Encephalopathy Connectomic Collapse Atlas (ECCA-HEP) | Hepatic Encephalopathy Biomarker Panel

SCF-ECCA-HEP-BIO-0002

Hepatic Encephalopathy Biomarker Panel

Liver–Gut–Brain Axis Connectomic Collapse Validation System

FDA-Aligned Endpoint Validation Framework for Precision Acupuncture Planning

Encephalopathy Connectomic Collapse Atlas (ECCA-HEP)

I. PURPOSE

The SCF Hepatic Encephalopathy Biomarker Panel is designed to:

Establish hepatic encephalopathy diagnosis and staging
Quantify liver–gut–brain connectomic collapse
Predict progression toward overt hepatic encephalopathy
Stratify personalized acupuncture neurocircuit selection
Monitor therapeutic response longitudinally
Forecast recurrence risk
Support FDA-aligned translational endpoint development
Enable precision neuromodulation planning

II. SCF HEPATIC ENCEPHALOPATHY BIOMARKER DOMAINS

Domain	Function
Hepatic Function	Quantifies liver reserve and injury
Hyperammonemia	Quantifies neurotoxic burden
Neuroaxonal Injury	Measures neuronal damage
Astrocytic Dysfunction	Measures ammonia-mediated astrocyte injury
BBB Integrity	Measures neurovascular disruption
Neuroimmune Activation	Measures inflammatory amplification
Gut Barrier Integrity	Measures gut-derived neurotoxicity
Mitochondrial Function	Measures bioenergetic collapse
Connectomic Function	Measures network synchronization
Autonomic Function	Measures neurovisceral regulation
Cognitive Function	Measures cortical performance
Recovery Prediction	Forecasts therapeutic responsiveness

III. HEPATIC FUNCTION PANEL

Tier 1 Liver Reserve Layer

Biomarker	Assay	Normal	Mild Risk	Moderate Risk	Severe Risk
Total Bilirubin	Clinical Chemistry	<1.2 mg/dL	1.2–2	2–5	>5
Direct Bilirubin	Clinical Chemistry	<0.3 mg/dL	0.3–1	1–3	>3
Albumin	Clinical Chemistry	>3.5 g/dL	3.0–3.5	2.5–3.0	<2.5
INR	Coagulation	<1.2	1.2–1.5	1.5–2.0	>2.0
ALT	Clinical Chemistry	<40 U/L	40–80	80–200	>200
AST	Clinical Chemistry	<40 U/L	40–80	80–200	>200

Endpoint

Hepatic Functional Reserve Index (HFRI)

IV. HYPERAMMONEMIA PANEL

Tier 2 Neurotoxic Burden Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
Plasma Ammonia	Enzymatic Assay	<35 µmol/L	35–60	60–100	>100
Venous Ammonia	Clinical Chemistry	<50 µmol/L	50–80	80–120	>120
Glutamine	LC-MS/MS	Reference	Elevated	High	Very High
Glutamate/Glutamine Ratio	LC-MS/MS	Normal	Mild Shift	Moderate Shift	Severe Shift

Endpoint

Neurotoxic Ammonia Burden Score (NABS)

V. ASTROCYTE DYSFUNCTION PANEL

Tier 3 Astroglial Collapse Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
GFAP	Simoa	<120 pg/mL	120–250	250–500	>500
S100B	Immunoassay	<0.1 ng/mL	0.1–0.2	0.2–0.5	>0.5
Myo-Inositol (MRS)	MRI Spectroscopy	Normal	↓10%	↓25%	↓50%
Glx Peak (MRS)	MRI Spectroscopy	Normal	↑10%	↑25%	↑50%

Endpoint

Astrocytic Swelling Severity Score (ASSS)

VI. NEUROAXONAL INJURY PANEL

Tier 4 Connectomic Injury Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
NfL	Simoa	<10 pg/mL	10–20	20–50	>50
Total Tau	Simoa	<2 pg/mL	2–4	4–8	>8
NSE	CLIA	<12 ng/mL	12–18	18–25	>25
UCH-L1	ELISA	<100 pg/mL	100–200	200–400	>400

