SCF-HEP-MNSS-TEMP-0007
SCF Disease Progression Timeline Mapping
Hepatic Encephalopathy (HE)
Therapeutic Temporal Windows Mapped to SCF Multi-Neurosystems Shock States (MNSS)
Integrated Neuroimmune, Neurocardiac, Neurovascular, Neurometabolic, and Neuroendocrine Shock-State Architecture
Pre-Encephalopathy → Overt Hepatic Encephalopathy → Post-Encephalopathy Reconstruction
I. SCF HEPATIC ENCEPHALOPATHY MASTER PATHOGENESIS CASCADE
Etiopathogenic Core
Chronic Liver Disease / Acute Liver Failure
↓
Portal Hypertension
↓
Hepatic Detoxification Failure
↓
Hyperammonemia
↓
Gut-Liver Axis Dysbiosis
↓
Systemic Inflammation
↓
Astrocytic Glutamine Overload
↓
Astrocyte Swelling
↓
BBB Dysfunction
↓
Neuroimmune Activation
↓
Neurometabolic Collapse
↓
Neuroendocrine Dysregulation
↓
Neurocardiac Autonomic Dysfunction
↓
Connectomic Collapse
↓
Overt Hepatic Encephalopathy
↓
Post-Hepatic Neurocognitive Syndrome
II. MASTER TEMPORAL PROGRESSION MATRIX
SCF Phase | Temporal Window | Dominant Shock State | Clinical Stage | Reversibility |
MNSS-0 | Months–Years | Compensated State | Cirrhosis without HE | Very High |
MNSS-IA | Weeks–Months | Neurometabolic Priming | Subclinical HE risk | Very High |
MNSS-IB | Days–Weeks | Neuroimmune-Astrocytic Priming | Minimal HE | Very High |
MNSS-II | Days Before Overt HE | Neuroglial-Neurometabolic Shock | Minimal/Covert HE | High |
MNSS-IIIA | Hours–Days | Early Overt HE | West Haven I–II | High |
MNSS-IIIB | Days–Weeks | Established HE | West Haven II–III | Moderate |
MNSS-IV | Hours–Days | Global Multi-Neurosystems Shock | West Haven III–IV | Limited |
MNSS-R1 | Days–Weeks | Shock Resolution | Recovery Initiation | High |
MNSS-R2 | Weeks–Months | Connectomic Reconstruction | Cognitive Recovery | Moderate–High |
MNSS-R3 | Months–Years | Neuroadaptive Compensation | Post-HE Syndrome | Variable |
III. PRE-ENCEPHALOPATHY WINDOW 1
MNSS-IA — HYPERAMMONEMIC PRIMING
Temporal Window
Weeks to Months Before Clinical HE
Dominant SCF Shock States
- Neurometabolic Shock (NMS-1)
- Neuroendocrine Shock (NES-1)
SCF Biomarker Panel
Domain | Biomarker | Baseline | Alert Threshold |
Neurometabolic | Plasma Ammonia | <50 µmol/L | >60 µmol/L |
Neurometabolic | Glutamine | Normal | Elevated |
Neurometabolic | Lactate/Pyruvate Ratio | <20 | >25 |
Neurometabolic | cf-mtDNA | Low | Elevated |
Neuroendocrine | Cortisol Rhythm | Normal | Flattening |
Neuroendocrine | IGF-1 | Normal | ↓20% |
Neuroendocrine | DHEA-S | Normal | ↓15% |
Neurocardiac | SDNN | >100 ms | <90 ms |
Clinical Manifestations
- Sleep disturbance
- Mild fatigue
- Reduced mental endurance
- Subclinical executive dysfunction
Therapeutic Objective
Prevent astrocytic glutamine accumulation.
