Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Gut. 2013 May;62(5):760-5. doi: 10.1136/gutjnl-2012-302024. Epub 2012 Apr 5.
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.
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.
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).
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.
恩替卡韦（ETV）是慢性乙型肝炎病毒复制的有效抑制剂，长期治疗可能导致纤维化消退。本研究旨在探讨 ETV 对疾病进展的影响。
在一项多中心队列研究中，对 372 例 ETV 治疗患者进行了调查。临床事件定义为肝细胞癌（HCC）的发展、肝功能失代偿或死亡。病毒学应答（VR）定义为 HBV DNA<80IU/ml。
患者分为无肝硬化的慢性乙型肝炎（n=274）、代偿性肝硬化（n=89）和失代偿性肝硬化（n=9）。VR 的概率不受肝病严重程度的影响（p=0.62）。在中位随访 20 个月（IQR 11-32）期间，肝硬化患者发生临床事件的概率较高（HR 15.41（95%CI 3.42-69.54），p<0.001）。VR 与疾病进展的概率较低相关（HR 0.29（95%CI 0.08-1.00），p=0.05），在校正年龄等既定危险因素后仍保持不变。VR 的益处仅在肝硬化患者中具有统计学意义（HR 0.22（95%CI 0.05-0.99），p=0.04），并且在排除失代偿患者后仍然存在（HR 0.15（95%CI 0.03-0.81），p=0.03）。较高的 HBV DNA 阈值 2000IU/ml 与疾病进展的概率无关（HR 0.20（95%CI 0.03-1.10），p=0.10）。
即使在校正可能的基线混杂因素后，ETV 的 VR 与肝硬化患者疾病进展的概率降低相关。当使用 2000IU/ml 的阈值时，病毒复制与疾病进展之间的关联减弱，这表明完全抑制病毒对于核苷（酸）类似物治疗至关重要，尤其是在肝硬化患者中。
