Dynamic inflammation-based prognostication in acute-on-chronic liver failure: The COSSH-CAR model as a step forward in personalized risk stratification

Abstract

Acute-on-chronic liver failure (ACLF) is a swiftly deteriorating condition characterized by profound systemic inflammation and failure of multiple organ systems, leading to high early mortality. There remains a critical need for more effective biomarkers to facilitate timely and accurate risk assessment. Recent findings by Zhu and Yan demonstrated that evaluating temporal changes in the C-reactive protein to albumin ratio (CAR), especially the 7-day variation, offers superior prediction of 28-day mortality compared with single baseline measurements. By integrating the 7-day variation of CAR with the model for end-stage liver disease sodium score and the grade of hepatic encephalopathy, the Chinese Group on Study of Severe Hepatitis B (COSSH)-CAR model was created, which surpassed traditional prognostic tools such as the Child-Pugh, model for end-stage liver disease, and COSSH-ACLF. This comment highlights the importance of using dynamic biomarker trajectories rather than static values for prognostic evaluation. CAR is biologically compelling because it captures both the inflammatory burden and the patient’s nutritional/physiological reserve. While the COSSH-CAR model is promising and based on routinely obtainable laboratory data, its widespread adoption will depend on validation in larger, diverse, and non-hepatitis B virus-related cohorts. Future work should examine CAR kinetics in prospective and interventional studies and consider how they may support individualized management strategies. Collectively, these observations suggest that the CAR could represent an important addition to current ACLF prognostic frameworks.

Keywords: Acute-on-chronic liver failure; C-reactive protein to albumin ratio (CAR); Chinese Group on Study of Severe Hepatitis B-CAR; Dynamic biomarkers; Systemic inflammation; Hepatic encephalopathy; Risk stratification

Core Tip: The dynamic shift in the C-reactive protein to albumin ratio (CAR) during the initial week provides additional prognostic insight into Chinese Group on Study of Severe Hepatitis B-defined acute-on-chronic liver failure, surpassing the predictive capacity of traditional indices such as the model for end-stage liver disease sodium score and hepatic encephalopathy grade. Embedding 7-day variation of CAR within the Chinese Group on Study of Severe Hepatitis B-CAR score yields a biologically plausible, practical bedside instrument. Nonetheless, confirmation through robust, multicenter validation is essential before widespread clinical application can be recommended.