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Development and validation of a dynamic survival prediction model for patients with acute-on-chronic liver failure


ABSTRACT:

Background & Aims

Acute-on-chronic liver failure (ACLF) is usually associated with a precipitating event and results in the failure of other organ systems and high short-term mortality. Current prediction models fail to adequately estimate prognosis and need for liver transplantation (LT) in ACLF. This study develops and validates a dynamic prediction model for patients with ACLF that uses both longitudinal and survival data.

Methods

Adult patients on the UNOS waitlist for LT between 11.01.2016-31.12.2019 were included. Repeated model for end-stage liver disease-sodium (MELD-Na) measurements were jointly modelled with Cox survival analysis to develop the ACLF joint model (ACLF-JM). Model validation was carried out using separate testing data with area under curve (AUC) and prediction errors. An online ACLF-JM tool was created for clinical application.

Results

In total, 30,533 patients were included. ACLF grade 1 to 3 was present in 16.4%, 10.4% and 6.2% of patients, respectively. The ACLF-JM predicted survival significantly (p <0.001) better than the MELD-Na score, both at baseline and during follow-up. For 28- and 90-day predictions, ACLF-JM AUCs ranged between 0.840-0.871 and 0.833-875, respectively. Compared to MELD-Na, AUCs and prediction errors were improved by 23.1%-62.0% and 5%-37.6% respectively. Also, the ACLF-JM could have prioritized patients with relatively low MELD-Na scores but with a 4-fold higher rate of waiting list mortality.

Conclusions

The ACLF-JM dynamically predicts outcome based on current and past disease severity. Prediction performance is excellent over time, even in patients with ACLF-3. Therefore, the ACLF-JM could be used as a clinical tool in the evaluation of prognosis and treatment in patients with ACLF.

Lay summary

Acute-on-chronic liver failure (ACLF) progresses rapidly and often leads to death. Liver transplantation is used as a treatment and the sickest patients are treated first. In this study, we develop a model that predicts survival in ACLF and we show that the newly developed model performs better than the currently used model for ranking patients on the liver transplant waiting list. Graphical abstract Highlights • ACLF is a dynamic disease that can rapidly change over time, which greatly influences patient survival without LT.• Currently, the MELD-Na score is used to prioritize patients for LT, but MELD-Na underestimates ACLF disease severity.• The ACLF joint model (ACLF-JM) was developed to dynamically predict survival.• The ACLF-JM significantly outperformed the MELD-Na score for the prediction of mortality on the LT waiting list.• The ACLF-JM can be used online to predict survival in individual patients.

SUBMITTER: Goudsmit B 

PROVIDER: S-EPMC8570961 | biostudies-literature |

REPOSITORIES: biostudies-literature

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