Abstract

Background: Patients with chronic hepatitis B (CHB) with severe acute exacerbation (SAE) are at a progression stage of acute-on-chronic liver failure (ACLF) but uniform models for predicting ACLF occurrence are lacking. We aimed to present a risk prediction model to early identify the patients at a high risk of ACLF and predict the survival of the patient.Methods: We selected the best variable combination using a novel recursive feature elimination algorithm to develop and validate a classification regression model and also an online application on a cloud server from the training cohort with a total of 342 patients with CHB with SAE and two external cohorts with a sample size of 96 and 65 patients, respectively.Findings: An excellent prediction model called the PATA model including four predictors, prothrombin time (PT), age, total bilirubin (Tbil), and alanine aminotransferase (ALT) could achieve an area under the receiver operating characteristic curve (AUC) of 0.959 (95% CI 0.941–0.977) in the development set, and AUC of 0.932 (95% CI 0.876–0.987) and 0.905 (95% CI 0.826–0.984) in the two external validation cohorts, respectively. The calibration curve for risk prediction probability of ACLF showed optimal agreement between prediction by PATA model and actual observation. After predictive stratification into different risk groups, the C-index of predictive 90-days mortality was 0.720 (0.675–0.765) for the PATA model, 0.549 (0.506–0.592) for the end-stage liver disease score model, and 0.648 (0.581–0.715) for Child–Turcotte–Pugh scoring system.Interpretation: The highlypredictive risk model and easy-to-use online application can accurately predict the risk of ACLF with a poor prognosis. They may facilitate risk communication and guidetherapeutic options.

Highlights

  • Chronic hepatitis B virus (HBV) infection poses a global health challenge [1]

  • We developed a logistic regression model for the optimal combination of variables selected by the Recursive feature elimination (RFE) algorithm and evaluated model performance using AUC, precision-recall (PR) curves, sensitivity, specificity, accuracy, positive predictive values (PPV), negative predictive values (NPV), and brier scores [31]

  • In the current study of 503 patients with chronic hepatitis B (CHB) with severe acute exacerbation (SAE) from three medical centers, by using the RFE algorithm, we developed and validated a novel risk prediction model for acuteon-chronic liver failure (ACLF) using prothrombin time (PT), age, TBil, and alanine aminotransferase (ALT)

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Summary

Introduction

Chronic hepatitis B virus (HBV) infection poses a global health challenge [1]. Hepatitis activity with alanine aminotransferase (ALT) elevation, called acute exacerbation or hepatitis flare, may occur spontaneously either over the natural course of the disease or following therapy among chronic HBV infection [2, 3]. Liver transplantation is the only effective treatment for ACLF, due to the high cost and shortage of liver source, only a small number of patients undergo liver transplantation [10]. In this situation, it is believed that early identification of the high risk of ACLF is of vital importance so that physicians can focus and intervene in advance to slow down or stop the progression of SAE to ACLF [9, 11, 12] and improve the prognosis of the patient. We aimed to present a risk prediction model to early identify the patients at a high risk of ACLF and predict the survival of the patient

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