恩替卡韦治疗肾功能不全患者的乙肝病毒

StephenW

Entecavir for Treatment of HBV in Patients With Renal Dysfunction
Gary Rothbard, MD, MS
In patients infected with hepatitis B virus (HBV) who had severe renal impairment, entecavir was found to be safe and effective for the treatment of HBV infection and did not have a negative impact on kidney function, according to a report published in Hepatology Research.

The nucleoside analogs tenofovir-disoproxil-fumarate, tenofovir-alafenamide, and entecavir are among the currently recommended first-line HBV therapies available to clinicians. However, the first medication carries known risks for nephrotoxicity, while the second is relatively new and unproven in patients with chronic kidney disease (CKD). This leaves entecavir as a potentially more suitable treatment for individuals infected with HBV who have serious renal dysfunction. Investigators sought to clarify the safety and efficacy of entecavir in this population, given the sparse data and limited evidence offered in the literature.
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Between 2006 and 2018, a multicenter retrospective study enrolled 273 patients (median age, 57 years; 53.1% male) >20 years of age who had been treated with entecavir monotherapy (0.5 mg orally, given daily to weekly, depending on renal disease severity) for HBV infection for >1 year. Participants were evaluated at baseline and annually following initiation of therapy.

Primary outcomes included entecavir efficacy — assessed by viral load reduction rates, alanine transaminase normalization and virologic breakthrough rates — as well as renal function changes, according to baseline renal function. Participants were categorized by level of baseline renal dysfunction, with significant differences in baseline demographic and clinical characteristics existing between those with CKD stage G1/G2 and those with CKD stage G3/G4/G5 or who were on hemodialysis. Among all enrolled patients, at baseline there were 25 (9.2%), 5 (1.8%), and 10 (3.7%) people with CKD stage G3, stage G4/G5, and on hemodialysis, respectively. In the remainder of participants, kidney disease was categorized as stage G1/G2, with normal renal function and estimated glomerular filtration rates (eGFR) >60 mL/min/1.73 m2.

At 1, 2, and 3 years following entecavir therapy initiation, 84.2%, 94.0%, and 96.2% of patients, respectively, demonstrated substantial viral load reduction and disappearance of HBV-DNA. In people undergoing hemodialysis, entecavir had 100% efficacy and no virologic breakthrough after 1 year. A total of 7 individuals (2.5%) demonstrated virologic responses during the study. There were similar rates of HBV-DNA disappearance, virologic breakthrough, and alanine transaminase normalization (89.7%) over time seen in those with and without renal impairment.

Regarding impact on renal function, at 5 years after entecavir initiation, participants without baseline renal dysfunction had significant worsening of eGFR over time (P <.001), while those with CKD stage G3/G4/G5 showed nonsignificant improvements and a trend toward restoration of eGFR (P =.184). Entecavir was found to be safe over the course of the study, with no patients undergoing hemodialysis reporting serious adverse events that caused discontinuation.

Study strengths included a long median observation period, analysis of renal impact according to baseline renal function, and inclusion of several patients undergoing hemodialysis. Study limitations included a retrospective design with missing data, inability to track all co-administered medications, significant differences in baseline characteristics between groups, and a potentially insufficient treatment follow-up duration.

“In conclusion, [entecavir] for HBV-infected patients with moderate to severe renal dysfunction, including hemodialysis patients, is highly effective. [Entecavir] is indicated to be safe for patients with renal dysfunction,” noted the authors. They recommended that future research include longer studies involving more patients.

Funding and Conflicts of Interest Disclosures:

This study was supported in part by grants from the Japan Agency for Medical Research and Development (AMED; grant number grant number 19fk0210022h0103, 19fk0210018h0003, 19fk0310101s0503, 19fk0210048s0501, 19fk0210058h0001, 19fk0210047s04010401) and SPS KAKENHI; (Grant Number 19K0845819K08458).

Professor Naoya Sakamoto received lecture fees from Bristol Myers Squibb and Pharmaceutical K.K, grants and endowments from MSD K.K and Chugai Pharmaceutical Co., Ltd, and a research grant from Gilead Sciences, Inc. Dr. Goki Suda received research grants from Bristol Myers Squibb, MSD K.K, and Gilead Sciences. The other authors have nothing to disclose.

