A Clinical Study Of Entecavir Treatment In Patients With HBV Related Acute-On-Chronic Liver Failure

BackgroundHepatitis B related acute-on-chronic liver failure has a poor prognosis with very high mortality. Unfortunately, most prognostic predictive models of liver failure are complicated and offer suboptimal sensitivity. Experience in entecavir-treated patients with HBV-ACLF is limited.AimThis study was designed to evaluate the efficacy and safety of entecavir in patients with HBV-ACLF and to develop a novel model (Tongji prognostic predictor model, TPPM) for prognostic prediction of HBV-ACLF patients.Method In this retrospective study,248 patients with HBV-ACLF were enrolled. One hundred and twenty four patients received standard internal medications and additional Entecavir treatment, and the remaining 124 patients only received standard internal medications without nucleoside analogues (NA) for virus inhibition. There were no significant differences in baseline clinical and virological characteristics between patients treated with and without entecavir. Patients survival, biochemical markers of TP, ALB, ALT, AST, TBil, DBil, Tchol, CHE, Urea, SCr, coagulation capacity (INR, prothrombin time, prothrombin activity), blood routine examination (WBC, N, RBC, HGB, PLT), serology markers of HBsAg, HBsAb, HBeAg, HBeAb, HBcAb, virological markers of HBV-DNA and complications were monitored and included in the multivariate logistic regression analysis based on which the regression model for prognostic prediction (Tongji prognostic predictory model, TPPM) was established.ResultsThe 1 and 3-monthly survival rates of patients in Entecavir treated group was 72.58% (90/124) and 61.29%(76/124), significantly higher than that in NA free group which was only 53.23%(66/124) and 45.97%(57/124) (x2=9.953 P=0.002, x2=5.853 F=0.022, respectively). Entecavir treated group also achieved a better improvement of MELD score when compared with the controls (21.02±11.28 versus 25.13±11.62, P=0.007). On multivariate logistic regression, high INR for prothrombin time (odds ratio 2.589,95%CI 1.501-4.465),>2 Complications (odds ratio 9.568,95%CI 4.319-21.197) and high total bilirubin (odds ratio 1.003,95%CI 1.001-1.005) but not HBV DNA were independent predictors of liver-related mortality. By Hosmer and Lemeshow test, these biomarkers together were constituted a novel Tongji Prognostic Predictory Model (TPPM) for HBV-ACLF with a very good degree fit with disease prognosis (x2 value=28.959, P<0.001). Based on this unique group of patients data base, further analysis of AUC and AUC comparison demonstrated that the TPPM scoring owned better prediction value in specificity and sensitivity (94.7,89.6, respectively) for 3-monthly mortality of patients with HBV-ACLF compare with MELD scoring system (Specificity=90.2, Sensitivity=87.8), the AUC of TPPM were 0.970 (P< 0.001,95%CI 0.941-0.988) and of MELD 0.940 (P <0.001,95%CI 0.903-0.966), with significantly difference (Zstatistic= 2.428, P= 0.015). In the patients with HBV-ACLF, using a cutoff of 0.22 for 3-monthly predicted mortality by TPPM, the positive predictive value was 93.6%, and negative predictive value 91.3%.ConclusionEntecavir treatment prevented disease progression and increased the survival of patients with HBV-ACLF. The established TPPM scoring system offers superior predictor value in both specificity and sensitivity for HBV-ACLF patients when compared with MELD.