The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

Abstract

Infections ACLF Death Different clinical courses of acutely decompensated cirrhosis Pre-ACLF Unstable decompensated cirrhosis Stable decompensated cirrhosis 0 90 180 270 360 Days Highlights Patients with acutely decompensated cirrhosis without ACLF develop 3 different clinical courses. Patients with pre-ACLF develop ACLF within 90 days and have high systemic inflammation and mortality. Patients with unstable decompensated cirrhosis suffer from complications of severe portal hypertension. Patients with stable decompensated cirrhosis have less frequent complications and lower 1-year mortality risk.

Systemic inflammation increases across distinct stages of advanced chronic liver disease and correlates with decompensation and mortality

“…5 Similarly, the PREDICT study suggests that the longitudinal development of SI after acute decompensation greatly determines the clinical course of ACLD. 23 Finally, our results suggest that IL-6 is a strong prognostic marker associated with considerable increased risk of death if not transplanted. Potentially, IL-6 levels might be used in future studies to identify individual dACLD patients who benefit most from therapeutic interventions targeting SI such as albumin administration 34 or NSBB intake.…”

“…Recently published data from the PREDICT study identified three different courses of acute decompensation, that showed different associations with portal hypertension and systemic inflammation as decisive pathomechanisms. 23 In the subgroup of patients presenting with first hepatic decompensation, levels of systemic inflammation were lowest in patients with gastrointestinal hemorrhage, as compared to patients with ascites or hepatic encephalopathy. These results are in line with our study, as we observed similar levels of systemic inflammation in patients in S3 (after variceal bleeding) as compared to compensated patients.…”

“…Therefore, the levels of SI in our study might not be similar to those observed in patients when sampled at the time of acute decompensation and/or pre-ACLF, as performed in the PREDICT study. 23 In cACLD patients, a small but steady increase of MELD across indicative of progressive hepatic dysfunction was noted. However, most pronounced increases were noted in severity of PH as evident by considerable increases in HVPG across the different sub-stages of cACLD.…”

Editorial: outcome prediction in patients with cirrhosis and acute‐on‐chronic liver failure—authors' reply

“…An ideal cohort may be the recently completed PREDICT multicentre study, which involved over 1000 patients with different courses of AD. While the accuracy of diverse established disease severity scores has been confirmed, the prognostic value of leucocyte ratios has not yet been reviewed 5 . Furthermore, the effect of confounders such as cancer, immunotherapy, renal failure, other (systemic) inflammatory diseases and non‐bacterial infection are also not yet fully known and these larger studies would allow such analysis.…”

Liver Transplantation in Acute‐on‐Chronic Liver Failure Is a Wise Longterm Investment

“…(2) Several reports have shown that patients with ACLF benefit from LT, (3)(4)(5) and the typically rapid progression of ACLF mandates a need for prompt evaluation for LT. (3,6) In pre-ACLF patients, as defined by the Predicting Acute-on-Chronic Liver Failure in Cirrhosis (PREDICT) Study, who will develop ACLF in 90 days, fast decision making, listing, and LT are also crucial. (5,7) An area of uncertainty is whether LT is justified in all ACLF patients with failure of more than 3 organs (grade 3b) and/or Chronic Liver Failure (CLIF)-C ACLF score ≥65, which predicts a lower likelihood of a favorable outcome with LT. (3,4) Although criteria to decline LT in ACLF grade 3b remain to be confirmed, some parameters have been proposed, such as high lactate levels, partial pressure of arterial oxygen (mmHg)/ fraction of inspired oxygen below 150 or 200, and pressor support with a high noradrenaline dose. (8) Patients with ACLF grade 3 have similar outcomes to other recipients requiring urgent LT. (6) The longterm outcomes of patients with ACLF after LT are addressed by Sundaram et al in the current issue.…”