IV. PRE-ENCEPHALOPATHY WINDOW 2
MNSS-IB — NEUROIMMUNE-ASTROCYTIC PRIMING
Temporal Window
Days to Weeks Before Minimal HE
Dominant Shock States
- Neuroimmune Shock (NIS-1)
- Neurovascular Shock (NVS-1)
- Neuroglial Shock (NGS-1)
SCF Biomarker Panel
Domain | Biomarker | Alert Threshold |
Neuroimmune | IL-6 | >10 pg/mL |
Neuroimmune | TNF-α | >10 pg/mL |
Neuroimmune | HMGB1 | >5 ng/mL |
Neuroimmune | IL-1β | Elevated |
Neuroglial | GFAP | >120 pg/mL |
Neuroglial | YKL-40 | >80 ng/mL |
Neuroglial | S100B | >0.1 ng/mL |
Neurovascular | MMP-9 | >200 ng/mL |
Neurovascular | Albumin Quotient | Rising |
Neurovascular | VEGF | Elevated |
Clinical Manifestations
- Brain fog
- Slowed psychomotor speed
- Reduced concentration
- Early sleep-wake inversion
Therapeutic Objective
Prevent progression to covert hepatic encephalopathy.
V. PRE-OVERT HEPATIC ENCEPHALOPATHY
MNSS-II — ASTROCYTIC-NEUROMETABOLIC SHOCK
Temporal Window
Days Before Overt HE
Dominant Shock States
- Neuroglial Shock (NGS-2)
- Neurometabolic Shock (NMS-2)
- Neurovascular Shock (NVS-2)
SCF Biomarker Panel
Domain | Biomarker | Threshold |
Neurometabolic | Ammonia | >80 µmol/L |
Neurometabolic | Lactate | >2 mmol/L |
Neurometabolic | ATP Production | ↓20–30% |
Neuroglial | GFAP | >180 pg/mL |
Neuroglial | S100B | >0.15 ng/mL |
Neuroglial | YKL-40 | >120 ng/mL |
Neurovascular | MMP-9 | >250 ng/mL |
Neurovascular | Albumin Quotient | Elevated |
Connectomic | qEEG Connectivity | >10% decline |
Clinical Manifestations
Minimal Hepatic Encephalopathy
- Impaired attention
- Reduced reaction time
- Executive dysfunction
- Driving impairment
Therapeutic Objective
Prevent transition to West Haven Grade I HE.
VI. EARLY OVERT HEPATIC ENCEPHALOPATHY
MNSS-IIIA
Temporal Window
Hours–Days After Symptom Recognition
Dominant Shock States
- Neuroimmune Shock (NIS-2)
- Neuroglial Shock (NGS-3)
- Neurocardiac Shock (NCS-1)
SCF Biomarker Panel
Domain | Biomarker | Threshold |
Neuroimmune | IL-6 | >20 pg/mL |
Neuroimmune | TNF-α | >15 pg/mL |
Neuroimmune | HMGB1 | Elevated |
Neuroglial | GFAP | >250 pg/mL |
Neuroglial | S100B | >0.20 ng/mL |
Neurocardiac | SDNN | <80 ms |
Neurocardiac | RMSSD | <20 ms |
Connectomic | EEG Theta | Increased |
Connectomic | EEG Delta | Increased |
Clinical Manifestations
West Haven Grade I–II
- Confusion
- Disorientation
- Personality change
- Impaired concentration
Therapeutic Objective
Preserve thalamocortical integrity.
VII. ESTABLISHED HEPATIC ENCEPHALOPATHY
MNSS-IIIB
Temporal Window
Days–Weeks
Dominant Shock States
- Neuroaxonal Shock (NAS-1)
- Neurocardiac Shock (NCS-2)
- Neurometabolic Shock (NMS-3)
SCF Biomarker Panel
Domain | Biomarker | Threshold |
Neuroaxonal | NfL | >20 pg/mL |
Neuroaxonal | UCH-L1 | Elevated |
Neuroaxonal | NSE | Elevated |
Neuroaxonal | Tau | Elevated |
Neurocardiac | SDNN | <80 ms |
Neurocardiac | QTc | Prolonged |
Neurometabolic | Ammonia | >120 µmol/L |
Neurometabolic | Lactate | >3 mmol/L |
Neurometabolic | ATP Production | ↓40% |
Clinical Manifestations
West Haven Grade II–III
- Marked confusion
- Asterixis
- Executive collapse
- Dysautonomia
Therapeutic Objective
Prevent cerebral edema and irreversible axonal injury.
