PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Wellcome Trust and Department of Health and Social Care.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Wellcome Trust and Department of Health and Social Care.
摘要：
■质子泵抑制剂（PPI）通常用于预防和治疗上消化道溃疡和出血。研究发现，在服用PPI的肝硬化患者中，自发性细菌性腹膜炎和肝性脑病（HE）的发生率增加。然而,结果是相互矛盾的，由于PPI是用于静脉曲张破裂出血的处方，感染和HE的主要危险因素，辨别这些关联是否是因果关系具有挑战性。
■在对ATTIRE试验的事后分析中，我们汇集了所有患者数据,以研究PPI使用对临床结局的影响.ATTIRE是一个多中心,开放标签，针对20％人白蛋白溶液（HAS）每日输注与标准治疗的随机试验，涉及777例失代偿性肝硬化成人，因急性并发症和白蛋白<30g/L住院研究招募时间为2016年1月25日至2019年6月28日，在英格兰35家医院进行，苏格兰,威尔士。关键排除标准是预期寿命<8周的晚期肝细胞癌和接受姑息治疗的患者。在ATTIRE,患者在进入试验时按PPI使用情况分组.我们研究了基线时的感染和HE以及医院获得性感染的发生率，新发作的他，肾功能不全和死亡率。我们尝试用倾向评分匹配来解释疾病严重程度的差异。
■基线时使用总PPI与感染发生率增加无关，肾功能障碍或死亡率，但与住院期间III/IV级HE发生率显著增加相关(P=0.011).这仅对那些服用静脉PPI的患者有意义，与非PPI患者相比，这些患者静脉曲张破裂出血的发生率>10倍，28天死亡率接近两倍。然而,倾向评分匹配是不可能的，因为PPI使用的患者选择如此强烈，我们找不到足够的非PPI患者来匹配。我们发现使用PPI对细菌易位的血浆标志物没有影响，感染或全身性炎症。
■我们从完成的随机试验中获得的实际数据表明，PPI在英国被广泛开处方，合理使用对失代偿期肝硬化住院患者似乎是安全的。然而,处方PPI的患者与未处方PPI的患者具有根本不同的表型，一种通过指示混淆的形式，在解释研究和对其使用提出建议时，应强烈考虑这一点。
■惠康信托基金和卫生与社会护理部。
■在对ATTIRE试验的事后分析中，我们汇集了所有患者数据,以研究PPI使用对临床结局的影响.ATTIRE是一个多中心,开放标签，针对20％人白蛋白溶液（HAS）每日输注与标准治疗的随机试验，涉及777例失代偿性肝硬化成人，因急性并发症和白蛋白<30g/L住院研究招募时间为2016年1月25日至2019年6月28日，在英格兰35家医院进行，苏格兰,威尔士。关键排除标准是预期寿命<8周的晚期肝细胞癌和接受姑息治疗的患者。在ATTIRE,患者在进入试验时按PPI使用情况分组.我们研究了基线时的感染和HE以及医院获得性感染的发生率，新发作的他，肾功能不全和死亡率。我们尝试用倾向评分匹配来解释疾病严重程度的差异。
■基线时使用总PPI与感染发生率增加无关，肾功能障碍或死亡率，但与住院期间III/IV级HE发生率显著增加相关(P=0.011).这仅对那些服用静脉PPI的患者有意义，与非PPI患者相比，这些患者静脉曲张破裂出血的发生率>10倍，28天死亡率接近两倍。然而,倾向评分匹配是不可能的，因为PPI使用的患者选择如此强烈，我们找不到足够的非PPI患者来匹配。我们发现使用PPI对细菌易位的血浆标志物没有影响，感染或全身性炎症。
■我们从完成的随机试验中获得的实际数据表明，PPI在英国被广泛开处方，合理使用对失代偿期肝硬化住院患者似乎是安全的。然而,处方PPI的患者与未处方PPI的患者具有根本不同的表型，一种通过指示混淆的形式，在解释研究和对其使用提出建议时，应强烈考虑这一点。
■惠康信托基金和卫生与社会护理部。
