Human beta‐defensin‐1 is a highly predictive marker of mortality in patients with acute‐on‐chronic liver failure

Abstract

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. Methods 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. Results 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. Conclusions 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.

Etiology of viral induced acute liver failure and defensins as potential therapeutic agents in ALF treatment

“…In turn, Zhong et al ( 97) reported that knock-out of a-defensins resulted in greater liver damage in a mouse model of alcoholic steatohepatitis, while administration of synthetic human adefensins 5 showed a therapeutic effect in this study. Mani et al (98) showed that the level of human b-defensin 1 was significantly elevated in patients with acute or chronic hepatic failure, indicating a strong predictive value as a marker of mortality. There are also reports indicating increased expression of a-defensin 4 in infections with hepatitis viruses, which, as described earlier, are associated with ALF.…”

The Editorial Position on ‘Recent Advances in Multifunctional Antimicrobial Peptides as Preclinical Therapeutic Studies and Clinical Future Applications’

“…Another important application for MF-AMPs in human health is their roles as the biomarkers of several diseases both related and unrelated to infections [28][29][30][31]. In this Special Issue, Scnheider and collaborators summarized the biomarker profile of CgA and its derived antimicrobial peptides in the context of critically ill patients [4].…”