质子泵抑制剂（PPI）常用于预防和治疗上消化道溃疡和出血。研究发现PPI治疗的肝硬化患者出现自发性细菌性腹膜炎和肝性脑病（HE）的发病率升高。然而，结果存在冲突，并且由于PPI被用于静脉曲张出血，这是感染和HE的主要风险因素之一，因此很难确定这些关联是否具有因果关系。在ATTIRE试验的后评价中，我们汇集了全部患者数据以研究PPI使用对临床结果的影响。ATTIRE是一项多中心、开放标签、随机试验，涉及777名住院急性并发症和白蛋白<30 g/L的失代偿性肝硬化成人，比较有针对性的20％人血清白蛋白（HAS）每日输注和标准治疗。研究招募时间为2016年1月25日至2019年6月28日，在英格兰、苏格兰和威尔士的35家医院进行。重要的排除标准包括寿命<8周的晚期肝细胞癌和接受姑息治疗的患者。在ATTIRE中，患者按试验入组时的PPI使用分组。我们研究了基线感染和HE以及医院获得性感染、新发HE、肾功能障碍和死亡的发生率。我们尝试使用倾向性评分匹配来考虑疾病严重程度的差异。总体而言，基线处方PPI与感染、肾功能障碍或死亡的增加不相关，但与住院期间grade III/IV HE的发生率显著增加相关（P = 0.011）。这仅在接受静脉PPI治疗的患者中显著，并且这些患者的静脉曲张出血发生率比不接受PPI治疗的患者高出>10倍，28天死亡率增加了近两倍。然而，由于在选择使用PPI的患者中存在如此强烈的选择，我们无法找到足够的非PPI患者进行匹配，所以倾向性评分匹配无法进行。我们发现，PPI使用对细菌移位、感染或全身性炎症标志物的血浆标记没有影响。我们完成的一项随机试验的实际数据显示，PPI在英国被广泛使用，对于住院治疗失代偿性肝硬化的患者来说，审慎使用是安全的。然而，开处方给PPI和不开处方的患者具有根本不同的表型，这是一种因适应症的混杂，应在解释研究并对其使用进行建议时认真考虑。威康信托基金会和卫生和社会保健部。©2023年作者。

Proton pump inhibitors (PPIs) are commonly prescribed to prevent and treat upper gastrointestinal ulceration and bleeding. Studies have identified increased incidence of spontaneous bacterial peritonitis and hepatic encephalopathy (HE) in cirrhosis patients taking PPIs. However, results are conflicting, and as PPIs are prescribed for variceal bleeding, a major risk factor for infection and HE, it is challenging to discern whether these associations are causal.In this post-hoc analysis of the ATTIRE trial, we pooled all patient data to investigate the effects of PPI use on clinical outcomes. ATTIRE was a multicentre, open-label, randomised trial of targeted 20% human albumin solution (HAS) daily infusions versus standard care involving 777 adults with decompensated cirrhosis hospitalised with acute complications and albumin <30 g/L. Study recruitment was between Jan 25, 2016, and June 28, 2019, at 35 hospitals across England, Scotland, and Wales. Key exclusion criteria were advanced hepatocellular carcinoma with life expectancy <8 weeks and patients receiving palliative care. In ATTIRE, patients were grouped by PPI use at trial entry. We studied infection and HE at baseline and incidence of hospital acquired infection, new onset HE, renal dysfunction and mortality. We attempted with propensity score matching to account for differences in disease severity.Overall PPI use at baseline was not associated with increased incidence of infection, renal dysfunction or mortality, but was associated with significantly increased incidence of grade III/IV HE during hospital stay (P = 0.011). This was only significant for those taking intravenous PPIs and these patients had >10 times the incidence of variceal bleeding and near double the 28-day mortality compared to non-PPI patients. However, propensity score matching was not possible as there was such a strong selection of patients for PPI use, that we could not find sufficient non-PPI patients to match to. We found no impact of PPI use on plasma markers of bacterial translocation, infection or systemic inflammation.Our real-world data from a completed randomised trial show that PPIs are widely prescribed in the UK and judicious use appears safe in patients hospitalised with decompensated cirrhosis. However, patients prescribed PPIs had fundamentally different phenotypes to those not prescribed PPIs, a form of confounding by indication, which should be strongly considered when interpreting studies and making recommendations about their use.Wellcome Trust and Department of Health and Social Care.© 2023 The Author(s).