Background & Aims: Inconsistencies in results and guideline recommendations regarding the durability of nucleos(t)ide analogue-induced hepatitis B e antigen (HBeAg) seroconversion require clarification. We studied the long-term durability of nucleos(t)ide analogue-induced HBeAg seroconversion in patients with chronic hepatitis B virus (HBV) infection. Methods: We performed a single-center cohort study of 132 HBeAg-positive patients who had received nucleos(t)ide analogue therapy. Results: During a median treatment duration of 26 months (range, 16-43 mo), HBeAg seroconversion occurred in 46 of 132 subjects (35%). Forty-two subjects (91%) had follow-up evaluation after HBeAg seroconversion. During a median follow-up period of 59 months (range, 28-103 mo) after HBeAg seroconversion, 13 of 42 patients (31%) showed a durable remission (defined as HBeAg negative and HBV-DNA level <10,000 copies/mL). Overall, 33 of 42 subjects (79%) continued therapy after HBeAg seroconversion; of these, 22 (67%) showed serologic and/or virologic recurrence. Nine of 42 subjects (21%) discontinued therapy after HBeAg seroconversion and at least 6 months of consolidation therapy. Only 2 patients showed a durable response in the absence of therapy. Disease recurrence in patients who continued therapy after HBeAg seroconversion was preceded by the development of resistance (80% of these patients); resistance only occurred in subjects given lamivudine monotherapy. In contrast, recurrence after treatment discontinuation or noncompliance was observed in all patients given nucleos(t)ide analogues. Conclusions: Induction of HBeAg seroconversion by nucleos(t)ide analogues is temporary in most patients with chronic HBV infection. Long-term continuation of nucleos(t)ide analogue treatment, irrespective of the occurrence of HBeAg seroconversion, appears to be necessary.

Antiviral Therapy, Asian, Caucasian, Discontinuation, Durability, Hepatitis B virus, Kaplan Meier method, Sustained Response, adefovir, adult, alanine aminotransferase, alanine aminotransferase blood level, antiviral resistance, antiviral therapy, antivirus agent, article, assessment, bioassay, biological marker, blood, clinical evaluation, cohort analysis, drug administration, drug withdrawal, entecavir; hepatitis B surface antigen, enzyme immunoassay, female, follow up, genetics, genotype, hepatitis B, hepatitis B(e) antibody, hepatitis B(e) antigen, human, immunology, lamivudine, major clinical study, male, middle aged, monotherapy, nucleoside, nucleoside derivative, nucleotide, outcome assessment, patient compliance, priority journal, proportional hazards model, real time polymerase chain reaction, recurrence risk, recurrent disease, remission, risk , seroconversion, serology, tenofovir, time, treatment duration, treatment outcome, treatment response, virus DNA, virus load,
Erasmus MC: University Medical Center Rotterdam

Reijnders, J.G.P, Perquin, M.J, Zhang, N, Hansen, B.E, & Janssen, H.L.A. (2010). Nucleos(t)ide analogues only induce temporary hepatitis B e antigen seroconversion in most patients with chronic hepatitis B. Gastroenterology, 139(2), 491–498. doi:10.1053/j.gastro.2010.03.059