Hepatitis B surface antigen: association with sustained response to peginterferon alfa-2a in hepatitis B e antigen-positive patients

Abstract

Patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, who achieve HBeAg seroconversion 6months after completing 48weeks of peginterferon alfa-2a therapy, have an increased chance of clearing hepatitis B surface antigen (HBsAg) during long-term treatment-free follow-up. This analysis aimed to determine whether HBsAg quantification during treatment could be used to identify posttreatment response. Patients (n=399) treated with peginterferon alfa-2a (180μg/week) alone or in combination with lamivudine (100mg/day) for 48weeks during a large, randomized study were included in this retrospective analysis. Receiver-operating characteristic analyses were used to identify baseline and on-treatment HBsAg levels associated with response (HBeAg seroconversion 6months posttreatment). Baseline HBsAg levels were lower in patients achieving posttreatment response than in nonresponders (3.97 and 4.21IU/mL, respectively, p=0.039). Two baseline HBsAg cutoff levels (5,000 and 50,000IU/mL) provided a positive predictive value of 42% and a negative predictive value of 77%. HBsAg decline was significantly greater during and posttreatment in responders than in nonresponders (p<0.0001). HBeAg seroconversion rates 6months posttreatment were significantly higher in patients with HBsAg<1,500IU/mL at weeks 12 and 24 (56.7 and 54.4%, respectively) versus patients with HBsAg 1,500-20,000IU/mL (32.3 and 26.1%, respectively) or HBsAg<20,000IU/mL (16.3 and 15.4%, respectively) (all p<0.0001 and <0.0001). HBsAg levels at baseline strongly associated with posttreatment response were not identified. Low HBsAg levels during peginterferon alfa-2a therapy were associated with high rates of posttreatment response. On-treatment HBsAg quantification may, therefore, help guide patient management in the future.