■肝硬化相关免疫功能障碍(CAID)影响先天和适应性免疫。本研究调查了互补系统,免疫球蛋白,和急性期蛋白及其与晚期慢性肝病(ACLD)患者预后的相关性。
■患有ACLD(肝静脉压力梯度[HVPG]≥6mmHg)但没有急性代偿失调/感染的患者以HVPG和临床EASL分期为特征:补偿(cACLD;S0-2)与失代偿性ACLD(dACLD)伴既往静脉曲张出血(S3),非出血代偿(S4),或进一步失代偿(S5)。补充因子(C3c,C4,CH50),免疫球蛋白(IgA,IgM,IgG,IgG1-4),急性期蛋白和全身性炎症生物标志物(白细胞,C反应蛋白,测量IL-6,降钙素原)。
■共有245名患者(终末期肝病评分模型中位数:11[9-15],中位数HVPG:17[12-21]mmHg)包括150(61%)的dACLD。在dACLD子S4和S5中补体水平和活性显著降低(p<0.001)。dACLD患者总IgA/IgM/IgG和IgG1-4亚型水平升高(均p<0.05)。补体和免疫球蛋白水平呈负相关和正相关,分别,全身性炎症(均p<0.05)。高IgG-1(每100mg/dl调整后的风险比:1.12,1.04-1.19,p=0.002)和IL-6(调整后的风险比:1.03,1.00-1.05,p=0.023)水平预测了感染的发展。高IgA(按中位数分层;对数秩p<0.001),高IgG1(log-rankp=0.043)和低C3c(log-rankp=0.003)表明首次/进一步失代偿或肝脏相关死亡(复合终点)的风险较高.在多变量Cox回归分析中,除了HVPG和IL-6之外,低C3c(调整后的每mg/dl风险比:0.99,0.97-0.99,p=0.040)仍然与复合终点独立相关。
■补体水平和免疫球蛋白可作为肝硬化相关免疫功能障碍的替代指标,并与肝硬化严重程度和全身性炎症相关。低补体C3c预测失代偿和肝脏相关死亡,而高IgG-1表明感染风险增加。
■肝硬化患者感染风险增加,这恶化了他们的预后。我们发现与疾病严重程度有关的免疫系统的几个基本组成部分的显着失调,并表明感染和其他并发症的风险。简单的血液检查可以识别出特别高风险的患者,谁可能是预防措施的候选人。
■本研究在ClinicalTrials.gov(NCT03267615)注册。
UNASSIGNED: Cirrhosis-associated immune dysfunction (CAID) affects both innate and adaptive immunity. This study investigated the complement system, immunoglobulins, and acute-phase proteins and their prognostic relevance in patients with advanced chronic liver disease (
ACLD).
UNASSIGNED: Patients with
ACLD (hepatic venous pressure gradient [HVPG] ≥6 mmHg) but without acute decompensation/infections were characterised by HVPG and by clinical EASL stages: compensated (cACLD; S0-2) vs. decompensated
ACLD (dACLD) with previous variceal bleeding (S3), non-bleeding decompensation (S4), or further decompensation (S5). Complement factors (C3c, C4, CH50), immunoglobulins (IgA, IgM, IgG, IgG1-4), acute-phase proteins and systemic inflammation biomarkers (white blood cells, C-reactive protein, IL-6, procalcitonin) were measured.
UNASSIGNED: A total of 245 patients (median model for end-stage liver disease score: 11 [9-15], median HVPG: 17 [12-21] mmHg) were included with 150 (61%) presenting dACLD. Complement levels and activity significantly decreased in dACLD substages S4 and S5 (p <0.001). Total IgA/IgM/IgG and IgG1-4 subtype levels increased in patients with dACLD (all p <0.05). Complement and immunoglobulin levels correlated negatively and positively, respectively, with systemic inflammation (all p <0.05). High IgG-1 (adjusted hazard ratio per 100 mg/dl: 1.12, 1.04-1.19, p = 0.002) and IL-6 (adjusted hazard ratio: 1.03, 1.00-1.05, p = 0.023) levels predicted the development of infections during follow-up. High IgA (stratified by median; log-rank p <0.001), high IgG1 (log-rank p = 0.043) and low C3c (log-rank p = 0.003) indicated a higher risk of first/further decompensation or liver-related death (composite endpoint). Next to HVPG and IL-6, low C3c (adjusted hazard ratio per mg/dl: 0.99, 0.97-0.99, p = 0.040) remained independently associated with the composite endpoint on multivariate Cox regression analysis.
UNASSIGNED: Complement levels and immunoglobulins may serve as surrogates of cirrhosis-associated immune dysfunction and associate with cirrhosis severity and systemic inflammation. Low complement C3c predicted decompensation and liver-related death, whereas high IgG-1 indicated an increased risk for infections.
UNASSIGNED: Patients with cirrhosis are at increased risk for infections, which worsen their prognosis. We found a significant dysregulation of several essential components of the immune system that was linked to disease severity and indicated a risk for infections and other complications. Simple blood tests identify patients at particularly high risk, who may be candidates for preventive measures.
UNASSIGNED: This study is registered at ClinicalTrials.gov (NCT03267615).