2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Liver Int. 2019 Feb;39(2):299-306. doi: 10.1111/liv.13977. Epub 2018 Oct 24.
BACKGROUND & AIM: Human beta-defensin-1 (hBD-1) is a natural antimicrobial peptide expressed in the epithelia of multiple tissues including the digestive tract. In the current study, hBD-1 levels were determined in different subsets of patients with decompensated cirrhosis including acute-on-chronic liver failure (ACLF). In addition, the association with mortality of hBD-1, C-reactive protein (CRP) and procalcitonin (PCT) was assessed.
A total of 125 patients were divided into three groups: 39 with ACLF (derivation cohort), 46 with acute decompensation without ACLF (AD) and 40 with decompensated cirrhosis without an acute event (DC). The data from 24 different ACLF patients were used for validation and 15 healthy individuals as control group.
Serum hBD-1, CRP and PCT levels were higher in ACLF compared to both AD and DC groups (P < 0.001). Healthy controls demonstrated similar hBD-1 and PCT values compared to DC group. In ROC curve, the performance of hBD-1 to predict 60-day mortality in ACLF group was similar in derivation and validation cohorts (c-statistic 0.834 and 0.879, respectively). CRP was a poor predictor of mortality. In ACLF group, patients with high hBD-1 (>36.625 ng/mL) had a poor prognosis at 60 days compared to those with lower values (log-rank P = 0.001). In Cox multivariate regression analysis, only hBD-1 (HR 1.020, 95%CI 1.006-1.035, P = 0.006) emerged as an independent predictor of death in ACLF group. In AD group, neither hBD-1 nor PCT or CRP variables were associated with mortality.
High hBD-1 was detected at presentation in patients with ACLF who died during follow-up period. hBD-1 is an accurate predictor of short-term mortality in patients with ACLF.
人β防御素-1（hBD-1）是一种天然抗菌肽，在包括消化道在内的多种组织的上皮细胞中表达。在本研究中，测定了失代偿性肝硬化患者的不同亚组中 hBD-1 的水平，包括慢加急性肝衰竭（ACLF）。此外，评估了 hBD-1、C 反应蛋白（CRP）和降钙素原（PCT）与死亡率的相关性。
共纳入 125 例患者，分为三组：39 例 ACLF（推导队列），46 例急性失代偿但无 ACLF（AD），40 例失代偿性肝硬化但无急性事件（DC）。24 例不同 ACLF 患者的数据用于验证，15 例健康个体作为对照组。
ACLF 患者血清 hBD-1、CRP 和 PCT 水平均高于 AD 和 DC 组（P<0.001）。健康对照组与 DC 组的 hBD-1 和 PCT 值相似。在 ROC 曲线中，hBD-1 预测 ACLF 组 60 天死亡率的表现，在推导和验证队列中相似（曲线下面积分别为 0.834 和 0.879）。CRP 是死亡率的不良预测指标。在 ACLF 组中，hBD-1 水平较高（>36.625ng/mL）的患者在 60 天的预后较差，与 hBD-1 水平较低的患者相比（log-rank P=0.001）。在 Cox 多变量回归分析中，只有 hBD-1（HR 1.020，95%CI 1.006-1.035，P=0.006）是 ACLF 组死亡的独立预测因素。在 AD 组中，hBD-1、PCT 或 CRP 变量均与死亡率无关。
在随访期间死亡的 ACLF 患者在就诊时检测到高水平的 hBD-1。hBD-1 是 ACLF 患者短期死亡率的准确预测指标。
