Overview
Gate 0 · ACLF / Acute Decompensation Programme
Gate 0 · Active
Layer 1 · Clinical Phenotypes
7
Organ failure types
↑ 2 added
Layer 2 · Sys. Mechanisms
6
Pathophysiology
↑ 1 added
Layer 3 · Bio. Pathways
8
Signaling cascades
↑ 3 added
Layer 4 · Molecules
9
Mechanistic + biomarkers
↑ 2 added
Top Causal Hypotheses · Ranked by Evidence Confidence
01
IL-6/JAK-STAT hyperactivation drives early ACLF-3 progression via innate immune cascade
EF CLIF cytokinomics · n=282 ACLF · 3 independent validations · Trebicka J et al. J Hepatol 2021
CausalARS Candidate
87%
Strong
02
Immune paralysis (IL-10/PD-1 axis) dominant late-stage ACLF-2/3 transition driver
EF CLIF transcriptomics · n=1,400 · Bernsmeier C et al. J Hepatol 2015 · Literature n=31 papers
CausalARS Candidate
74%
Moderate
03
Immunothrombosis (TF-Thrombin/NLRP3) mediates ACLF-2 coagulation + AKI co-occurrence
EF CLIF metabolomics + cytokinomics · Bernal W et al. J Hepatol 2021 · 47 literature papers
CausalARS Candidate
61%
Moderate
Intelligence Alerts
EASL 2026: CANONIC-2 preliminary data — ACLF biomarker stratification by aetiology
2 hours ago · High relevance · Layer 1+2 impact
Protagonist Ph.2 initiates in ACLF — IL-6R antagonist arm added per ClinicalTrials.gov NCT0567xxxx
1 day ago · Competitive · Asset Evaluator impact
Nature Medicine: Single-cell atlas of ACLF liver — novel myeloid subpopulations (Zhang Y et al.)
3 days ago · High relevance · Layer 2+4 impact
FDA guidance update: Biomarker qualification for acute liver failure endpoints — affects ARS design
1 week ago · Regulatory · ARS Candidates impact
Data Source Status · Slide 15 datasets
EF CLIF Multi-omics
~4,700 pts
Komodo Health RWD
1.5M+ pts
Public Omics (GEO/ArrayExpress/PRIDE)
47 studies
External Phase 2b Trial
130+ pts
Sepsis Biobank (ARISE trial)
Partnership pending
APASL Asian Cohort (HBV-ACLF)
Agreement active
Conditioning PoS · All 5 Dimensions · Gate 0 Progress (Slide 6)
Translational Biological Actionability
78%On Track
Translational Measurability (ARS)
64%In Progress
Translational Coherence
59%In Progress
Patient Stratification Success
71%On Track
Strategic Exploitability
68%On Track