Intradermal hepatitis B vaccination with or without Imiquimod in cirrhosis after prior vaccine nonresponse: A Randomised Trial.

IF 8.7 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

JHEP Reports Pub Date : 2026-09-21 DOI:10.1016/j.jhepr.2026.102039

Vincent Haghnejad, Mélissa Lucas, Nicolas Jacquinot, Hélène Jeulin, Sebastien Daude, Mouni Bensenane-Oussalah, Evelyne Schvoerer, Yohann Bernard, Amandine Luc, Jean-Pierre Bronowicki

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引用次数: 0

Abstract

Background and aims: Patients with cirrhosis show impaired immune responses to standard intramuscular (IM) hepatitis B virus (HBV) vaccination, resulting in low seroconversion rates. Intradermal (ID) vaccination and topical imiquimod have been proposed as strategies to enhance vaccine immunogenicity. We conducted a randomized controlled pilot trial to compare three HBV revaccination strategies in patients with advanced chronic liver disease (ACLD) who previously failed standard IM vaccination: IM revaccination, ID revaccination, and ID revaccination combined with imiquimod (ID+IMQ). The primary endpoint was seroconversion at Month 7, defined as anti-HBs titres ≥10 mIU/mL.

Methods: This monocentric, prospective study included 59 patients with ACLD and anti-HBs titres <10 mIU/mL after prior HBV vaccination. Patients were randomized (1:1:1) to receive either IM vaccination (n=19; Engerix-B® 20 μg IM at Months 0, 1 and 6), ID vaccination (n=19; two 10 μg ID injections at the same time points), or ID vaccination preceded by topical imiquimod 5% application (n=21).

Results: In the intention-to-treat analysis, seroprotection rates at month 7 were 36.8% in the IM group, 84.2% in the ID group, and 66.7% in the ID+IMQ group (p<0.01). After Bonferroni correction, only the ID versus IM comparison remained statistically significant (p=0.003). Geometric mean anti-HBs titres were significantly higher in the ID (116 mIU/mL) and ID+IMQ (107 mIU/mL) groups compared with the IM group (12 mIU/mL) (p=0.004). No severe vaccine-related adverse reactions were observed.

Conclusions: Intradermal HBV revaccination significantly improves seroconversion in non-responder patients with ACLD compared with IM vaccination, without additional benefit from imiquimod. These results support further evaluation of intradermal vaccination without imiquimod in a phase 3 trial.

Clinical trial number: The study protocol has been registered before the patients' recruitment, in the European Clinical Trials Database (EudraCT) of the European Medicine Agency (2021-000644-22), as well as on ClinicalTrials. gov (NCT05028322).

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先前疫苗无应答后肝硬化患者皮内接种有或没有咪喹莫特的乙肝疫苗：一项随机试验。

背景和目的：肝硬化患者对标准肌肉注射（IM）乙型肝炎病毒（HBV）疫苗的免疫应答受损，导致血清转换率低。皮内（ID）疫苗接种和外用咪喹莫特已被提出作为提高疫苗免疫原性的策略。我们进行了一项随机对照试验，比较了晚期慢性肝病（ACLD）患者先前未接种标准IM疫苗的三种HBV再接种策略：IM再接种、ID再接种和ID再接种联合咪喹莫特（ID+IMQ）。主要终点是第7个月的血清转化，定义为抗hbs滴度≥10 mIU/mL。结果：在意向治疗分析中，IM组第7个月的血清保护率为36.8%，ID组为84.2%，ID+IMQ组为66.7%(结论：与IM疫苗接种相比，皮内HBV再接种可显著改善无应答的ACLD患者的血清转化，咪喹莫特没有额外的益处。这些结果支持在3期试验中进一步评估不含咪喹莫特的皮内疫苗接种。临床试验编号：该研究方案在患者招募前已在欧洲药品管理局的欧洲临床试验数据库（EudraCT）（2021-000644-22）以及ClinicalTrials上注册。政府(NCT05028322)。

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来源期刊

JHEP Reports GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

12.40

自引率

2.40%

发文量

161

审稿时长

36 days

期刊介绍： JHEP Reports is an open access journal that is affiliated with the European Association for the Study of the Liver (EASL). It serves as a companion journal to the highly respected Journal of Hepatology. The primary objective of JHEP Reports is to publish original papers and reviews that contribute to the advancement of knowledge in the field of liver diseases. The journal covers a wide range of topics, including basic, translational, and clinical research. It also focuses on global issues in hepatology, with particular emphasis on areas such as clinical trials, novel diagnostics, precision medicine and therapeutics, cancer research, cellular and molecular studies, artificial intelligence, microbiome research, epidemiology, and cutting-edge technologies. In summary, JHEP Reports is dedicated to promoting scientific discoveries and innovations in liver diseases through the publication of high-quality research papers and reviews covering various aspects of hepatology.