Comparison of current diagnostic criteria for acute-on-chronic liver failure

Abstract

Background and aims: Currently, acute-on-chronic liver failure (ACLF) has been defined differently by Asia-Pacific Association for the Study of the Liver (APASL) and Chinese Medical Association (CMA) in the East, as well as EASL-Chronic Liver Failure (EASL-CLIF) Consortium in the West. This study aimed to compare current different diagnostic criteria for ACLF and to determine predictors of the progression into post-enrollment EASL-CLIF ACLF from ACLF at enrollment defined by APASL alone or by both APASL and CMA but not by EASL-CLIF Consortium.

Methods: We retrospectively analyzed clinical data from 394 eligible cirrhotic patients fulfilling at least APASL criteria for ACLF at enrollment. Patient survival was estimated by Kaplan-Meier analysis and subsequently compared by log-rank test. Independent predictors of disease progression were determined using univariate analysis and multivariate Cox regression analysis.

Results: The 90-day mortality rate was 13.1% in patients with ACLF at enrollment defined by APASL alone, 25.3% in patients with ACLF at enrollment defined by both APASL and CMA but not EASL-CLIF Consortium, and 59.3% in patients with ACLF at enrollment defined by EASL-CLIF Consortium in addition to APASL. Baseline Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) score, and the maximum rising rates of CLIF-SOFA score, Model for End-Stage Liver Disease-Sodium (MELD-Na) score and total bilirubin were independent predictors of progression into post-enrollment EASL-CLIF ACLF from ACLF at enrollment defined by APASL alone or by both APASL and CMA but not by EASL-CLIF Consortium.

Conclusion: Different diagnostic criteria for ACLF caused different patient prognosis. So, it is imperative to formulate a unifying diagnostic criteria for ACLF worldwide, thus attaining early identification and treatment, and eventual improvement in survival of ACLF patients. Baseline CLIF-SOFA score, and the maximum rising rates of CLIF-SOFA score, MELD-Na score and total bilirubin may early predict post-enrollment development of EASL-CLIF ACLF.

Fig 1. Flowchart of the study group selection process.

Abbreviations: ACLF, acute-on-chronic liver failure; APASL, Asia–Pacific Association for the Study of the Liver; CMA, Chinese Medical Association; EASL-CLIF, EASL-Chronic Liver Failure.

Fig 2. Comparison of survival among patients with ACLF at enrollment defined by different criteria.

Overall 394 eligible patients who qualified for at least APASL criteria for ACLF at enrollment were divided into 3 groups: patients satisfying APASL criteria alone for ACLF at enrollment (group A), patients satisfying both APASL and CMA criteria but not EASL-CLIF criteria for ACLF at enrollment (group B), and patients satisfying EASL-CLIF criteria in addition to APASL criteria for ACLF at enrollment (group C). In comparison with patients in group A and group B, the 90-day survival was significantly lower for patients in group C (log-rank test: P < 0.001). Besides, significantly lower survival was also observed for patients in group B, as compared to patients in group A (log-rank test: P < 0.05).

Fig 3. Comparison of survival between patients with and without progression to post-enrollment EASL-CLIF ACLF.

Patients with ACLF at enrollment defined by APASL criteria alone were classified into group A, while patients with ACLF at enrollment defined by both APASL and CMA criteria but not EASL-CLIF criteria were classified into group B. Among the entire 276 patients in groups A and B, patients with progression to post-enrollment EASL-CLIF ACLF had a significantly lower survival than those without (log-rank test: P < 0.001) (A). Among patients in either group A (B) or group B (C), significantly lower survival was also observed in patients with progression to post-enrollment EASL-CLIF ACLF than those without (log-rank test: P < 0.001). Abbreviations: ACLF, acute-on-chronic liver failure; EASL-CLIF, EASL-Chronic Liver Failure.

Fig 4. Mortality rate at 90 days according to the grade of ACLF defined by EASL-CLIF Consortium.

Among patients identified as EASL-CLIF ACLF either at enrollment or after enrollment, the 90-day mortality rate was 39.1% for grade 1, 54.1% for grade 2, 86.7% for grade 3, respectively. The 90-day mortality rate in patients without EASL-CLIF ACLF both at enrollment and after enrollment was 2.1%. Abbreviations: ACLF, acute-on-chronic liver failure.