Gastroenterology

Gastroenterology

Volume 139, Issue 2, August 2010, Pages 491-498
Gastroenterology

Clinical—Liver, Pancreas, and Biliary Tract
Nucleos(t)ide Analogues Only Induce Temporary Hepatitis B e Antigen Seroconversion in Most Patients With Chronic Hepatitis B

https://doi.org/10.1053/j.gastro.2010.03.059Get rights and content

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.

Section snippets

Study Population

All adult patients with chronic HBV infection (HBsAg-positivity for at least 6 months), referred to the Erasmus Medical Center between 1996 and 2009, who were treated with nucleos(t)ide analogue therapy for at least 6 months, and who tested HBeAg positive, antibody against HBeAg (anti-HBe) negative at the start of treatment, were eligible. Major exclusion criteria were as follows: co-infection with hepatitis C virus, hepatitis D virus, or human immunodeficiency virus, and treatment with

Results

Baseline characteristics of all patients are shown in Table 1. A total of 132 patients with chronic HBV infection treated with nucleos(t)ide analogues in our hospital were included for analysis. Overall, 67 patients were treated with LAM monotherapy, 33 with adefovir (ADV), 22 with entecavir, 6 with tenofovir, 2 with ADV–LAM combination therapy, and 2 with tenofovir-LAM. A total of 117 (89%) patients were nucleos(t)ide analogue treatment-naive, whereas 15 (11%) subjects had been treated

Discussion

Our study explores the long-term durability of nucleos(t)ide analogue-induced HBeAg seroconversion. During a median follow-up period of 5 years after the development of nucleos(t)ide analogue-induced HBeAg seroconversion, only 31% of patients showed a durable remission, defined as HBeAg negativity and HBV-DNA levels less than 10,000 copies/mL. Moreover, sustained response was shown in just 2 of 9 patients who discontinued therapy after a consolidation therapy of at least 6 months. On-treatment

Acknowledgments

The authors thank the Department of Virology, Erasmus MC University Medical Center Rotterdam, for performing virologic testing, and Professor Wang, Department of Gastroenterology, Zong Shan Hospital, Fudan University, Shanghai, China, for her contribution to the manuscript.

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    Conflicts of interest These authors disclose the following: Jurriën Reijnders has received speaker's honoraria from Novartis and Bristol-Myers Squibb; Harry Janssen has received research support and consulting fees from Bristol-Myers Squibb, Gilead, Novartis, and Roche, and research support from Schering-Plough. The remaining authors disclose no conflicts.

    Funding Dr Janssen is a clinical fellow and Vidi laureate of The Netherlands Organisation for Scientific Research.

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