| Background & AimAcute on chronic hepatitis B liver failure (ACHBLF) is a serious disease with high mortality. It has been recently reported that wnt signaling was involved in inflammation, which plays important role in the pathogenesis of ACHBLF. In our study, we intended to detect the expression profile of some wnt signaling molecules and aimed to find out a predictor for the prognosis of ACHBLF.Patients and MethodsA total of 153 participants were enrolled in this study, including 63 patients with ACHBLF,60 patients with chronic hepatitis B (CHB) and 30 health controls (HCs). We determined the mRNA levels of wnt5a, wnt3a, lefl, tcfl, fzd5 and sfrpl in peripheral mononuclear cells (PBMCs) by real-time PCR. The methylation status of sfrpl promoter was evaluated by methylation-specific PCR. Serum wnt5a and sfrpl concentration was measured with the use of enzyme-linked immunosorbent assay(ELISA). The data were analyzed with SPSS version 16.0 (Chicago, IL, USA). Data were expressed as the median (centile 25; centile 75) or number. Comparison of clinical characteristics between groups was analyzed by the Mann-Whitney U test, Student’s t test or Chi-square test. Correlation between serum wnt5a and other parameters was calculated using Spearman rank correlation.Results1. Wnt5a mRNA level was higher in patients with ACHBLF than those with CHB (P=0.010) and HCs (P<0.001). Meanwhile, wnt5a mRNA was also elevated in CHB group compared with HCs group (P=0.037).2. Serum wnt5a concentration was also elevated in patients with ACHBLF [1.59 (1.43-3.22) ng/ml] compared with those with CHB [1.47 (1.42-1.54) ng/ml, P=0.046] and HCs [1.44 (1.41-1.48) ng/ml, P=0.023]. There was no significant difference in serum wnt5a concentration between CHB and HCs group (P=0.259).3. Serum wnt5a in patients with ACHBLF was positively correlated with total bilirubin (TBIL) (rs=0.277, P=0.028), creatinine (Cr) (rs=0.312, 0.013) and model for end-stage liver diseases (MELD) score (rs=0.444, P<0.001). Wnt5a was, by contrast, negatively correlated with alanine aminotransferase (ALT) (rs=-0.27, P=0.032) and albumin (ALB) (rs=-0.254, P=0.044). No significant correlations were found between serum wnt5a and other parameters, such as HBV-DNA, aspartate aminotransferase (AST), international normalized ratio (INR) or prothrombin time activity (PTA).4. A cut-off value of 1.553 ng/ml for wnt5a was optimal with a sensitivity of 69.23%, a specificity of 83.33%, a positive predictive value of 87.1% and a negative predictive value of 62.5% to predict the prognosis of ACHBLF. The area under the receiver operating characteristic curve (AUC) for wnt5a was 0.847 (95% CI:0.734-0.925). The mean survival time for patients with ACHBLF with serum wnt5a ≥1.553 and<1.553 ng/ml were 26.594 ± 5.267 (95% CI:16.271-6.916) days and 65.032 ± 5.901[(95% CI:53.467-76.598) days, P< 0.001)], respectively.5. Patients with ACHBLF (22/63,34.9%) had lower ratios of sfrpl promoter methylation than those with CHB (37/60,61.7%; P=0.003), but higher ratios than HCs (2/30,6.7%; P<0.001).The sfrp1 mRNA was higher in patients with ACHBLF than that in patients with CHB (P=0.019), but lower than that in HCs (P=0.010). Serum sfrpl concentration in patients with ACHBLF [0.90 (0.57-1.58) ng/ml was high compared with those with CHB [0.56 (0.48-0.74) ng/ml, P<0.001], but it has no difference with that in HCs [0.73 (0.50-1.45), P=0.435].Conclusion1. We firstly demonstrated that serum wnt5a concentration was dramatically higher in patients with ACHBLF than that in patients with CHB and HCs, as well as higher in death patients than that in survival ones. It indicated that wnt5a might be a potential predictor to evaluate the 3-month prognosis for the patients with ACHBLF.2. Wnt5a and sfrpl were unregulated in patients with ACHBLF, which indicated that they might be involved in the pathogenesis of ACHBLF. |
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