PDF(Pubmed)
Abstract：
UNASSIGNED: Ammonia levels predicted hospitalisation in a recent landmark study not accounting for portal hypertension and systemic inflammation severity. We investigated (i) the prognostic value of venous ammonia levels (outcome cohort) for liver-related outcomes while accounting for these factors and (ii) its correlation with key disease-driving mechanisms (biomarker cohort).
UNASSIGNED: (i) The outcome cohort included 549 clinically stable outpatients with evidence of advanced chronic liver disease. (ii) The partly overlapping biomarker cohort comprised 193 individuals, recruited from the prospective Vienna Cirrhosis Study (VICIS: NCT03267615).
UNASSIGNED: (i) In the outcome cohort, ammonia increased across clinical stages as well as hepatic venous pressure gradient and United Network for Organ Sharing model for end-stage liver disease (2016) strata and were independently linked with diabetes. Ammonia was associated with liver-related death, even after multivariable adjustment (adjusted hazard ratio [aHR]: 1.05 [95% CI: 1.00-1.10]; p = 0.044). The recently proposed cut-off (≥1.4 × upper limit of normal) was independently predictive of hepatic decompensation (aHR: 2.08 [95% CI: 1.35-3.22]; p <0.001), non-elective liver-related hospitalisation (aHR: 1.86 [95% CI: 1.17-2.95]; p = 0.008), and - in those with decompensated advanced chronic liver disease - acute-on-chronic liver failure (aHR: 1.71 [95% CI: 1.05-2.80]; p = 0.031). (ii) Besides hepatic venous pressure gradient, venous ammonia was correlated with markers of endothelial dysfunction and liver fibrogenesis/matrix remodelling in the biomarker cohort.
UNASSIGNED: Venous ammonia predicts hepatic decompensation, non-elective liver-related hospitalisation, acute-on-chronic liver failure, and liver-related death, independently of established prognostic indicators including C-reactive protein and hepatic venous pressure gradient. Although venous ammonia is linked with several key disease-driving mechanisms, its prognostic value is not explained by associated hepatic dysfunction, systemic inflammation, or portal hypertension severity, suggesting direct toxicity.
UNASSIGNED: A recent landmark study linked ammonia levels (a simple blood test) with hospitalisation/death in individuals with clinically stable cirrhosis. Our study extends the prognostic value of venous ammonia to other important liver-related complications. Although venous ammonia is linked with several key disease-driving mechanisms, they do not fully explain its prognostic value. This supports the concept of direct ammonia toxicity and ammonia-lowering drugs as disease-modifying treatment.
UNASSIGNED: (i) The outcome cohort included 549 clinically stable outpatients with evidence of advanced chronic liver disease. (ii) The partly overlapping biomarker cohort comprised 193 individuals, recruited from the prospective Vienna Cirrhosis Study (VICIS: NCT03267615).
UNASSIGNED: (i) In the outcome cohort, ammonia increased across clinical stages as well as hepatic venous pressure gradient and United Network for Organ Sharing model for end-stage liver disease (2016) strata and were independently linked with diabetes. Ammonia was associated with liver-related death, even after multivariable adjustment (adjusted hazard ratio [aHR]: 1.05 [95% CI: 1.00-1.10]; p = 0.044). The recently proposed cut-off (≥1.4 × upper limit of normal) was independently predictive of hepatic decompensation (aHR: 2.08 [95% CI: 1.35-3.22]; p <0.001), non-elective liver-related hospitalisation (aHR: 1.86 [95% CI: 1.17-2.95]; p = 0.008), and - in those with decompensated advanced chronic liver disease - acute-on-chronic liver failure (aHR: 1.71 [95% CI: 1.05-2.80]; p = 0.031). (ii) Besides hepatic venous pressure gradient, venous ammonia was correlated with markers of endothelial dysfunction and liver fibrogenesis/matrix remodelling in the biomarker cohort.
UNASSIGNED: Venous ammonia predicts hepatic decompensation, non-elective liver-related hospitalisation, acute-on-chronic liver failure, and liver-related death, independently of established prognostic indicators including C-reactive protein and hepatic venous pressure gradient. Although venous ammonia is linked with several key disease-driving mechanisms, its prognostic value is not explained by associated hepatic dysfunction, systemic inflammation, or portal hypertension severity, suggesting direct toxicity.
UNASSIGNED: A recent landmark study linked ammonia levels (a simple blood test) with hospitalisation/death in individuals with clinically stable cirrhosis. Our study extends the prognostic value of venous ammonia to other important liver-related complications. Although venous ammonia is linked with several key disease-driving mechanisms, they do not fully explain its prognostic value. This supports the concept of direct ammonia toxicity and ammonia-lowering drugs as disease-modifying treatment.
