Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.
Clin Gastroenterol Hepatol. 2013 Aug;11(8):1004-10.e1. doi: 10.1016/j.cgh.2013.01.026. Epub 2013 Feb 1.
BACKGROUND & AIMS: Few studies have investigated the effects of different nucleos(t)ide analogues against hepatitis B virus (HBV) on levels of covalently closed circular DNA (cccDNA) and hepatitis B surface antigen (HBsAg) in patients. We measured the magnitude of reduction of cccDNA and HBsAg by nucleos(t)ide analogue therapy and assessed the correlation between their reductions.
We recruited 124 patients who were treated with 1 of the 5 nucleos(t)ide analogues (lamivudine, adefovir, entecavir, telbivudine, or clevudine). All patients had undergone liver biopsy when treatment began (baseline) and 1 year later. The cccDNA and HBsAg levels were measured by real-time polymerase chain reaction and the Elecsys II HBsAg Assay, respectively.
After 1 year of treatment, HBV in 7 patients had become resistant to the nucleos(t)ide analogue. The remaining 117 patients had an average reduction of approximately 0.2 log10 IU/mL in HBsAg, 5 log10 IU/mL in serum level of HBV DNA, 2 log10 copies/cell in intrahepatic total HBV DNA, and 1 log10 copies/cell in cccDNA. Although 88 of 117 patients (75%) had undetectable serum levels of HBV DNA (<12 IU/mL), all had detectable levels of HBsAg, and only 5 (4%) had undetectable levels of cccDNA. On treatment with nucleos(t)ide analogues, patients with greater reductions in levels of cccDNA had greater reductions in HBsAg, but these reductions did not reach statistically significant correlations.
Although nucleos(t)ide analogues potently reduced serum levels of HBV DNA, the reduction of HBsAg and cccDNA was small. In short-term therapy, the magnitude of HBsAg reduction does not correlate with that of cccDNA reduction.
鲜有研究调查不同的核苷（酸）类似物抗乙型肝炎病毒（HBV）对患者cccDNA 和乙型肝炎表面抗原（HBsAg）水平的影响。我们测定了核苷（酸）类似物治疗后 cccDNA 和 HBsAg 降低的幅度，并评估了它们之间的相关性。
我们招募了 124 例接受 5 种核苷（酸）类似物（拉米夫定、阿德福韦酯、恩替卡韦、替比夫定或克拉夫定）之一治疗的患者。所有患者在治疗开始时（基线）和 1 年后均接受了肝活检。cccDNA 和 HBsAg 水平分别通过实时聚合酶链反应和 Elecsys II HBsAg 检测法测定。
治疗 1 年后，有 7 例患者的 HBV 对核苷（酸）类似物耐药。其余 117 例患者 HBsAg 平均降低约 0.2 log10 IU/mL，HBV DNA 血清水平降低 5 log10 IU/mL，肝内总 HBV DNA 降低 2 log10 拷贝/细胞，cccDNA 降低 1 log10 拷贝/细胞。尽管 117 例患者中有 88 例（75%）的 HBV DNA 血清水平不可检测（<12 IU/mL），但所有患者均有可检测到的 HBsAg 水平，只有 5 例（4%）的患者 cccDNA 不可检测。接受核苷（酸）类似物治疗时，cccDNA 水平降低幅度较大的患者 HBsAg 降低幅度也较大，但这些降低幅度未达到统计学显著相关性。
尽管核苷（酸）类似物能强力降低 HBV DNA 的血清水平，但 HBsAg 和 cccDNA 的降低幅度较小。在短期治疗中，HBsAg 降低幅度与 cccDNA 降低幅度无相关性。
