Virologic Relapse following Treatment Induced Hepatitis B e Antigen Seroconversion in Chronic Hepatitis B (CHB) Patients

Abstract

Purpose: The treatment goal for hepatitis B e antigen (HBeAg) positive patients is HBeAg seroconversion; however, this endpoint may not be durable following discontinuation of antiviral therapy. Our goal was to examine the rate of relapse in these patients. Methods: We retrospectively studied 52 consecutive CHB patients who achieved treatment-induced seroconversion (out of 396 patients treated for a median duration of 18 months). Our cohort consists of patients who maintained on therapy (n=28) and who discontinued therapy (n=24) between January 2001 and November 2009 at 2 community U.S. GI clinics. HBeAg seroconversion is defined as conversion of HBeAg-positive to HBeAg-negative and development of hepatitis B e antibody (anti-HBe). Virologic relapse is defined as reappearance of detectable HBV DNA by PCR testing (>60-100 IU/mL). Results: All patients were Asians and predominantly male (67%). Antiviral medication in which patients achieved seroconversion were lamivudine (17%), adefovir dipivoxil (40%), entecavir (35%), tenofovir (4%), and entecavir+tenofovir (4%). Median treatment duration after seroconversion to treatment discontinuation was 12 (1-41) months, in which all patients had undetectable serum HBV DNA (<60-100 IU/mL) and normal ALT (≤40 U/L). Following seroconversion, 71% of patients received another 12 months or more of therapy prior to discontinuation, 17% with another 6-12 months of therapy, and only 12% having less than 6 months of consolidation therapy. At time of seroconversion, patients who were maintained on therapy had significantly higher HBV DNA (1.36±1.97 vs. 0.33±0.86, p=0.03) and median ALT (33 [11-85] vs. 24 [8-60], p=0.04) compared to patients who discontinued therapy. Median age at seroconversion was similar in both cohorts (39 [19-58] vs. 38 [13-68], p=0.53). Virologic relapse occurred in 23 of 24 patients (96%) who discontinued therapy compared to 0 of 28 patients (0%) who maintained on treatment, p<0.0001. For patients who ceased treatment, the time to relapse was 3 (1-42) months. Conclusion: After achieving HBeAg seroconversion, the majority of patients who discontinued antiviral therapy relapsed with reappearance of viremia. Patients should be monitored closely for relapse when therapy is discontinued, even after HBeAg seroconversion.