A total of 4,432 consecutive, prospectively registered patients who underwent LT from 2010 to 2020 were enrolled after approval from the Institutional Review Boards of Asan Medical Center (no. S2022-0688). Of these patients, according to the STROBE (strengthening the reporting of observational studies in epidemiology) Statement with effort to address potential sources of bias, we excluded patients with less than 18 years old, re-transplantation, toxic or fulminant hepatitis, and incomplete data (Fig. 1). Out of 3,764 end-stage liver disease who underwent LT, final 921 ACLF patients according to definition from chronic liver failure consortium ACLF score (CLIF-C ACLFs) was selected.

Patient demographics, medical history, model for end-stage liver disease score (MELDs), and laboratory and intraoperative variables were automatically obtained using a fully computerized data extraction software (ABLE). Mortality data were obtained from patients’ electronic medical records and the updated record from the institution’s LT registry.

Briefly, the CLIF-C ACLFs were defined as follows; Liver failure: bilirubin level of > 12 mg/dl, kidney failure: creatinine > 2.0 mg/dl or renal replacement, brain failure: hepatic encephalopathy grade by West-Haven, 3-4, coagulation failure: international normalized ratio ≥ 2.5, circulatory failure: use of vasopressor, respiratory failure: PaO₂/FiO₂ ≤ 200; SpO₂/FiO₂ ≤ 214; or on ventilator treatment [10].

The grade of ACLF was based on the CLIF-C organ failure (CLIF-C OF) criteria including 6 failing organs (liver, kidney, brain, coagulation, circulation, and respiration). Briefly, a) presence of at least renal failure, b) any other single organ failure if associated with renal dysfunction (serum creatinine 1.5-1.9 mg/dl) and/or grade I-II hepatic encephalopathy (ACLF-grade 1). Patients with two failing organs were graded as ACLF-grade 2, while those with three or more failing organs were graded as ACLF-grade 3 [8,11].

CAD was diagnosed by cardiologists based on the pretransplant history with imaging study and angiography. CAD was considered “appropriately treated” when patients with CAD have previous history of coronary artery bypass graft or percutaneous intervention and old myocardial infarction with antianginal medications.

The primary outcome was Kaplan-Meier cumulative all-cause mortality at 5 years since the date of LT. Mortality data were collected from the medical record database and the institution’s LT registry, which is regularly updated by the Organ Transplantation Center.

Data were expressed as mean with standard deviation or median with interquartile range (IQR) for continuous variables, and numbers and percentages for categorical variables. In univariate statistical comparisons, the chi-square test or Fisher’s exact test was used for categorical variables, Student’s t-test and Mann-Whitney test for continuous variables, as appropriate. The Kaplan-Meier survival curve was used to depict the risk of all-cause mortality up to 5 years follow-up period. The proportional hazard assumption was tested by analysis of Schoenfeld residuals and log-rank test was performed for the comparison. When the assumption was violated, Gehan-Breslow-Wilcoxon test was used. To evaluate the relationship between clinical, biochemical parameters, liver disease severity and mortality events, a Cox proportional multiple regression model was built and obtained adjusted hazard ratios (HR) for 5-year mortality. Covariates included for Cox analysis were age, sex, body mass index, diabetes, hypertension, MELD score, intraoperative red blood cell transfusion, and post-reperfusion syndrome. Statistical analyses were conducted in R (Version 4.1.2, R Foundation for Statistical Computing, Austria), with packages of ‘moonBook’ [12], ‘autoReg’ [13], “survminer” [14] “survival” [15] and a 2-sided significance level of 0.05.

CAD patients (n = 58, 6.3%) showed increased age, and higher prevalence of history of previous cardiovascular disease including stroke and diabetes, but pretransplant MELD score and intraoperative transfusion amount and postreperfusion syndrome were similar (Table 1).

In patients with CAD (6.3%, 58/921), the Kaplan-Meier cumulative mortality rate at 5 years was numerically higher but was not statistically significant when compared with those without CAD (32.9% vs. 23.5%, log-rank, P = 0.25, Fig. 2). In subgroup analysis, there were comparable risks of cumulative mortality at 5 years across the stratification of ACLF grade 1, 2, and 3 (Gehan-Breslow-Wilcoxon P = 0.19, log-rank P = 0.72, and log-rank P = 0.999, respectively, Fig. 3).

In multivariable Cox proportional HR analysis, CAD did not remain as an important determinant for 5-year survival, as expected in the univariate analysis (Fig. 4).