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High Frequency of Recurrent Viremia After Hepatitis B e Antigen Seroconversion and Consolidation Therapy

Chaung, Kevin T. BS*,†; Ha, Nghiem B. BS*,†; Trinh, Huy N. MD*,‡; Garcia, Ruel T. MD; Nguyen, Huy A. MD; Nguyen, Khanh K. MD; Garcia, Gabriel MD; Ahmed, Aijaz MD; Keeffe, Emmet B. MD†,✠; Nguyen, Mindie H. MD, MAS

doi: 10.1097/MCG.0b013e31825ceed9
LIVER, PANCREAS AND BILIARY TRACT: Original Articles

Background: The primary treatment endpoint for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is HBeAg seroconversion; however, data on the durability of response are inconsistent.

Goals: Our goal was to investigate the rate of recurrent viremia after HBeAg seroconversion and subsequent discontinuation of therapy.

Methods: We retrospectively studied 88 consecutive Asian American patients who achieved HBeAg seroconversion [loss of HBeAg and development of antibody to HBeAg (anti-HBe)] among 458 HBeAg-positive patients who received oral antiviral therapy at 3 US clinics between March 1998 and November 2010. Recurrent viremia was defined as reappearance of detectable serum hepatitis B virus DNA (>100 IU/mL) on 2 consecutive laboratory tests from previously undetectable levels.

Results: Antiviral medications used at the time of HBeAg seroconversion included: lamivudine (23%), adefovir (34%), entecavir (36%), tenofovir (4%), and combination therapy (3%). Antiviral therapy was continued after HBeAg seroconversion in 49 patients (group I) and discontinued in the other 39 patients after consolidation therapy [median=12 months (range, 1 to 55 mo)] (group II). No patients in group I experienced recurrent viremia, whereas 90% in group II did. Elevated alanine aminotransferase also occurred in 38% of group II patients [median peak alanine aminotransferase 249 IU/mL (range, 93 to 1070 IU/mL)].

Conclusions: Despite consolidation therapy, almost all patients who discontinued therapy after achieving HBeAg seroconversion and complete viral suppression experienced recurrent viremia, and close to half also experienced biochemical flares. HBeAg seroconversion does not seem to be a durable treatment endpoint for many patients, and they should be monitored carefully for virologic relapse and biochemical flares if antiviral therapy is withdrawn.

*Pacific Health Foundation

San Jose Gastroenterology, San Jose

Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA

✠ Deceased.

Kevin T. Chaung, Nghiem B. Ha, Khanh K. Nguyen and Gabriel Garcia have no financial relationship with a commercial interest. Huy N. Trinh has a financial relationship with – Gilead Sciences: grant/research support, speaking and teaching, advisory committees/review panels, stock and shareholder; Bristol-Myers Squibb: grant/research support, advisory committees/review panels; Vertex Pharmaceuticals: speaking and teaching. Ruel T. Garcia has a financial relationship with – Bristol-Myers Squibb: speaking and teaching. Huy A. Nguyen has a financial relationship with – Gilead Sciences: speaking and teaching. Aijaz Ahmed has a financial relationship with – Bristol-Myers Squibb: consulting; Gilead Sciences: consulting, grant/research support; Hoffman-LaRoche: consulting; Romark Laboratories: grant/research support; Salix Pharmaceuticals: advisory committees/review panels; Schering-Plough: advisory committees/review panels; Vertex Pharmaceuticals: advisory committees/review panels; Three Rivers Pharmaceuticals: advisory committees/review panels. Emmet B. Keeffe had a financial relationship with - Bristol-Myers Squibb: consulting, speaking, and teaching; Hyperion Therapeutics: advisory committees/review panels; Vertex Pharmaceuticals: employee. Mindie H. Nguyen has a financial relationship with – Gilead Sciences: consulting; Bristol-Myers Squibb: consulting, grant/research support; Novartis Pharmaceuticals: grant/research support; Roche Pharma AG: grant/research support; Bayer AG: consulting.

Financial Disclosures: No funding to disclose.

Reprints: Mindie H. Nguyen, MD, MAS, Division of Gastroenterology and Hepatology, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA 94304 (e-mail: mindiehn@stanford.edu).

Received January 11, 2012

Accepted April 30, 2012

© 2012 Lippincott Williams & Wilkins, Inc.