Reference

Suzuki K, Suda G, Yamamoto Y, et al. Entecavir treatment of hepatitis B

StephenW

恩替卡韦治疗肾功能不全患者的乙肝病毒
马里兰州医学博士加里·罗斯巴德
根据《肝病研究》上发表的一份报告，在患有严重肾功能不全的乙型肝炎病毒（HBV）感染的患者中，发现恩替卡韦对于治疗HBV感染是安全有效的，并且对肾脏功能没有负面影响。

核苷类似物替诺福韦-二甲环磷酰胺-富马酸酯，替诺福韦-阿拉芬酰胺和恩替卡韦是目前推荐给临床医生使用的一线HBV治疗药物。但是，第一种药物具有已知的肾毒性风险，而第二种药物相对较新，并且在慢性肾脏病（CKD）患者中未经证实。恩替卡韦对于患有严重肾功能不全的HBV感染者而言，可能是更合适的治疗方法。鉴于文献中数据稀少且证据有限，研究人员试图阐明恩替卡韦在该人群中的安全性和有效性。
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在2006年至2018年之间，一项多中心回顾性研究纳入了273名年龄在20岁以上，接受恩替卡韦单药治疗（0.5 mg口服，每天至每周一次，取决于肾脏疾病严重程度）的患者（中位年龄为57岁；男性为53.1％），年龄> 20岁）对于HBV感染> 1年。开始治疗后，在基线和每年对参与者进行评估。

主要结果包括恩替卡韦疗效（根据病毒载量降低率，丙氨酸转氨酶正常化和病毒学突破率评估），以及根据基线肾功能的肾功能变化。参与者按基线肾功能不全的等级进行分类，在CKD G1 / G2期和CKD G3 / G4 / G5期或接受血液透析的人群之间，基线人口统计学和临床​​特征存在显着差异。在所有入组患者中，基线时分别有25名（9.2％），5名（1.8％）和10名（3.7％）CKD G3期，G4 / G5期和血液透析患者。在其余的参与者中，肾脏疾病被分类为G1 / G2期，肾功能正常，肾小球滤过率（eGFR）估计> 60 mL / min / 1.73 m2。

在恩替卡韦治疗开始后的第1、2和3年，分别有84.2％，94.0％和96.2％的患者表现出明显的病毒载量减少和HBV-DNA消失。在接受血液透析的患者中，恩替卡韦1年后疗效达100％，无病毒学突破。在研究期间，共有7个人（2.5％）表现出病毒学应答。在有和没有肾功能不全者中，随着时间的推移，HBV-DNA消失，病毒学突破和丙氨酸转氨酶正常化的发生率相似（89.7％）。

关于对肾功能的影响，在开始恩替卡韦治疗后的5年，没有基线肾功能不全的参与者的eGFR随着时间的推移而显着恶化（P <.001），而CKD期为G3 / G4 / G5的参与者表现出无明显改善，并且有恢复的趋势。 eGFR（P = .184）。恩替卡韦在整个研究过程中被发现是安全的，没有接受血液透析的患者报告了导致停药的严重不良事件。

研究优势包括较长的中位观察期，根据基线肾功能进行的肾脏影响分析以及包括几位接受血液透析的患者。研究的局限性包括缺少数据的回顾性设计，无法追踪所有共同给药的药物，各组之间基线特征的显着差异以及治疗随访时间可能不足。

“总的来说，[恩替卡韦]对于中度至重度肾功能不全的HBV感染患者，包括血液透析患者，是非常有效的。作者指出[恩替卡韦]对于肾功能不全的患者是安全的。他们建议将来的研究包括更长的研究，涉及更多的患者。

资金和利益冲突披露：

这项研究得到了日本医学研究与发展局（AMED;授予号为19fk0210022h0103、19fk0210018h0003、19fk0310101s0503、19fk0210048s0501、19fk0210058h0001、19fk0210047s04010401）和SPS KAKENHI的资助的部分支持。 （授权号19K0845819K08458）。

坂本直也教授获得了百时美施贵宝公司（Bristol Myers Squibb）和Pharmaceutical KK的演讲费，MSD KK和中外制药有限公司的赠款和捐赠，以及吉利德科学公司（Gilead Sciences，Inc.）的研究赠款。 MSD KK和Gilead Sciences。其他作者没有什么可披露的。

参考

Suzuki K，Suda G，Yamamoto Y等。恩替卡韦治疗乙型肝炎