Improved prediction of mortality by combinations of inflammatory markers and standard clinical scores in patients with acute-on-chronic liver failure and acute decompensation

Background and Aim Acute-on-chronic liver failure (ACLF) is a sinister prognosis, and there is a need for accurate biomarkers and scoring systems to better characterize ACLF patients and predict prognosis. Systemic inflammation and renal failure are hallmarks in ACLF disease development and progression. We hypothesized that the combination of specific inflammatory markers in combination with clinical scores are better predictors of survival than the originally developed CLIF-C acute decompensation (AD) and CLIF-C ACLF scores. Methods We reevaluated all previously measured inflammatory markers in 522 patients from the CANONIC study, 342withoutand 180withACLF. We used the Harrell's C-index to determine the best marker alone or in combination with the original scores and calculated new scores for prediction of mortality in the original CANONIC cohort. Results The best markers to predict 90-day mortality in patientswithoutACLF were the plasma macrophage activation markers soluble (s)CD163 and mannose receptor (sMR). Urinary neutrophil gelatinase associated lipocalin (UNGAL) and sCD163 were predictors for 28-day mortality in patientswithACLF. The newly developed CLIF-C AD + sMR score in patientswithoutACLF improved 90-day mortality prediction compared with the original CLIF-C AD score (C-index 0.82 [0.78-0.86]vs0.74 [0.70-0.78,P = 0.004]). Further, the new CLIF-C ACLF + sCD163 + UNGAL improved the original CLIF-C ACLF score for 28-day mortality (0.85 [0.79-0.91]vs0.75 [0.70-0.80],P = 0.039). Conclusions The capability of these inflammatory markers to improve the original prognostic scores in cirrhosis patientswithoutandwithACLF points to a key role of macrophage activation and inflammation in the development and progression of AD and ACLF.