Background & aims: Pre-acute-on-chronic liver failure (ACLF) is a distinct intermediate stage between acute decompensation (AD) and ACLF. However, identifying patients with pre-ACLF and predicting progression from AD to ACLF is difficult. This study aimed to identify pre-ACLF within 28 days, and to develop and validate a prediction model for ACLF in patients with HBV-related decompensated cirrhosis.
Methods: In total, 1,736 patients with HBV-related cirrhosis and AD were enrolled from 2 large-scale, multicenter, prospective cohorts. ACLF occurrence within 28 days, readmission, and 3-month and 1-year outcomes were collected.
Results: Among 970 patients with AD without ACLF in the derivation cohort, the 94 (9.6%) patients with pre-ACLF had the highest 3-month and 1-year LT-free mortality (61.6% and 70.9%, respectively), which was comparable to those with ACLF at enrollment (57.1% and 67.1%); the 251 (25.9%) patients with unstable decompensated cirrhosis had mortality rates of 22.4% and 32.1%, respectively; while the 507 (57.9%) patients with stable decompensated cirrhosis had the best outcomes (1-year mortality rate of 2.6%). Through Cox proportional hazard regression, specific precipitants, including hepatitis B flare with HBV reactivation, spontaneous hepatitis B flare with high viral load, superimposed infection on HBV, and bacterial infection, were identified to be significantly associated with ACLF occurrence in the derivation cohort. A model that incorporated precipitants, indicators of systemic inflammation and organ injuries reached a high C-index of 0.90 and 0.86 in derivation and validation cohorts, respectively. The optimal cut-off value (0.22) differentiated high-risk and low-risk patients, with a negative predictive value of 0.95.
Conclusions: Three distinct clinical courses of patients with AD are validated in the HBV-etiology population. The precipitants significantly impact on AD-ACLF transition. A model developed by the precipitant-systemic inflammation-organ injury framework could be a useful tool for predicting ACLF occurrence.
Clinical trial number: NCT02457637 and NCT03641872.
Lay summary: It was previously shown that patients with decompensated cirrhosis could be stratified into 3 groups based on their short-term clinical prognoses. Herein, we showed that this stratification applies to patients who develop cirrhosis as a result of hepatitis B virus infection. We also developed a precipitant-based model (i.e. a model that incorporated information about the exact cause of decompensation) that could predict the likelihood of these patients developing a very severe liver disease called acute-on-chronic liver failure (or ACLF).
Keywords: ACLF, acute-on-chronic liver failure; AD, acute decompensation; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CATCH-LIFE study, Chinese AcuTe-On-Chronic LIver FailurE Study; CLIF, Chronic Liver Failure; CLIF-C AD, CLIF consortium acute decompensation score; CRP, C-reactive protein; EASL, European Association for the Study of the Liver; HR, hazard ratio; INR, international normalized ratio; LT, liver transplantation; MELD, model for end-stage liver disease; NL, neutrophil-lymphocyte ratio; NPV, negative predictive value; OFs, organ failures; PPV, positive predictive value; PVT, portal vein thrombosis; SDC, stable decompensated cirrhosis; UDC, unstable decompensated cirrhosis; WBC, white blood cell; acute-on-chronic liver failure; acutely decompensated cirrhosis; hepatitis B virus; iMELD, integrated MELD; precipitants; prediction model.
© 2022 The Author(s).