A study on treatment timing selection and short-term efficacy prediction with changes in cytokine levels before and after non-biological artificial liver treatment in acute-on-chronic liver failure

Abstract

Objective: To investigate the efficacy and diagnostic accuracy of changes in cytokine levels before and after non-biological artificial liver (referred to as ABL) treatment in patients with acute-on-chronic liver failure (ACLF) in order to establish a basis for treatment timing selection and short-term (28d) prognosis. Methods: 90 cases diagnosed with ACLF were selected and divided into a group receiving artificial liver treatment (45 cases) and a group not receiving artificial liver treatment (45 cases). Age, gender, first routine blood test after admission, liver and kidney function, and procalcitonin (PCT) of the two groups were collected. The 28-day survival of the two groups was followed-up for survival analysis. The 45 cases who received artificial liver therapy were further divided into an improvement group and a deterioration group according to the clinical manifestations before discharge and the last laboratory examination results as the efficacy evaluation indicators. Routine blood test, coagulation function, liver and kidney function, PCT, alpha fetoprotein (AFP), β-defensin-1 (HBD-1), 12 cytokines and other indicators were analyzed and compared. A receiver operating characteristic curve (ROC curve) was used to analyze the diagnostic efficacy of the short-term (28 d) prognosis and an independent risk factors affecting the prognosis of ACLF patients. According to different data, Kaplan-Meier method, log-rant test, t-test, Mann-Whitney U test, Wilcoxon rank-sum test, χ2 test, Spearman rank correlation analysis and logistic regression analysis were used for statistical analysis. Results: The 28-day survival rate was significantly higher in ACLF patients who received artificial liver therapy than that of those who did not receive artificial liver therapy (82.2% vs. 61.0%, P<0.05). The levels of serum HBD-1, alpha interferon (IFN-α) and interleukin-5 (IL-5) after artificial liver treatment were significantly lower in ACLF patients than those before treatment (P<0.05), while liver and coagulation function were significantly improved compared with those before treatment (P<0.05), and there was no statistically significant difference in other serological indexes before and after treatment (P＞0.05). Before artificial liver treatment, serum HBD-1 and INF-α levels were significantly lower in the ACLF improvement group than in the deterioration group (P<0.05) and were positively correlated with the patients' prognosis (deteriorating) (r=0.591, 0.427, P<0.001, 0.008). The level of AFP was significantly higher in the improved ACLF group than that in the deterioration group (P<0.05), and was negatively correlated with the prognosis (deteriorating) of the patients (r=-0.557, P<0.001). Univariate logistic regression analysis showed that HBD-1, IFN-α and AFP were independent risk factors for the prognosis of ACLF patients (P=0.001, 0.043, and 0.036, respectively), and that higher HBD-1 and IFN-α levels were associated with lower AFP level and a deteriorating prognosis. The area under the curve (AUC) of HBD-1, IFN-α, and AFP for short-term (28d) prognostic and diagnostic efficacy of ACLF patients was 0.883, 0.763, and 0.843, respectively, and the sensitivity and specificty was 0.75, 0.75, and 0.72, and 0.84, 0.80, and 0.83, respectively. The combination of HBD-1 and AFP had further improved the diagnostic efficiency of short-term prognosis of ACLF patients (AUC=0.960, sensitivity and specificity: 0.909 and 0.880 respectively). The combination of HBD-1+IFN-α+AFP had the highest diagnostic performance, with an AUC of 0.989, sensitivity of 0.900, and specificity of 0.947. Conclusion: Artificial liver therapy can effectively improve the clinical symptoms and liver and coagulation function of patients with ACLF; remove cytokines such as HBD-1, IFN-α, and IL-5 in patients with liver failure; delay or reverse the progression of the disease; and improve the survival rate of patients. HBD-1, IFN-α, and AFP are independent risk factors affecting the prognosis of ACLF patients, which can be used as biological indicators for evaluating the short-term prognosis of ACLF patients. The higher the level of HBD-1 and/or IFN-α, the higher the risk of disease deterioration. Therefore, artificial liver therapy should be started as soon as possible after the exclusion of infection. In diagnosing the prognosis of ACLF, HBD-1 has higher sensitivity and specificity than IFN-α and AFP, and its diagnostic efficiency is greatest when combined with IFN-α and AFP.