VIII. ACUTE MULTI-NEUROSYSTEMS SHOCK
MNSS-IV
Temporal Window
Hours–Days
Dominant Shock States
- Neuroimmune Shock (NIS-4)
- Neurocardiac Shock (NCS-3)
- Neurovascular Shock (NVS-3)
- Neurometabolic Shock (NMS-4)
- Neuroendocrine Shock (NES-3)
SCF Peak Biomarker Panel
Shock Domain | Peak Biomarkers |
Neuroimmune | IL-6, TNF-α, HMGB1 |
Neurocardiac | SDNN <50 ms, RMSSD severely reduced, Troponin ↑ |
Neurovascular | MMP-9 peak, S100B peak, Albumin Quotient peak |
Neurometabolic | Ammonia >150–200 µmol/L, Lactate >4 mmol/L, cf-mtDNA peak |
Neuroendocrine | Cortisol dysregulation, ACTH dysregulation, IGF-1 suppression |
Neuroglial | GFAP peak, YKL-40 peak |
Neuroaxonal | NfL peak, UCH-L1 peak, Tau peak |
Clinical Manifestations
West Haven Grade III–IV
- Stupor
- Coma
- Respiratory compromise
- Cerebral edema risk
- Multi-organ dysfunction
Therapeutic Objective
Life preservation and prevention of permanent neurologic injury.
IX. POST-ENCEPHALOPATHY RECOVERY WINDOW
MNSS-R1 — SHOCK RESOLUTION
Temporal Window
Days–Weeks
Recovery Biomarker Panel
Domain | Biomarker Trend |
Neuroimmune | IL-6 ↓, TNF-α ↓, HMGB1 ↓ |
Neurocardiac | SDNN ↑, RMSSD ↑ |
Neurovascular | MMP-9 ↓ |
Neurometabolic | Ammonia ↓, Lactate ↓ |
Neuroglial | GFAP ↓ |
Therapeutic Objective
Accelerate neurocognitive recovery and reduce recurrence risk.
X. CONNECTOMIC RECONSTRUCTION WINDOW
MNSS-R2
Temporal Window
Weeks–Months
Reconstruction Biomarker Panel
Domain | Desired Trend |
Neuroglial | GFAP ↓ |
Neuroaxonal | NfL ↓ |
Connectomic | qEEG Connectivity ↑ |
Connectomic | DTI Fractional Anisotropy ↑ |
Neurocardiac | HRV SDNN ↑ |
Neuroendocrine | Cortisol Rhythm Restored |
Neuroendocrine | IGF-1 Improving |
Therapeutic Objective
Restore executive, attentional, and thalamocortical network function.
