IFN-alpha2a (180 microg/week) for 48 weeks were assessed. HBV genotype was determined. Serum HBV DNA and HBsAg were assessed at baseline, during treatment (weeks 12, 24 and 48) and during follow-up (weeks 72 and 96). RESULTS: The distribution of HBV genotype was A 27%, B 17%, C 12%, D 29% and E 14%. Mean +/-sd pretreatment serum HBV DNA (6.9 +/-1.5 log(10) copies/ml) was not different between genotypes and decreased under treatment in all genotypes without significant difference. Mean +/-sd pretreatment serum HBsAg (3.6 +/-0.6 log(10) IU/ml) was significantly different between genotypes (P<0.001), with high levels in genotypes A and C, intermediate levels in genotypes D and E, and low levels in genotype B (4.0 +/-0.3, 4.1 +/-0.7, 3.6 +/-0.5, 3.6 +/-0.4 and 2.7 +/-0.6 log(10) IU/ml, respectively). Serum HBsAg decreased under treatment in all genotypes with a significant difference. At the end of treatment, mean +/-sd decrease was high in genotype A, intermediate in genotypes B and D, and low in genotypes C and E (1.3 +/-1.6, 0.7 +/-0.7, 0.6 +/-0.9, 0.4 +/-1.0 and 0.4 +/-0.9 log(10) IU/ml, respectively; P<0.001). During follow-up, serum HBsAg continued to decrease in genotypes A and D, whereas rebound was observed in genotypes B, C and E. CONCLUSIONS: HBV genotype has a strong influence on serum HBsAg kinetics during PEG-IFN-alpha2a therapy in HBeAg-negative patients.