High Rate of Recurrent Hepatitis B Viremia Following Treatment-Induced Hepatitis B E Antigen (HBeAg) Seroconversion

Abstract

Purpose: In patients with HBeAgpositive chronic hepatitis B (CHB), one of the primary endpoints of therapy is HBeAg seroconversion; however, there is inconsistent data on the durability of HBeAg seroconversion following consolidation therapy. Our goal is to investigate the rate of recurrent HBV viremia in CHB patients after HBeAg seroconversion. Methods: We retrospectively studied 88 consecutive CHB patients who achieved treatment-induced HBeAg seroconversion among the 458 HBeAg-positive patients treated with various antiviral regimens at 3 GI and liver clinics in the U.S. between 3/1998 and 9/2010. HBeAg seroconversion was defined as loss of HBeAg and development of hepatitis B e antibody (anti-HBe). Recurrent HBV viremia was defined as reappearance of detectable HBV DNA (>100 IU/mL) from nadir in two consecutive laboratory tests. Results: Patients were stratified into two groups: Group I 49 patients who remained on therapy, and Group II 39 patients who discontinued therapy following HBeAg seroconversion. In both groups, the majority of patients were Asian (94-95%) and male (62-69%). Antiviral medications in which patients achieved HBeAg seroconversion included: lamivudine (23%), adefovir (34%), entecavir (36%), tenofovir (4%), adefovir+lamivudine (1%), and entecavir+tenofovir (2%). Median treatment duration before HBeAg seroconversion was similar in Group I and Group II (18 [1-86] vs. 21 [5-63] months, p=0.99). At the time of HBeAg seroconversion, compared to Group I, Group II was younger (37±10 vs. 41±12 years), had lower mean HBV DNA levels (0.27±0.78 vs. 0.95±1.69 log10 IU/mL), and median ALT levels (24 [8-60] vs. 30 [593] U/L). In Group II, the median duration of consolidation therapy before treatment discontinuation was 12 months (range, 1-55), in which 10 completed <6 months, 10 completed 6-11 months, and 19 completed ≥12 months. At time of treatment discontinuation, all patients in Group II had undetectable HBV DNA. The rate of recurrent HBV viremia was significantly higher in Group II compared to Group I (90% vs. 0%, p<0.0001). After a median of 3 (1-42) months off therapy, the mean HBV DNA level detected at time of recurrent HBV viremia was 4.11±1.92 log10 IU/mL. Conclusion: The majority of patients (90%) who discontinued therapy after achieving HBeAg seroconversion with undetectable HBV DNA by PCR experienced recurrent HBV viremia. Patients who remained on therapy achieved and maintained undetectable level of HBV DNA. Patients should be monitored closely for recurrent HBVwhen therapy is discontinued, despite achieving HBeAg seroconversion.