Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Hepatology. 2017 Aug;66(2):335-343. doi: 10.1002/hep.28916. Epub 2016 Dec 24.
The long-term clinical impact of low-level viremia (LLV; <2,000 IU/mL) is not well understood. As a result, it is unclear whether the development of LLV during entecavir monotherapy requires a change in therapy. A retrospective cohort of 875 treatment-naive chronic hepatitis B virus (HBV) monoinfected patients (mean age 47.7 years, male = 564 [65.5%], cirrhosis = 443 [50.6%]) who received entecavir monotherapy were analyzed for the development of hepatocellular carcinoma (HCC). The HCC risk was compared between patients who maintained virological response (MVR), defined by persistently undetectable HBV DNA (<12 IU/mL), and patients who experienced LLV, defined by either persistent or intermittent episodes of <2,000 IU/mL detectable HBV DNA. During a median 4.5 years of follow-up (range 1.0-8.7 years), HCC was diagnosed in 85 patients (9.7%). HCC developed more frequently in patients who experienced LLV than MVR (14.3% versus 7.5% at 5 years, P = 0.015). The hazard ratio comparing those with LLV to MVR was 1.98 (95% confidence interval = 1.28-3.06, P = 0.002, adjusted for age, sex, hepatitis B e antigen, baseline HBV DNA levels, and cirrhosis). Among patients with cirrhosis, those with LLV exhibited a significantly higher HCC risk than those with MVR (HCC incidence rate at 5 years 23.4% versus 10.3%, adjusted hazard ratio = 2.20, 95% confidence interval 1.34-3.60; P = 0.002). However, for patients without cirrhosis, there was no significant difference in the HCC risk between LLV and MVR.
LLV observed during entecavir monotherapy was associated with a higher risk of HCC, especially for those with cirrhosis, indicating that LLV during potent antiviral therapy is consequential. (Hepatology 2017;66:335-343).
低水平病毒血症（LLV；<2000IU/mL）的长期临床影响尚不清楚。因此，尚不清楚恩替卡韦单药治疗期间发生 LLV 是否需要改变治疗方案。对 875 例接受恩替卡韦单药治疗的初治慢性乙型肝炎病毒（HBV）单感染患者（平均年龄 47.7 岁，男性 564 例[65.5%]，肝硬化 443 例[50.6%]）进行了回顾性队列分析，以评估其发生肝细胞癌（HCC）的风险。将病毒学应答维持（MVR）患者（定义为持续检测不到 HBV DNA [<12IU/mL]）与发生 LLV 患者（定义为持续或间歇性<2000IU/mL 可检测 HBV DNA）的 HCC 风险进行比较。在中位 4.5 年（1.0-8.7 年）的随访期间，诊断出 85 例 HCC（9.7%）。与 MVR 相比，发生 LLV 的患者 HCC 发生率更高（5 年时分别为 14.3%和 7.5%，P=0.015）。与 MVR 相比，发生 LLV 的患者发生 HCC 的风险比为 1.98（95%可信区间为 1.28-3.06，P=0.002，校正年龄、性别、乙型肝炎 e 抗原、基线 HBV DNA 水平和肝硬化因素）。在肝硬化患者中，发生 LLV 的患者 HCC 风险显著高于 MVR 患者（5 年 HCC 发生率分别为 23.4%和 10.3%，校正风险比=2.20，95%可信区间为 1.34-3.60；P=0.002）。然而，对于无肝硬化的患者，LLV 与 MVR 之间 HCC 风险无显著差异。
恩替卡韦单药治疗期间观察到的 LLV 与 HCC 风险增加相关，尤其是对肝硬化患者而言，表明强效抗病毒治疗期间的 LLV 具有重要意义。（《肝脏病学》2017；66：335-343）
