Antiviral effect of entecavir in chronic hepatitis B: Influence of prior exposure to nucleos(t)ide analogues

Reijnders, Jurriën G.P.; Deterding, Katja; Petersen, Jörg; Zoulim, Fabien; Santantonio, Teresa; Buti, Maria; van Bömmel, Florian; Hansen, Bettina E.; Wedemeyer, Heiner; Janssen, Harry L.A.; for the VIRGIL Surveillance Study Group,

doi:10.1016/j.jhep.2010.01.012

« Previous Next »Journal of Hepatology
Volume 52, Issue 4 , Pages 493-500, April 2010

Antiviral effect of entecavir in chronic hepatitis B: Influence of prior exposure to nucleos(t)ide analogues

Jurriën G.P. Reijnders
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Gravendijkwal 230, Room Ha 204, 3015 CE Rotterdam, The Netherlands
Katja Deterding
- Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany
Jörg Petersen
- Department of Medicine, University of Hamburg, Hamburg, Germany
Fabien Zoulim
- Department of Hepatology, Hotel Dieu Hospital Lyon, Lyon, France
Teresa Santantonio
- Clinic of Infectious Diseases, University of Foggia, Foggia, Italy
Maria Buti
- Department of Hepatology, Hospital Vall de Hebron, and Ciber-EHD, Barcelona, Spain
Florian van Bömmel
- Department of Gastroenterology and Hepatology, Charité University Medical Center Berlin, Berlin, Germany
Bettina E. Hansen
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Gravendijkwal 230, Room Ha 204, 3015 CE Rotterdam, The Netherlands
Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany
Harry L.A. Janssen
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Gravendijkwal 230, Room Ha 204, 3015 CE Rotterdam, The Netherlands
- Corresponding author. Tel.: +31 (0) 10 703 5942; fax: +31 (0) 10 436 5916.
for the VIRGIL Surveillance Study Group

Received 8 June 2009; received in revised form 31 August 2009; accepted 5 October 2009. published online 03 February 2010.

Background & Aims

Entecavir is a potent inhibitor of viral replication in nucleos(t)ide analogue (NA)-naïve chronic hepatitis B patients, but data on the efficacy in NA-experienced subjects are limited.

Methods

In a multi-center cohort study we investigated 161 chronic hepatitis B patients (34% NA-experienced) treated with entecavir monotherapy.

Results

During a median follow-up of 11 (3–23)months, 82 (79%) of 104 NA-naïve patients achieved virologic response (VR), defined as HBV DNA <80IU/ml, and none of the patients (0%) developed genotypic entecavir-resistance. VR was demonstrated in 31 (54%) of 57 NA-experienced patients during a median follow-up of 12 (3–31)months. Patients with lamivudine-resistant mutations at the start of entecavir monotherapy had a reduced probability of achieving VR compared to lamivudine-naïve patients (HR 0.14; 95% CI 0.04–0.58; p=0.007). Antiviral efficacy was not decreased by prior treatment with lamivudine when lamivudine-resistance had never developed (HR 0.81; 95% CI 0.43–1.52; p=0.52). Prior adefovir therapy without development of adefovir-resistance (HR 0.84; 95% CI 0.43–1.64; p=0.61) and presence of adefovir-resistance (HR 0.86; 95% CI 0.27–2.71; p=0.80) did not influence antiviral response to entecavir. Switching to a tenofovir-containing treatment regimen resulted in viral load decline in patients with entecavir-resistance associated mutations.

Conclusions

Entecavir proved to be efficacious in NA-naïve patients. The antiviral efficacy of entecavir was not influenced by prior treatment with adefovir or presence of adefovir-resistance. Entecavir should not be used in patients with previous lamivudine-resistance, yet it may still be an option in lamivudine-experienced patients in case lamivudine-resistance never developed.

Keywords: Entecavir, Hepatitis B, Lamivudine, Adefovir, Antiviral therapy

Abbreviations: NA, nucleos(t)ide analogues, HBV, hepatitis B virus, ETV, entecavir, LAM, lamivudine, HBeAg, hepatitis B e antigen, VR, virologic response, HIV, human immunodeficiency virus, HCV, hepatitis C virus, HDV, hepatitis delta virus, ALT, alanine aminotransferase, HBsAg, hepatitis B surface antigen, anti-HBs, antibody against HBsAg, anti-HBe, antibody against HBeAg, BMI, body mass index, ADV, adefovir dipivoxil, ULN, upper limit of normal, TDF, tenofovir disoproxil fumarate, HR, hazard ratio, CI, confidence interval