■慢性急性肝衰竭(ACLF)的特征是器官衰竭,短期死亡率高,and,病理生理上,紊乱的炎症反应。细胞外基质(ECM)与炎症反应的调节密切相关。本研究旨在确定ACLF中ECM更新的生物标志物的改变及其与炎症的关联。器官衰竭,和死亡率。
■我们研究了283例因患有或不患有ACLF的急性代偿失调(AD)而入院的肝硬化患者,64例稳定期肝硬化患者,和30个健康对照。一个验证队列(25ACLF,包括9名健康对照)。测量血浆PRO-C3、PRO-C4、PRO-C5、PRO-C6和PRO-C8(即III-VI型和VIII型胶原形成)以及C4M和C6M(即IV型和VI型胶原降解)。对肝脏活检进行PRO-C6的免疫组织化学(AD[n=7],ACLF[n=5])。进行竞争风险回归分析以探索具有28天和90天死亡率的ECM更新的生物标志物的预后价值。
■与AD相比,ACLF中的PRO-C3和PRO-C6增加(分别为p=0.089和p<0.001),而胶原降解标志物C4M和C6M相似。PRO-C3和PRO-C6均与肝功能和炎症标志物密切相关。仅PRO-C6与肝外器官衰竭和28天和90天死亡率相关(风险比[HR;对数标度]6.168,95%CI2.366-16.080,p<0.001,和3.495,95%CI1.509-8.093,p=0.003,分别)。这些发现在验证队列中是一致的。在ACLF患者的肝活检中观察到高PRO-C6表达。
■这项研究表明,第一次,ACLF中严重的间质胶原净沉积的证据,并对PRO-C6与(肝外)器官衰竭和死亡率之间的关联进行了新的观察。需要进一步的研究来确定这些观察的致病意义。
■本研究描述了在慢性急性肝衰竭(ACLF)中III型和VI型胶原蛋白的更新中断。这些胶原蛋白的血浆生物标志物(PRO-C3和PRO-C6)与肝功能障碍和炎症的严重程度有关。PRO-C6,也称为激素内毒素,还发现与急性代偿失调和ACLF的多器官功能衰竭和预后有关。
UNASSIGNED: Acute-on-chronic liver failure (ACLF) is characterised by organ failure(s), high short-term mortality, and, pathophysiologically, deranged inflammatory responses. The extracellular matrix (ECM) is critically involved in regulating the inflammatory response. This study aimed to determine alterations in biomarkers of ECM turnover in ACLF and their association with inflammation, organ failures, and mortality.
UNASSIGNED: We studied 283 patients with cirrhosis admitted for acute decompensation (AD) with or without ACLF, 64 patients with stable cirrhosis, and 30 healthy controls. A validation cohort (25 ACLF, 9 healthy controls) was included. Plasma PRO-C3, PRO-C4, PRO-C5, PRO-C6, and PRO-C8 (i.e. collagen type III-VI and VIII formation) and C4M and C6M (i.e. collagen type IV and VI degradation) were measured. Immunohistochemistry of PRO-C6 was performed on liver biopsies (AD [n = 7], ACLF [n = 5]). A competing-risk regression analysis was performed to explore the prognostic value of biomarkers of ECM turnover with 28- and 90-day mortality.
UNASSIGNED: PRO-C3 and PRO-C6 were increased in ACLF compared to AD (p = 0.089 and p <0.001, respectively), whereas collagen degradation markers C4M and C6M were similar. Both PRO-C3 and PRO-C6 were strongly associated with liver function and inflammatory markers. Only PRO-C6 was associated with extrahepatic organ failures and 28- and 90-day mortality (hazard ratio [HR; on log-scale] 6.168, 95% CI 2.366-16.080, p <0.001, and 3.495, 95% CI 1.509-8.093, p = 0.003, respectively). These findings were consistent in the validation cohort. High PRO-C6 expression was observed in liver biopsies of patients with ACLF.
UNASSIGNED: This study shows, for the first time, evidence of severe net interstitial collagen deposition in ACLF and makes the novel observation of the association between PRO-C6 and (extrahepatic) organ failures and mortality. Further studies are needed to define the pathogenic significance of these observations.
UNASSIGNED: This study describes a disrupted turnover of collagen type III and VI in Acute-on-chronic liver failure (ACLF). Plasma biomarkers of these collagens (PRO-C3 and PRO-C6) are associated with the severity of liver dysfunction and inflammation. PRO-C6, also known as the hormone endotrophin, has also been found to be associated with multi-organ failure and prognosis in acute decompensation and ACLF.