Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea. Biomedical Research Center, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea. These authors share co-first authorship: Jung Woo Shin and Seok Won Jung.
Am J Gastroenterol. 2018 Jul;113(7):998-1008. doi: 10.1038/s41395-018-0093-9. Epub 2018 Jun 8.
Optimal adherence to nucleoside analogue treatment is necessary to achieve undetectable levels of hepatitis B virus (HBV) DNA in patients with chronic hepatitis B (CHB), and to prevent cirrhotic complications. However, any large long-term follow-up study has not been investigated the effect of adherence to entecavir (ETV) treatment on specific liver-related events (LREs), namely, hepatocellular carcinoma (HCC), cirrhotic complications, and mortality.
This was a 10-year longitudinal observational study of treatment-naïve patients with CHB who received ETV treatment. The primary outcome was the cumulative probability of LREs. The cumulative level of adherence to medication was categorized as good (≥90%) or poor (<90%).
Data from 894 treatment-naïve CHB patients who received ETV were analyzed. Overall mean adherence rates were 89.1%. Patients with poor adherence had a higher risk of virologic breakthrough (VBT) (HR, 22.42; 95% CI, 19.57-52.52; P < 0.001) than those with good adherence. Multivariate analyses showed a higher risk of liver-related (HR, 14.29; 95% CI, 3.49-58.47; P < 0.001) or all-cause (HR, 4.96; 95% CI, 2.19-11.27; P < 0.001) mortality, HCC (HR, 2.86; 95% CI, 1.76-4.64; P < 0.001), and cirrhotic complications (HR, 2.86; 95% CI, 1.93-4.25; P < 0.001) with poor adherence. Medication adherence was further stratified into three groups according to adherence rates of <70%, ≥70 to <90%, and ≥90%. The dose-response analyses of adherence rates showed that the risk of LREs increased progressively as medication adherence declined. In particular, the unfavorable effects of nonadherence were more pronounced in patients with cirrhosis.
Poor adherence to medication was associated with a higher mortality and greater risk of HCC and cirrhotic complications, particularly among patients with liver cirrhosis.
核苷类似物治疗的最佳依从性对于慢性乙型肝炎（CHB）患者达到乙型肝炎病毒（HBV）DNA 不可检测水平以及预防肝硬化并发症是必要的。然而，任何大型长期随访研究都没有调查药物依从性对特定肝脏相关事件（LREs）的影响，即肝细胞癌（HCC）、肝硬化并发症和死亡率。
这是一项对接受恩替卡韦（ETV）治疗的初治 CHB 患者进行的 10 年纵向观察性研究。主要结局是 LREs 的累积概率。药物依从性的累积水平分为良好（≥90%）或不良（<90%）。
分析了 894 名接受 ETV 治疗的初治 CHB 患者的数据。总体平均依从率为 89.1%。依从性差的患者发生病毒学突破（VBT）的风险更高（HR，22.42；95%CI，19.57-52.52；P<0.001）。多变量分析显示，药物依从性差与肝脏相关（HR，14.29；95%CI，3.49-58.47；P<0.001）或全因（HR，4.96；95%CI，2.19-11.27；P<0.001）死亡率、HCC（HR，2.86；95%CI，1.76-4.64；P<0.001）和肝硬化并发症（HR，2.86；95%CI，1.93-4.25；P<0.001）的风险更高。药物依从性进一步根据依从率<70%、70%至<90%和≥90%分为三组。药物依从率的剂量反应分析表明，随着药物依从性的下降，LREs 的风险逐渐增加。特别是在肝硬化患者中，不依从的不利影响更为明显。
药物依从性差与死亡率升高以及 HCC 和肝硬化并发症风险增加相关，尤其是在肝硬化患者中。
