Greater HBV Suppression with Lamivudine (Epivir-HBV) +/- Peginterferon Alfa-2a (Pegasys) Does Not Translate into Improved Rates of Sustained HBeAg Seroconversion
It remains unclear whether HBV-DNA must be suppressed by a certain amount or below a specific level in order to achieve HBeAg seroconversion. Furthermore, the optimal duration of HBV-DNA suppression, before and after HBeAg seroconversion, that will sustain seroconversion remains unknown.
The aim of the current study was to evaluate the association between on-treatment viral suppression and (1) HBeAg seroconversion and (2) YMDD mutation development in patients with HBeAg-positive chronic HBV enrolled in a large, randomised, multinational study of peginterferon alfa-2a (Pegasys) alone, peginterferon alfa-2a plus lamivudine, and lamivudine (Epivir-HBV) alone.
HBeAg-positive patients (n=814) received (1:1:1) either peginterferon alfa-2a (180μg once-weekly) + placebo, peginterferon alfa-2a + lamivudine (100mg once-daily) or lamivudine alone. Patients were treated for 48 weeks and assessed after 24 weeks of follow-up (week 72). HBV-DNA was measured with COBAS-AMPLICOR HBV MONITOR®; YMDD mutants with the INNO-LiPA HBV DR assay.
Result
The relationship between end-of-treatment HBV-DNA response, occurrence of YMDD mutants and sustained HBeAg seroconversion are presented in the Table below.
Conclusions
Mean HBV-DNA suppression was greater with peginterferon alfa-2a plus lamivudine and lamivudine monotherapy compared to peginterferon monotherapy (see Table).
“However,” write the authors, “HBeAg seroconversion rates 24 weeks after the end of treatment were highest with peginterferon alfa-2a monotherapy, suggesting that that more potent HBV-DNA suppression does not necessarily translate into improved HBeAg seroconversion rates.”
In addition, they note, “Increased HBV-DNA suppression with combination therapy resulted in a lower incidence of YMDD mutation than seen with lamivudine alone.”
1University of North Carolina Liver Program, University of North Carolina, Chapel Hill NC, USA
2Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China
3Department of Medicine, Songklanakarin Hospital, Songkla, Thailand
4Department of Infectious Diseases, Nangfang Hospital, Guangzhou, China
5Gastroenterology Department, Singapore General Hospital, Singapore, Singapore
6Department of Gastroenterology, Samsung Medical Center, Seoul, South Korea
7Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
8Department of Infectious Diseases, Medical University of Bialystock, Bialystock, Poland
9Roche, Welwyn, UK
10Medizinische Klinik M.S. Hepatologie und Gastroenterologie, Charité, Humboldt Universität zu Berlin, Berlin, Germany | 
发表于 2005-4-21 02:04