摘要：
未经证实：在一项近期具有里程碑意义的研究中，氨水平预测了住院情况，但未考虑门脉高压和全身炎症严重程度。我们调查了（i）静脉氨水平（结果队列）对肝脏相关结果的预后价值，同时考虑了这些因素，以及（ii）其与关键疾病驱动机制（生物标志物队列）的相关性。
UNASSIGNED：（i）结局队列包括549名临床稳定的门诊患者，有晚期慢性肝病的证据。（ii）部分重叠的生物标志物队列包括193个个体，招募自前瞻性维也纳肝硬化研究（VICIS：NCT03267615）。
未经评估：（i）在结果队列中，氨在临床阶段以及肝静脉压力梯度和终末期肝病器官共享模型联合网络（2016年）分层增加，并且与糖尿病独立相关。氨与肝脏相关的死亡有关，即使经过多变量校正(校正后的风险比[aHR]:1.05[95%CI:1.00-1.10];p=0.044)。最近提出的截止值（≥1.4×正常上限）是肝功能失代偿的独立预测指标（aHR：2.08[95％CI：1.35-3.22]；p<0.001），非选择性肝脏相关住院（aHR：1.86[95%CI：1.17-2.95]；p=0.008），和-在失代偿期晚期慢性肝病患者中-慢性急性肝衰竭（aHR：1.71[95％CI：1.05-2.80]；p=0.031）。（ii）除了肝静脉压力梯度，在生物标志物队列中,静脉氨与内皮功能障碍和肝纤维化/基质重塑的标志物相关.
未经证实：静脉氨可预测肝脏失代偿，非选择性肝脏相关住院，慢性急性肝衰竭,和肝脏相关的死亡，独立于已建立的预后指标，包括C反应蛋白和肝静脉压力梯度。尽管静脉氨与几个关键的疾病驱动机制有关，其预后价值不能通过相关的肝功能障碍来解释，全身性炎症,或门脉高压的严重程度，提示直接毒性。
UNASSIGNED：最近一项具有里程碑意义的研究将氨水平（一种简单的血液检查）与临床稳定肝硬化患者的住院/死亡联系起来。我们的研究将静脉氨的预后价值扩展到其他重要的肝脏相关并发症。尽管静脉氨与几个关键的疾病驱动机制有关，他们不能完全解释其预后价值。这支持直接氨毒性和降氨药物作为疾病改善治疗的概念。
UNASSIGNED：（i）结局队列包括549名临床稳定的门诊患者，有晚期慢性肝病的证据。（ii）部分重叠的生物标志物队列包括193个个体，招募自前瞻性维也纳肝硬化研究（VICIS：NCT03267615）。
未经评估：（i）在结果队列中，氨在临床阶段以及肝静脉压力梯度和终末期肝病器官共享模型联合网络（2016年）分层增加，并且与糖尿病独立相关。氨与肝脏相关的死亡有关，即使经过多变量校正(校正后的风险比[aHR]:1.05[95%CI:1.00-1.10];p=0.044)。最近提出的截止值（≥1.4×正常上限）是肝功能失代偿的独立预测指标（aHR：2.08[95％CI：1.35-3.22]；p<0.001），非选择性肝脏相关住院（aHR：1.86[95%CI：1.17-2.95]；p=0.008），和-在失代偿期晚期慢性肝病患者中-慢性急性肝衰竭（aHR：1.71[95％CI：1.05-2.80]；p=0.031）。（ii）除了肝静脉压力梯度，在生物标志物队列中,静脉氨与内皮功能障碍和肝纤维化/基质重塑的标志物相关.
未经证实：静脉氨可预测肝脏失代偿，非选择性肝脏相关住院，慢性急性肝衰竭,和肝脏相关的死亡，独立于已建立的预后指标，包括C反应蛋白和肝静脉压力梯度。尽管静脉氨与几个关键的疾病驱动机制有关，其预后价值不能通过相关的肝功能障碍来解释，全身性炎症,或门脉高压的严重程度，提示直接毒性。
UNASSIGNED：最近一项具有里程碑意义的研究将氨水平（一种简单的血液检查）与临床稳定肝硬化患者的住院/死亡联系起来。我们的研究将静脉氨的预后价值扩展到其他重要的肝脏相关并发症。尽管静脉氨与几个关键的疾病驱动机制有关，他们不能完全解释其预后价值。这支持直接氨毒性和降氨药物作为疾病改善治疗的概念。
