核苷酸类似物停用后慢性乙型肝炎常见的实验室异常

StephenW

April 9, 2019
Laboratory Abnormalities Common in Chronic Hepatitis B After Nucleotide Analog Discontinuation
Hannah Dellabella


A significant number of patients with hepatitis B virus (HBV) infection who discontinue nucleotide analog use after an extended treatment period experience a grade 3 or higher laboratory abnormality, according to results published in The Lancet Gastroenterology & Hepatology. The results also indicated that some people Who are negative for hepatitis B e antigen (HBeAg) can achieve a low-replicative state.

This study included data on participants from 2 completed randomized controlled studies: GS-US-174-0102 (ClinicalTrials.gov identifier: NCT00117676) and GS-US-174-0103 (ClinicalTrials.gov identifier: NCT00116805). In both studies, participants Who had completed ≥8 years of nucleotide analog treatment, were positive for hepatitis B surface antigen (HBsAg) with HBV DNA concentration of <29 IU/mL, and were unwilling/unable to continue treatment were required to participate in a 24-week treatment -free follow-up (TFFU) phase.

This study includes data on participants in the TFFU phase. Participants were assessed at baseline and every 4 weeks for changes in qualitative serum HBsAg, HBV DNA, and alanine aminotransferase (ALT) concentrations.

A total of 124 participants started the TFFU phase, but 44% (n=54) did not complete 24 weeks of follow-up.

During the TFFU phase, 26% (n=32) of participants reported an adverse event (AE), with 4% (n=5) reporting serious AEs. The serious AEs included elevated ALT concentrations in 2 participants, hepatic flare in 2 participants , and increased lipase level in 1 participant.

The researchers found that 31% (n=38) of participants had grade 3 or higher laboratory abnormalities, most of which were ALT elevations (n=36).

Of 106 participants who were negative for HBeAg in the TFFU phase, 59% (n=63) completed 24 weeks of follow-up. The researchers observed HBsAg loss in 5% (n=5) of the HBeAg participants. In addition, 35 % (n=37) had both HBV DNA concentrations of <2000 IU/mL and ALT concentrations less than the upper limit of normal at week 24.

Of 18 participants who were positive for HBeAg who entered the TFFU phase, 7 (n=39%) completed 24 weeks of follow-up. Of these, none had HBsAg loss or HBV DNA <2000 IU/mL; 1 participant had an ALT Less than the upper limit of normal at week 24.
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"More data are required to predict which patients might benefit from [nucleotide analog withdrawal], and alternative cure strategies might might have needed before finite therapeutic options become a reality for more patients with chronic hepatitis B," wrote the researchers.

Disclosures: This study was sponsored by Gilead Sciences, Inc. The sponsor collected the data, monitored the study conduct, and performed the statistical analyses. Multiple authors declared affiliations with pharmaceutical companies. Please see the original reference for a full list of authors' disclosures .

Reference

Buti M, Wong DK, Gane E, et al. Safety and efficacy of stopping tenofovir disoproxil fumarate in patients with chronic hepatitis B following at least 8 years of therapy: a prespecified follow-up analysis of two randomised trials. Lancet Gastroenterol Hepatol. 2019 ;4(4): 296-304.

StephenW

2019年4月9日
核苷酸类似物停用后慢性乙型肝炎常见的实验室异常
汉娜德拉贝拉


根据发表在“柳叶刀胃肠病学与肝脏病学”上的研究结果，大量乙型肝炎病毒（HBV）感染患者在延长治疗期后停止使用核苷酸类似物会出现3级或更高级别的实验室异常。结果还表明，一些乙型肝炎e抗原阴性的人（HBeAg）可以达到低复制状态。

该研究包括来自2个完成的随机对照研究的参与者的数据：GS-US-174-0102（ClinicalTrials.gov标识符：NCT00117676）和GS-US-174-0103（ClinicalTrials.gov标识符：NCT00116805）。在这两项研究中，完成≥8年核苷酸类似物治疗的参与者，HBV DNA浓度<29 IU / mL的乙型肝炎表面抗原（HBsAg）呈阳性，并且不愿意/无法继续治疗需要参与为期24周的免费随访（TFFU）阶段。

该研究包括TFFU阶段参与者的数据。参与者在基线和每4周评估定性血清HBsAg，HBV DNA和丙氨酸氨基转移酶（ALT）浓度的变化。

共有124名参与者开始了TFFU阶段，但44％（n = 54）没有完成24周的随访。

在TFFU阶段，26％（n = 32）的参与者报告了不良事件（AE），4％（n = 5）报告了严重的AE。严重的AE包括2名参与者的ALT浓度升高，2名参与者的肝脏突然增加，以及1名参与者的脂肪酶水平增加。

研究人员发现，31％（n = 38）的参与者有3级或更高的实验室异常，其中大多数是ALT升高（n = 36）。

在TFFU阶段HBeAg阴性的106名参与者中，59％（n = 63）完成了24周的随访。研究人员观察到5％（n = 5）HBeAg参与者的HBsAg消失。此外，35％（n = 37）的HBV DNA浓度<2000 IU / mL，ALT浓度低于第24周的正常上限。

在进入TFFU阶段的HBeAg阳性的18名参与者中，7名（n = 39％）完成了24周的随访。其中，HBsAg缺失或HBV DNA <2000 IU / mL; 1名参与者的ALT低于第24周的正常上限。
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研究人员写道：“需要更多数据来预测哪些患者可能从[核苷酸类似物戒断]中受益，并且在有限治疗选择成为更多慢性乙型肝炎患者的现实之前，可能需要其他治疗策略。”

披露：本研究由Gilead Sciences，Inc。赞助。赞助商收集数据，监测研究行为，并进行统计分析。多位作者宣布与制药公司有关联。有关作者披露的完整列表，请参阅原始参考。

参考

Buti M，Wong DK，Gane E，et al。在治疗至少8年后停用替诺福韦地索普西富马酸盐治疗慢性乙型肝炎的安全性和有效性：两项随机试验的预先指定的随访分析。柳叶刀Gastroenterol Hepatol。 2019; 4（4）：296-304。