本帖最后由 StephenW 于 2012-4-26 12:30 编辑
Gut doi:10.1136/gutjnl-2012-302024
Virological response to entecavir is associated with a better clinical outcome in chronic hepatitis B patients with cirrhosis - Roeland Zoutendijk1,
- Jurrien G P Reijnders1,
- Fabien Zoulim2,
- Ashley Brown3,
- David J Mutimer4,
- Katja Deterding5,
- Wolf Peter Hofmann6,
- Joerg Petersen7,
- Massimo Fasano8,
- Maria Buti9,
- Thomas Berg10,
- Bettina E Hansen1,
- Milan J Sonneveld1,
- Heiner Wedemeyer5,
- Harry L A Janssen1,
- for the VIRGIL Surveillance Study Group
+ Author Affiliations - 1Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
- 2Department of Hepatology, Hospices Civils de Lyon; INSERM, U1052, Lyon University, Lyon, France
- 3Department of Hepatology and Gastroenterology, Imperial College London, London, UK
- 4NIHR Biomedical Research Unit and Centre for Liver Research, Queen Elizabeth Hospital, Birmingham, UK
- 5Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany
- 6Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany
- 7Ifi Institute, Asklepios Klinik St Georg, Hamburg, Germany
- 8Clinic of Infectious Diseases, University of Bari, Bari, Italy
- 9Department of Hepatology, Hospital Vall de Hebron and Ciberehd los Instituto Carlos III, Barcelona, Spain
- 10Department of Hepatology, University Clinic Leipzig, Leipzig, Germany
- Correspondence to Professor Dr Harry L A Janssen, Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwal 230, Room Ha 204, 3015 CE Rotterdam, The Netherlands; [email protected]
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Contributors RZ: acquisition of data, analysis and interpretation of data, drafting and finalising the article. JR: acquisition of data, drafting and finalising the article. FZ, AB, DJM, KD, JP, WPH, MB, MF, TB, HW: acquisition of data, critical revision of draft of article and approval of final version. MJS: interpretation of data, drafting of the article and approval of final version. BEH: analysis and interpretation of data, critical revision of draft of article and approval of final version. HLAJ: study concept and design, study supervision, analysis and interpretation of data, drafting and finalising the article.
- Revised 15 February 2012
- Accepted 28 February 2012
- Published Online First 5 April 2012
Abstract Objective Entecavir (ETV) is a potent inhibitor of viral replication in chronic hepatitis B and prolonged treatment may result in regression of fibrosis. The aim of this study was to investigate the effect of ETV on disease progression.
Design In a multicentre cohort study, 372 ETV-treated patients were investigated. Clinical events were defined as development of hepatocellular carcinoma (HCC), hepatic decompensation or death. Virological response (VR) was defined as HBV DNA <80 IU/ml.
Results Patients were classified as having chronic hepatitis B without cirrhosis (n=274), compensated cirrhosis (n=89) and decompensated cirrhosis (n=9). The probability of VR was not influenced by severity of liver disease (p=0.62). During a median follow-up of 20 months (IQR 11–32), the probability of developing clinical events was higher for patients with cirrhosis (HR 15.41 (95% CI 3.42 to 69.54), p<0.001). VR was associated with a lower probability of disease progression (HR 0.29 (95% CI 0.08 to 1.00), p=0.05) which remained after correction for established risk factors such as age. The benefit of VR was only significant in patients with cirrhosis (HR 0.22 (95% CI 0.05 to 0.99), p=0.04) and remained after excluding decompensated patients (HR 0.15 (95% CI 0.03 to 0.81), p=0.03). A higher HBV DNA threshold of 2000 IU/ml was not associated with the probability of disease progression (HR 0.20 (95% CI 0.03 to 1.10), p=0.10).
Conclusion VR to ETV is associated with a lower probability of disease progression in patients with cirrhosis, even after correction for possible baseline confounders. When using a threshold of 2000 IU/ml, the association between viral replication and disease progression was reduced, suggesting that complete viral suppression is essential for nucleoside/nucleotide analogue treatment, especially in patients with cirrhosis.
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发表于 2012-4-26 12:27