Inoue Jun, Akahane Takehiro, Kobayashi Tomoo, Obara Noriyuki, Umetsu Teruyuki, Kakazu Eiji, Ninomiya Masashi, Iwata Tomoaki, Sano Akitoshi, Tsuruoka Mio, Sato Kosuke, Masamune Atsushi
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan.
Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Miyagi 986-8522, Japan.
Biomed Rep. 2021 Feb;14(2):20. doi: 10.3892/br.2020.1396. Epub 2020 Dec 1.
Although hepatitis B surface antigen (HBsAg) removal is considered the goal of chronic hepatitis B treatment, it can rarely be achieved with nucleos(t)ide analogues (NAs). It has been reported that tenofovir disoproxil fumarate (TDF) is superior in reducing HBsAg compared with entecavir (ETV) in treatment-naïve patients; however, the effect of TDF in patients who have received NAs is still unclear. The aim of the present study was to evaluate the efficacy of switching from ETV to TDF in patients who were already receiving ETV. A pilot randomized controlled study for 2 years in patients who had been treated with ETV for >1 year and did not exhibit drug resistance was performed (Clinical trial registration: UMIN000021948, UMIN-CTR, May 1, 2016). A total of 20 patients were enrolled and 19 patients were randomized into 2 groups, a TDF-switching group (n=12) or an ETV-continuing group (n=7). The mean change in HBsAg levels after 2 years was greater in the TDF group compared with the ETV group, but the difference was not significant (-0.25 vs. -0.06 log IU/ml). In the TDF group, hepatitis B e antigen (HBeAg)-positive patients at baseline showed significantly greater changes in HBsAg (-0.63 vs. -0.03 log IU/ml; P=0.030). In contrast, no difference between HBeAg-positive and HBeAg-negative patients was observed in the ETV group. No significant differences of estimated glomerular filtration rate and inorganic phosphorus changes were observed among the TDF and ETV groups. In conclusion, a significant HBsAg decrease was not achieved after switching from ETV to TDF in the overall analysis, but HBeAg-positive patients showed a larger HBsAg decrease after switching treatment.
虽然乙肝表面抗原（HBsAg）清除被视为慢性乙型肝炎治疗的目标，但使用核苷（酸）类似物（NAs）很少能实现这一目标。据报道，在初治患者中，替诺福韦酯（TDF）在降低HBsAg方面优于恩替卡韦（ETV）；然而，TDF在接受过NAs治疗的患者中的效果仍不明确。本研究的目的是评估已接受ETV治疗的患者从ETV换用TDF的疗效。对接受ETV治疗超过1年且未出现耐药的患者进行了一项为期2年的前瞻性随机对照研究（临床试验注册号：UMIN000021948，UMIN临床试验注册中心，2016年5月1日）。共纳入20例患者，其中19例患者被随机分为2组，即TDF换药组（n = 12）和ETV继续治疗组（n = 7）。2年后，TDF组的HBsAg水平平均变化大于ETV组，但差异无统计学意义（-0.25对-0.06 log IU/ml）。在TDF组中，基线时乙肝e抗原（HBeAg）阳性的患者HBsAg变化显著更大（-0.63对-0.03 log IU/ml；P = 0.030）。相比之下，ETV组中HBeAg阳性和HBeAg阴性患者之间未观察到差异。TDF组和ETV组之间估计肾小球滤过率和无机磷变化无显著差异。总之，在总体分析中，从ETV换用TDF后未实现HBsAg的显著下降，但HBeAg阳性患者在换药治疗后HBsAg下降幅度更大。
