恩替卡韦相关的病毒学应答慢性乙型肝炎，肝硬化患者具有

StephenW

  Gut 2013;62:760-765 doi:10.1136/gutjnl-2012-302024

    Hepatology

    Original article

Virological response to entecavir is associated with a better clinical outcome in chronic hepatitis B patients with cirrhosis

    Roeland Zoutendijk1,
    Jurrien GP 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]

    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.
                           

StephenW

目的
恩替卡韦（ETV）是一种强效抑制病毒的复制，在慢性乙肝长期治疗可能导致肝纤维化的回归。本研究的目的是调查ETV对疾病进展的影响。

在一个多中心队列研究设计，372 ETV治疗的患者进行了研究。临床事件被定义为发展的肝细胞癌（HCC），肝功能失代偿或死亡。病毒学应答（VR）被定义为HBV DNA <80 IU / ml的。

结果
患者被列为慢性乙型肝炎无肝硬化组（n = 274），代偿期肝硬化组（n = 89）和失代偿期肝硬化组（n = 9）。 VR的概率不影响肝脏疾病的严重程度（P = 0.62）。在平均随访20个月（IQR 11-32）肝硬化患者（HR 15.41（95％CI 3.42〜69.54），P <0.001），临床事件的概率较高。 VR是与病情恶化的概率较低（HR 0.29（95％CI 0.08〜1.00），P = 0.05），维持既定的风险因素，如年龄校正后。 VR显着的好处肝硬化患者（HR 0.22（95％CI 0.05〜0.99），P = 0.04）和后仍然不包括失代偿期患者（HR为0.15（95％CI 0.03〜0.81），P = 0.03）。 2000年较高的HBV DNA阈值是不相关的疾病进展的可能性（HR 0.20（95％CI 0.03〜1.10），P = 0.10）IU / ml的。

结论
VR ETV与肝硬化患者病情恶化的概率较低，甚至可能的基线混杂因素校正后。当使用2000 IU / ml时，减少病毒的复制和疾病进展之间的关联，完整的病毒抑制是必不可少的核苷/核苷酸类似物治疗，尤其是肝硬化患者的阈值。

咬牙硬挺

翻译不好