标题: Virological response to entecavir is associated with a lower probability of dise [打印本页] 作者: StephenW 时间: 2011-12-25 06:44 标题: Virological response to entecavir is associated with a lower probability of dise
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AASLD Liver Meeting. Abstract 240. Virological response to entecavir is
associated with a lower probability of disease progression: results from
377 chronic hepatitis B patients R. Zoutendijk1; J. G. Reijnders1; F.
Zoulim2; . S. Brown3; D. J. Mutimer4; K. Deterding5; W. P. Hofmann6; J.
Petersen7; M. Fasano8; M. Buti9; T. Berg10; M. J. Sonneveld1; B. E.
Hansen1; H. Wedemeyer 5; H. L. Janssen1 1. Department of Gastroenterology
and Hepatology, Erasmus MC, Rotterdam, Netherlands. 2. Department of
Hepatology, Hospices Civils de Lyon, Lyon, France. 3. Department of
Hepatology and Gastroenterology, Imperial College , London, United Kingdom.
4. NIHR Biomedical Research Unit and Centre for Liver Research, Queen
Elizabeth Hospital, Birmingham, United Kingdom. 5. Department of
Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover,
Hannover, Germany. 6. Medizinische Klinik 1, Klinikum der Johan Wolfgang
Goethe-Universitat, Frankfurt am Main, Germany. 7. Liver Unit, IFI
institute, Asklepios Klinik St. Georg, Hamburg, Germany. 8. Clinic of
Infectious Diseases, University of Bari, Bari, Italy. 9. Department of
Hepatology, Hospital Vall de Hebron, Barcelona, Spain. 10. Department of
Hepatology, University Clinic Leipzig, Leipzig, Germany.
Background The ultimate goal of hepatitis B virus (HBV) treatment is to
reduce disease progression to (decompensated) cirrhosis, hepatocellular
carcinoma (HCC) and premature death. Entecavir (ETV) inhibits HBV
replication, but whether ETV induced viral suppression is associated with
an improved clinical outcome is not well known. The aim of this study was
to investigate the effect of ETV therapy on event-free survival in chronic
HBV patients. Methods: In this investigator-initiated project we studied
all HBV monoinfected patients treated with ETV monotherapy from 10 large
European referral centers within the Virgil Network. Virological response
(VR) was defined as serum HBV DNA <80 IU/mL. Clinical endpoints considered
were hepatic decompensation, occurrence of HCC and death. Probability of
event-free survival was estimated by Kaplan Meier and Cox analysis. Results
A total of 377 patients (mean age 43±14 years; 75% male; 41% HBeAg+; HBV
DNA 5.7±2.1 log IU/ml, 30% nucleos(t)ide analogue (NA) and 22%
(peg)interferon experienced) treated with ETV monotherapy were included. A
total of 133 patients had advanced liver disease (by ultrasound or
histology) of whom 30 (23%) patients had advanced fibrosis (F3), 93 (70%)
patients had compensated cirrhosis and 10 (8%) patients had decompensated
cirrhosis at baseline. Cumulative probability of achieving VR was
comparable between these groups (p=0.49). Six patients developed
decompensation, four were diagnosed with HCC and eight patients died during
a median follow up of 19 [IQR 11-32] months. Median time to event was 36
(IQR 22-85) weeks. Patients with an event were older (p=0.08) and had a
higher MELD score at baseline (p=0.02). Occurrence of events was not
influenced by sex (p=0.37), HBeAg status (p=0.32), previous NA-therapy
(p=0.16), baseline ALT (p=0.95), HBV DNA (p=0.46) and follow up duration
(p=0.31). Cumulative probability of an event was higher in cirrhotic
patients, also when excluding decompensated patients (both p<0.001).
Importantly, patients with a VR during ETV therapy had a higher probability
of disease-free survival in a Cox model (HR 0.20, 95% CI 0.06-0.67,
p=0.009) with VR as time dependent covariate after adjusting for age, both
in the overall cohort and among patients with advanced liver disease (HR
0.18, 95% CI 0.05-0.73, p=0.02). When excluding events during the first
three months of ETV therapy this association remained significant.
Conclusion: This study shows that suppression of HBV by ETV improves the
probability of an event free survival in CHB. Importantly, the improved
clinical outcome is still apparent in patients with advanced liver disease.