XI. POST-HEPATIC ENCEPHALOPATHY SYNDROME
MNSS-R3
Temporal Window
Months–Years
Persistent Risk Biomarker Panel
Shock Domain | Persistent Biomarkers |
Neuroimmune | IL-6, HMGB1, YKL-40 |
Neurocardiac | SDNN suppression, LF/HF elevation |
Neurovascular | MMP-9 elevation |
Neurometabolic | Residual mitochondrial dysfunction |
Neuroendocrine | Cortisol rhythm loss, low IGF-1 |
Neuroglial | GFAP elevation |
Neuroaxonal | NfL, Tau |
Connectomic | Persistent qEEG dysconnectivity |
Clinical Manifestations
- Residual cognitive impairment
- Executive dysfunction
- Sleep disorders
- Chronic fatigue
- Increased recurrence susceptibility
XII. MASTER SCF HEPATIC ENCEPHALOPATHY BIOMARKER MATRIX
SCF Phase | Neuroimmune Shock | Neurocardiac Shock | Neurovascular Shock | Neurometabolic Shock | Neuroendocrine Shock |
MNSS-IA | IL-6 | SDNN ↓ | MMP-9 ↑ | Ammonia ↑ | Cortisol ↑ |
MNSS-IB | HMGB1 ↑ | LF/HF ↑ | Albumin Quotient ↑ | Glutamine ↑ | DHEA-S ↓ |
MNSS-II | IL-6 ↑↑ | HRV ↓↓ | S100B ↑ | Lactate ↑ | Circadian disruption |
MNSS-IIIA | Cytokine surge | Dysautonomia | BBB dysfunction | ATP loss | HPA activation |
MNSS-IIIB | Persistent inflammation | QTc prolongation | Endothelial dysfunction | Hyperammonemia | IGF-1 suppression |
MNSS-IV | Peak cytokines | Severe autonomic collapse | Peak BBB injury | Peak ammonia/lactate | HPA collapse |
MNSS-R1 | Resolution | HRV recovery | BBB repair | Ammonia normalization | Endocrine recovery |
MNSS-R2 | Low inflammation | SDNN ↑ | Vascular repair | ATP restoration | Circadian restoration |
MNSS-R3 | Residual inflammation | Persistent dysautonomia | Residual dysfunction | Chronic bioenergetic deficit | Neuroendocrine maladaptation |
XIII. HIGHEST-VALUE THERAPEUTIC WINDOWS
Rank | Window | SCF Phase | Reversibility | Therapeutic Goal |
1 | Hyperammonemic Priming | MNSS-IA | Very High | Prevent astrocytic swelling |
2 | Neuroimmune-Astrocytic Priming | MNSS-IB | Very High | Prevent covert HE |
3 | Astrocytic-Neurometabolic Shock | MNSS-II | High | Prevent overt HE |
4 | Early Overt HE | MNSS-IIIA | High | Preserve connectomic integrity |
5 | Established HE | MNSS-IIIB | Moderate | Prevent axonal injury |
6 | Global Shock | MNSS-IV | Limited | Preserve life and neurologic function |
7 | Connectomic Reconstruction | MNSS-R2 | Moderate–High | Restore cognitive performance |
XIV. EARLIEST PREDICTIVE SCF BIOMARKER PANEL FOR HEPATIC ENCEPHALOPATHY
Tier 1 — Neurometabolic Predictors
- Plasma Ammonia
- Glutamine
- Lactate/Pyruvate Ratio
- cf-mtDNA
Tier 2 — Neuroimmune Predictors
- IL-6
- TNF-α
- HMGB1
Tier 3 — Neuroglial Predictors
- GFAP
- YKL-40
- S100B
Tier 4 — Neurocardiac Predictors
- HRV SDNN
- RMSSD
- LF/HF Ratio
Tier 5 — Neuroendocrine Predictors
- Cortisol Circadian Rhythm
- IGF-1
- DHEA-S
These biomarkers collectively define the highest-value intervention period preceding Minimal Hepatic Encephalopathy and overt West Haven Grade I–IV disease.
MASTER REGISTRY INDEX
- SCF-HEP-MNSS-TEMP-0007 — Hepatic Encephalopathy Disease Progression Timeline Mapping
- SCF-ECCA-HEP-0001 — Hepatic Encephalopathy Module
- SCF-ECCA-HEP-BIO-0002 — Hepatic Encephalopathy Biomarker Panel
- SCF-MNSS-0001 — Multi-Neurosystems Shock State Framework
- SCF-CONNECTOMIC-RECONSTRUCTION-0001 — Neuroimmune Connectomic Reconstruction Framework
- SCF-BIOMARKER-ENDPOINTS-0001 — Biomarker Endpoint Validation Framework
- SCF-PATH-PROT-0001 — SCF Pathophysiology Protocol
- SCF-ACU-NEURO-ATLAS-0001 — SCF Neural Mapping Schema