ABSTRACT
Objective:To compare the prognostic accuracy of 16 pre-transplant scoring models in predicting the post-transplant short-term outcome of patients with hepatitis B-related acute-on-chronic liver failure (HBACLF), and to explore an efficient predictive model.Methods:A retrospective analysis of the clinical data of HBACLF patients who underwent liver transplantation at the Liver Transplant Center of Beijing Youan Hospital from August 2004 to September 2014. Score of 16 models (CTP, UNOS-MELD, Updated-MELD, Integrated-MELD, MELD-Na, MLED Na, CLIF-SOFA, CLIF-OFs, CLIF-C ACLFs, CLIF-C ADs, Refit MELD, Refit MELD Na, MELD-AS, Zheng's Risk, UKELD, MESO) was based on time-dependent operation characteristic curve, and the area under the curve (AUC) was calculated to evaluate the prediction accuracy of 3-month survival after transplantation. Selection of univariate factors associated with postoperative short-term mortality was performed, and then 16 scoring models one by one with statistically significant mortality-related factors were entered into LASSO regression (Least Absolute Shrinkage and Selection Operator regression) to confirm the independent variables. Finally, a predictive model was constructed by Cox regression.Results:A total of 135 patients were included in this study, including 106 males and 29 females, aged (45.0±10.5) years old. Among the 16 scoring models, the AUC of MELD-Na and CLIF-SOFA were more than 0.7 in early survival prediction after liver transplant. The MELD-Na was confirmed as an independent predictive variable in the final model with univariate and LASSO regression multivariate selection analysis ( HR=1.0481, 95% CI: 1.0136-1.0838, P<0.05). The model was constructed by MELD-Na and combined with other clinical parameters (female, systemic infection, placement of T tube during operation) could better predict the early survival after liver transplant. The overall C-index of the final model was 0.886, and the C-index at 3-month after liver transplant was 0.844 through internal validation (Bootstrap). Conclusion:Compared with other scoring models, MELD-Na and CLIF-SOFA were better for early survival prediction after liver transplantation for patients with HBACLF. The constructed predictive model based on MELD-Na was superior than single MELD-Na or CLIF-SOFA in prognostic assessment and case selection.
ABSTRACT
Objective@#To investigate the risk factors affecting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), and establish a new scoring model to predict the short-term prognosis of patients.@*Methods@#This study enrolled 222 patients with HBV-ACLF. According to their clinical outcomes during hospitalization and 90 days after discharge, they were divided into survival and death group. Clinical data were collected to calculate the Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), albumin-bilirubin (ALBI), and age-bilirubin-international normalized ratio-creatinine (ABIC) scores for prognosis. Multivariate logistic regression analysis was used to analyze the independent risk factors affecting 90-day mortality in HBV-ACLF patients. Cox regression model was used to establish a new prediction model. Area under the receiver operating characteristic curve was used to calculate short-term prognostic value of the models. K-M survival curve was used to predict the prognosis of patients.@*Results@#CTP and ABIC scores were independent risk factors for 90-day mortality in HBV-ACLF patients, and the risk of death from liver failure had increased with increase of score. Cox regression model established a new predictive model CTP-ABIC = 0.551 × CTP + 0.297 × ABIC. Area under the receiver operating characteristic curve of all three scoring models (CTP, ABIC and CTP-ABIC) were 0.878, 0.829, 0.927, respectively. CTP-ABIC score was superior to the CTP and ABIC score (P value < 0.001). Patients with CTP-ABIC score ≥9.08 had higher mortality rate than patients with CTP-ABIC score < 9.08, and the difference was statistically significant (P < 0.001).@*Conclusion@#All three scoring systems can predict short-term prognosis in patients with HBV-ACLF, but the accuracy of CTP-ABIC is superior.
ABSTRACT
Immune-mediated inflammatory injury is an important feature of the disease aggravation of hepatitis B virus-related acute-on-chronic liver failure (ACLF). Toll-like receptors (TLRs) have been shown previously to play a pivotal role in the activation of innate immunity. The purpose of this study was to characterize the TLR4 expression in peripheral blood mononuclear cells (PBMCs) of ACLF patients and its possible role in the disease aggravation. Twelve healthy subjects, 15 chronic HBV-infected (CHB) patients and 15 ACLF patients were enrolled in this study. The TLR4 expression in PBMCs and T cells of all subjects was examined by real-time PCR and flow cytometry. The correlation of TLR4 expression on T cells with the markers of disease aggravation was evaluated in ACLF patients. The ability of TLR4 ligands stimulation to induce inflammatory cytokine production in ACLF patients was analyzed by flow cytometry. The results showed that TLR4 mRNA level was upregulated in PBMCs of ACLF patients compared to that in the healthy subjects and the CHB patients. Specifically, the expression of TLR4 on CD4(+) and CD8(+) T cells of PBMCs was significantly increased in ACLF patients. The TLR4 levels on CD4(+) and CD8(+) T cells were positively correlated with serum total bilirubin (TBIL), direct bilirubin (DBIL), international normalized ratio (INR) levels and white blood cells (WBCs), and negatively correlated with serum albumin (ALB) levels in the HBV-infected patients, indicating TLR4 pathway may play a role in the disease aggravation of ACLF. In vitro TLR4 ligand stimulation on PBMCs of ACLF patients induced a strong TNF-α production by CD4(+) T cells, which was also positively correlated with the serum markers for liver injury severity. It was concluded that TLR4 expression is upregulated on T cells in PBMCs, which is associated with the aggravation of ACLF.