# Development and validation of a prognostic model for acute-on-chronic liver failure

**Authors:** Xia Zhu, Ming Wang, Yuanji Ma, Libo Yan, Jianhao Li, Hong Peng, Yue Huang, Hong Tang

PMC · DOI: 10.3389/fcimb.2026.1759738 · Frontiers in Cellular and Infection Microbiology · 2026-02-09

## TL;DR

This study developed a machine learning model to predict 90-day mortality in patients with HBV-related acute-on-chronic liver failure, outperforming traditional scoring systems.

## Contribution

A novel machine learning model incorporating liver reserve function for improved prognosis in HBV-ACLF.

## Key findings

- The LASSO-RF model achieved an AUC of 0.99 in training and 0.98 in validation for predicting 90-day mortality.
- Liver reserve indicators like EHBF and ICG-R15 were key predictors in the model.
- An online tool was developed to provide real-time risk scores and mortality predictions.

## Abstract

Prognostic assessment in acute-on-chronic liver failure (ACLF), particularly in HBV-endemic regions, remains challenging due to the limited accuracy of conventional models. We aimed to develop and validate a novel, machine learning-based model incorporating liver reserve function to improve individualized prediction of short-term outcomes in HBV-ACLF.

Baseline demographics, clinical features, laboratory findings, and 90-day follow-up data were retrospectively collected from 496 patients (training/internal subgroups) and 52 patients (external validation) with HBV-ACLF. Twelve machine learning algorithms were systematically evaluated for prognostic performance. The optimal model was established using the LASSO-RF approach, with key variables identified by SHAP values. Model accuracy was assessed by ROC analysis and compared with MELD and CTP scores. An interactive web calculator (https://syx123.shinyapps.io/deploy_shiny/) was developed to facilitate clinical use.

We initially screened 23 potential clinical risk factors for predicting ACLF prognosis. Subsequently, using the LASSO-RF model, 15 key variables were selected for model construction. The final LASSO-RF model achieved an AUC of 0.99 in the training cohort and 0.98 in the validation cohort for predicting 90-day mortality, outperforming conventional scoring systems such as MELD and CTP. To facilitate clinical application, an online tool (https://syx123.shinyapps.io/deploy_shiny/) was developed to provide real-time risk scores and 90-day mortality predictions for individual patients.

Liver reserve function indicators, particularly EHBF and ICG-R15, play a pivotal role in prognosticating HBV-ACLF outcomes. The developed model and its accompanying online tool enable accurate risk stratification and have the potential to guide timely and individualized clinical management.

## Full-text entities

- **Genes:** EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, SHROOM4 (shroom family member 4) [NCBI Gene 57477] {aka MRXSSDS, SHAP, shrm4}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}
- **Diseases:** Organ Failure (MESH:D009102), splenomegaly (MESH:D013163), CMV (MESH:D003586), jaundice (MESH:D007565), metabolic abnormalities (MESH:D008659), EBV (MESH:D020031), cirrhosis (MESH:D005355), Complications (MESH:D008107), inflammation (MESH:D007249), cirrhotic (MESH:D000094724), chronic alcohol abuse (MESH:D000437), impaired mitochondrial function (MESH:D028361), malignancies (MESH:D009369), AD (MESH:D000544), Hyponatremia (MESH:D007010), Hepatorenal syndrome (MESH:D006530), liver cirrhosis (MESH:D008103), NAD (MESH:D016111), abdominal infections (MESH:D000007), alcoholic liver injury (MESH:D008108), liver dysfunction (MESH:D017093), HE (MESH:D006501), hypokalemia (MESH:D007008), drug-induced liver injury (MESH:D056486), postoperative (MESH:D019106), CHB (MESH:D019694), immune dysregulation (OMIM:614878), HCC (MESH:D006528), Infectious Diseases (MESH:D003141), autoimmune hepatitis (MESH:D019693), ACLF (MESH:D065290), -Stage Liver Disease (MESH:D058625), ascites (MESH:D001201), Hypoproteinemia (MESH:D007019), co-infections (MESH:D060085), viral hepatitis (MESH:D014777), death (MESH:D003643), coagulation dysfunction (MESH:D001778), acute liver injury (MESH:D017114)
- **Chemicals:** NH3 (MESH:D000641), bilirubin (MESH:D001663), ICG-R15 (-), Na (MESH:D012964), potassium (MESH:D011188), ICG (MESH:D007208)
- **Species:** Human immunodeficiency virus 1 (no rank) [taxon 11676], hepatitis C virus [taxon 11103], Hepatitis delta virus (no rank) [taxon 12475], Hepatovirus A (no rank) [taxon 12092], hepatitis E virus [taxon 12461], Human immunodeficiency virus (species) [taxon 12721], Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12926412/full.md

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12926412/full.md

## References

29 references — full list in the complete paper: https://tomesphere.com/paper/PMC12926412/full.md

---
Source: https://tomesphere.com/paper/PMC12926412