Sustained
Response in HBeAg Negative Chronic Hepatitis B Patients 3 Years After Treatment
with Pegasys By
Liz Highleyman Investigators
with the international Peginterferon alfa-2a in HBeAg-negative Chronic Hepatitis
B Study Group randomly assigned more than 500 HBeAg negative chronic hepatitis
B patients to received 180 mcg/week pegylated interferon monotherapy, 100 mg/day
lamivudine (Epivir) monotherapy, or the same doses
of both drugs used in combination, all for 48 weeks. The
researchers previously reported that HBeAg negative patients treated with pegylated
interferon, with or without lamivudine, achieved significantly higher rates of
sustained response 6 months after completing therapy than individuals treated
with lamivudine alone. In
the present analysis, the authors looked at long-term durability though 3 years
after treatment completion. A total of 315 patients (59% of the original patient
population) participated in the post-treatment observational study. Results  | 3
years after treatment, 28% of patients treated with pegylated interferon (with
or without lamivudine) had HBV DNA levels <10,000 copies/mL, compared
to 15% of patients treated with lamivudine monotherapy (P = 0.039). |  | Similarly,
more patients treated with pegylated interferon had normal alanine aminotransferase
(ALT) at the end of follow-up compared to those treated with lamivudine monotherapy
(31% vs 18%; P = 0.032). |  | Use
of pegylated interferon and high baseline ALT were independent predictors of long-term
virological response (P = 0.040 and 0.01, respectively). |  | Among
participants treated with pegylated interferon (again, with or without lamivudine),
8.7% overall -- or 44% of those with undetectable HBV at the end of follow-up
-- cleared hepatitis B surface antigen (HBsAg), versus none treated with lamivudine
monotherapy. |
Based
on these findings, the study authors concluded, "Biochemical and virologic
responses were sustained for <3 years in approximately 25% of patients
given a 48-week course of peginterferon alpha-2a, with or without lamivudine." In
their discussion, they added, "The ability to induce HBsAg clearance -- an
outcome that is associated with long-term complication-free survival -- supports
the use of peginterferon alfa-2a as a first-line treatment of HBeAg negative disease,
avoiding the need for long-term therapy and the associated risks of developing
drug resistance in those patients who achieve and maintain their response." Drug
resistance is a known risk with lamivudine and other nucleoside/nucleotide analogs
that directly target HBV. Interferon is less likely to be limited by resistance
since it promotes immune response against HBV rather than interfering directly
with the viral life-cycle. Service
d'Hépatologie, Hôpital Beaujon, University of Paris, Clichy, France;
Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Policlinico di
Milano, Italy; Queen Mary Hospital, University of Hong Kong, Hong Kong, China;
Universita di Cagliari, Cagliari, Italy; University of Ankara, Faculty of Medicine,
Ankara, Turkey; NKC Institute of Gastroenterology and Hepatology, Department of
Internal Medicine, Songklanagarind Hospital, Prince of Songkla University, Hat
Yai, Thailand; Digestive Department, Beijing You-An Hospital, Beijing, China;
Department of Gastroenterology, Uludag University, Bursa, Turkey; Department of
Infectious Diseases, Ruijin Hospital, Shanghai, China; Department of Medicine
and Hepatology, Henry Dunant Hospital, Athens, Greece; Roche, Dee Why, Australia;
F. Hoffman-La Roche, Basel, Switzerland. 8/18/09 Reference P
Marcellin, F Bonino, GK Lau and others (for the Peginterferon alfa-2a in HBeAg-negative
Chronic Hepatitis B Study Group). Sustained response of hepatitis B e antigen-negative
patients 3 years after treatment with peginterferon alpha-2a. Gastroenterology
136(7): 2169-2179. June 2009. (Abstract).
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