Real-world hepatic safety of the potassium-competitive acid blocker: A RUCAM-adjudicated multicenter cohort study.

IF 16.2 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Clinical Gastroenterology and Hepatology Pub Date : 2026-10-09 DOI:10.1016/j.cgh.2026.09.045

Hye Yeon Chon, Hae-Ryong Yun, Da Hyun Jung, Jeonghyun Lim, So Hyeon Gwon, Nak-Hoon Son, Young Hoon Youn, Cheal Wung Huh

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引用次数: 0

Abstract

Background & aims: Early-generation potassium-competitive acid blockers (P-CABs) were withdrawn during clinical development because of hepatotoxicity, and long-term real-world hepatic safety data for newer P-CABs remain scarce. Drug-induced liver injury (DILI) ascertainment in observational studies is further limited by the reliance on nonspecific outcome definitions. We aimed to evaluate the hepatic safety of tegoprazan compared with proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) using Roussel Uclaf Causality Assessment Method (RUCAM)-based adjudication.

Methods: This large-scale, multicenter retrospective cohort study used a new-user, active-comparator design including users of tegoprazan, PPIs, or H2RAs with ≥30 cumulative defined daily doses (cDDDs). Propensity score matching (PSM) balanced demographics, comorbidities, hepatotoxic co-medications, and baseline liver biochemistry. The primary outcome was RUCAM-adjudicated DILI (score ≥3); hazard ratios (HRs) were estimated by Cox regression with Firth's penalized likelihood for rare events.

Results: Of 363,340 screened patients, 11,190 were included; PSM yielded 5,586 (1,862/group). RUCAM-possible DILI was very rare, with 3, 2, and 3 events (0.17, 0.07, and 0.15 per 100 person-years) in the tegoprazan, PPI, and H2RA groups, respectively. No increased risk was detected for tegoprazan versus H2RAs (Firth-penalized HR 0.98; 95% CI, 0.20-4.95) or PPIs (HR 1.63; 95% CI, 0.28-9.56), with wide confidence intervals. No case exceeded the "possible" RUCAM threshold.

Conclusions: No increased risk of RUCAM-possible DILI was detected for tegoprazan compared with PPIs or H2RAs, although the small number of events precludes a conclusion of equivalent safety. The rarity of RUCAM-possible events across all acid-suppressive drug classes raises the possibility that previously reported signals may partly reflect differences in outcome ascertainment.

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钾竞争酸阻滞剂的实际肝脏安全性：一项rucam裁定的多中心队列研究。

背景与目的：早期的钾竞争性酸阻滞剂（p - cab）由于肝毒性在临床开发过程中被停药，新的p - cab的长期真实肝脏安全性数据仍然缺乏。观察性研究中药物性肝损伤（DILI）的确定进一步受到非特异性结局定义的限制。我们的目的是通过基于Roussel - Uclaf因果关系评估方法（RUCAM）的判定来评估替戈拉嗪与质子泵抑制剂（PPIs）和组胺-2受体拮抗剂（H2RAs）的肝脏安全性。方法：这项大规模、多中心回顾性队列研究采用新用户、主动比较者设计，包括替格拉赞、PPIs或H2RAs的累计限定日剂量(cDDDs)≥30的使用者。倾向评分匹配（PSM）平衡了人口统计学、合并症、肝毒性联合用药和基线肝生化。主要终点为rucam判定的DILI（评分≥3）；风险比（hr）采用罕见事件的费斯惩罚似然的Cox回归估计。结果：在363340例筛查患者中，纳入11190例；PSM产5586个（1862个/组）。rucam -可能的DILI非常罕见，替戈拉赞组、PPI组和H2RA组分别有3、2和3个事件（0.17、0.07和0.15 / 100人年）。tegoprazan与H2RAs （firth惩罚风险比0.98;95% CI, 0.20-4.95）或PPIs（风险比1.63;95% CI, 0.28-9.56）相比，没有发现风险增加，置信区间很宽。没有病例超过“可能的”RUCAM阈值。结论：与ppi或H2RAs相比，替戈拉赞未检测到rucam -可能DILI的风险增加，尽管少量事件排除了同等安全性的结论。在所有抑酸药物类别中rucam可能事件的稀缺性提高了先前报道的信号可能部分反映结果确定差异的可能性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Gastroenterology and Hepatology 医学-胃肠肝病学

CiteScore

16.90

自引率

4.80%

发文量

903

审稿时长

22 days

期刊介绍： Clinical Gastroenterology and Hepatology (CGH) is dedicated to offering readers a comprehensive exploration of themes in clinical gastroenterology and hepatology. Encompassing diagnostic, endoscopic, interventional, and therapeutic advances, the journal covers areas such as cancer, inflammatory diseases, functional gastrointestinal disorders, nutrition, absorption, and secretion. As a peer-reviewed publication, CGH features original articles and scholarly reviews, ensuring immediate relevance to the practice of gastroenterology and hepatology. Beyond peer-reviewed content, the journal includes invited key reviews and articles on endoscopy/practice-based technology, health-care policy, and practice management. Multimedia elements, including images, video abstracts, and podcasts, enhance the reader's experience. CGH remains actively engaged with its audience through updates and commentary shared via platforms such as Facebook and Twitter.