Endpoint

Neuroaxonal Injury Index (NAII)

VII. BBB INTEGRITY PANEL

Tier 5 Neurovascular Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
Albumin Quotient	CSF/Serum	<6.5	6.5–8	8–12	>12
S100B	Immunoassay	<0.1	0.1–0.2	0.2–0.5	>0.5
MMP-9	ELISA	<150 ng/mL	150–250	250–400	>400
VEGF	ELISA	Normal	Elevated	High	Very High

Endpoint

BBB Permeability Index (BBPI)

VIII. NEUROIMMUNE PANEL

Tier 6 Inflammatory Amplification Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
IL-6	Multiplex	<2 pg/mL	2–10	10–50	>50
TNF-α	Multiplex	<5 pg/mL	5–15	15–30	>30
IL-1β	Multiplex	<1 pg/mL	1–5	5–15	>15
hsCRP	Immunoassay	<1 mg/L	1–3	3–10	>10

Endpoint

Neuroimmune Amplification Score (NIAS)

IX. GUT–LIVER AXIS PANEL

Tier 7 Gut-Derived Neurotoxicity Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
LPS	ELISA	Low	Elevated	High	Very High
LBP	ELISA	Normal	Elevated	High	Very High
Zonulin	ELISA	Normal	Elevated	High	Very High
Calprotectin	ELISA	<50 µg/g	50–150	150–300	>300
Indoxyl Sulfate	LC-MS/MS	Normal	Elevated	High	Very High

Endpoint

Gut–Brain Toxicity Index (GBTI)

X. MITOCHONDRIAL COLLAPSE PANEL

Tier 8 Bioenergetic Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
Lactate	Clinical Chemistry	0.5–2.0 mmol/L	2–3	3–5	>5
Pyruvate	LC-MS	Normal	Elevated	High	Very High
Lactate/Pyruvate Ratio	LC-MS	<20	20–30	30–40	>40
ATP Production Rate	Seahorse	Normal	↓10%	↓25%	↓50%

Endpoint

Bioenergetic Failure Index (BFI)

XI. CONNECTOMIC FUNCTION PANEL

Tier 9 Connectomic Collapse Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
EEG Delta Power	qEEG	Normal	+20%	+50%	+100%
EEG Theta Excess	qEEG	Normal	Mild	Moderate	Severe
Alpha Connectivity	qEEG	Normal	↓10%	↓25%	↓50%
rs-fMRI Connectivity	MRI	Normal	↓10%	↓25%	↓50%
DTI Fractional Anisotropy	MRI-DTI	Normal	↓5%	↓10%	↓20%

Endpoint

Connectomic Collapse Index (CCI)

XII. AUTONOMIC FUNCTION PANEL

Tier 10 Neurovisceral Layer

Biomarker	Assay	Normal	Mild	Moderate	Severe
HRV SDNN	ECG	>100 ms	80–100	50–80	<50
RMSSD	ECG	>30 ms	20–30	10–20	<10
LF/HF Ratio	HRV	1–2	2–3	3–5	>5
Orthostatic HR Increase	Tilt Table	<20 bpm	20–30	30–40	>40

Endpoint

Autonomic Collapse Index (ACI)

XIII. COGNITIVE ENDPOINT PANEL

Tier 11 Functional Outcome Layer

Endpoint	Normal	Mild	Moderate	Severe
MoCA	≥26	22–25	16–21	<16
PHES Score	Normal	Mild Impairment	Moderate	Severe
Trail Making Test-B	<75 sec	75–120	120–180	>180
Critical Flicker Frequency	>39 Hz	35–39	30–35	<30

Endpoint

Hepatic Connectomic Performance Score (HCPS)

XIV. SCF ACUPUNCTURE RESPONSE FORECAST PANEL

Personalized Neurocircuit Selection Layer

Biomarker Pattern	Predicted Dysfunction	Primary Acupuncture Network
Hyperammonemia + Elevated Glutamine	Astrocytic swelling	GV20 + ST36 + BL18
Elevated GFAP + S100B	Astroglial collapse	GV20 + Sishencong + PC6
Elevated LPS + Zonulin	Gut-brain toxicity	ST25 + CV12 + BL20
Elevated IL-6 + TNF-α	Neuroimmune amplification	ST36 + LI11
HRV Suppression	Dysautonomia	PC6 + HT7 + CV17
Reduced rs-fMRI Connectivity	Connectomic collapse	GV20 + GV24 + Sishencong
Elevated Lactate/Pyruvate Ratio	Bioenergetic failure	KI3 + SP6 + ST36
Elevated Bilirubin + INR	Hepatic reserve failure	BL18 + LV3 + ST36

XV. SCF PRECISION FORECASTING MODEL

Low-Risk Recovery

Criteria:

Ammonia <60 µmol/L
GFAP <250 pg/mL
HRV preserved
MoCA >24
PHES mildly impaired or normal

Predicted Response:

High probability of favorable neuromodulation response.

Intermediate Risk

Criteria:

Ammonia 60–100 µmol/L
GFAP 250–500 pg/mL
Moderate EEG slowing
MoCA 18–24

Predicted Response:

Moderate response requiring prolonged intervention and liver-directed management.

High-Risk Progression

Criteria:

Ammonia >100 µmol/L
GFAP >500 pg/mL
Severe EEG slowing
Major rs-fMRI connectivity loss
MoCA <18

Predicted Response:

High risk of progression to overt hepatic encephalopathy; limited benefit from neuromodulation alone.

XVI. COMPOSITE SCF HEPATIC ENCEPHALOPATHY SCORE (SCF-HES)

Weighted Domains

Domain	Weight
Hepatic Function	15%
Hyperammonemia	15%
Astrocyte Dysfunction	15%
Neuroaxonal Injury	10%
BBB Integrity	10%
Neuroimmune Activity	10%
Gut–Liver Axis Dysfunction	10%
Connectomics	10%
Autonomics	3%
Cognition	2%

Interpretation

Score	Classification
<20	Stable
20–40	Minimal Hepatic Connectomic Dysfunction
40–60	Moderate Connectomic Collapse
60–80	Severe Hepatic Encephalopathy
>80	Critical Liver–Gut–Brain Failure

XVII. PRIMARY FDA-ALIGNED CLINICAL ENDPOINTS

Diagnostic Endpoints

Plasma Ammonia
PHES
Critical Flicker Frequency
MoCA
EEG Slowing Index

Predictive Endpoints

NfL
GFAP
rs-fMRI Connectivity
HRV SDNN
LPS/Zonulin Composite

Therapeutic Response Endpoints

Reduction in Ammonia
Improvement in PHES
Improvement in MoCA
Restoration of HRV
Improvement in Connectomic Collapse Index

NEXT PANEL IN SEQUENCE

SCF-ECCA-PV-BIO-0003

Post-Viral / Long COVID Encephalopathy Biomarker Panel

(Viral Neuroimmune Connectomic Collapse Validation System)

MASTER REGISTRY INDEX

SCF-ECCA-HEP-BIO-0002 — Hepatic Encephalopathy Biomarker Panel
SCF-ECCA-HEP-ACU-0002 — Hepatic Encephalopathy Acupoint Neuro-Circuit Mapping Atlas
SCF-ECCA-0001 — Encephalopathy Connectomic Collapse Atlas
SCF-BIOMARKER-ENDPOINTS-0001 — SCF Biomarker Endpoint Validation Framework
SCF-PATH-PROT-0001 — SCF Pathophysiology Protocol
SCF-ACU-NEURO-ATLAS-0001 — SCF Neural Mapping Schema