TOBINintel · Condition

Fatty Liver Disease (MASLD)

Metabolic dysfunction-associated steatotic liver disease (formerly NAFLD) is fat in the liver with at least one cardiometabolic risk factor. It affects about one in three adults; fibrosis stage, estimated with the FIB-4 score, drives outcomes.

Key points

Gut-derived endotoxin and microbial ethanol production are studied mechanisms; microbiome therapies remain investigational.
Test to discuss: ALT, AST, GGT
Test to discuss: FIB-4 = (age × AST) ÷ (platelets × √ALT)
Test to discuss: Liver ultrasound or elastography (FibroScan)
Test to discuss: HbA1c, fasting glucose, insulin, lipids
Test to discuss: Alcohol intake history
Weight loss of 7–10% where overweight
Limit sugar-sweetened beverages
Minimize alcohol
150+ minutes of activity weekly

Root-cause chain

Insulin resistance → Hepatic fat accumulationA

B · Established causal · Hyperinsulinemia drives de-novo lipogenesis and adipose free-fatty-acid flux to the liver.

Fructose and excess energy intake → Liver fatA

N · Randomized evidence · Controlled feeding trials show added fructose raises intrahepatic fat.

Lipotoxicity and oxidative stress → Steatohepatitis and fibrosisB

O · Observational association · Mitochondrial overload produces reactive oxygen species that activate stellate cells.

Endocrine-active and hepatotoxic chemicals → SteatosisD

T · Exposure signal · PFAS and some solvents associate with ALT and steatosis in NHANES; causation in humans is unproven.

Protocols by lane

Evidence grade + regulatory status

Conventional: Resmetirom for steatohepatitis with F2–F3 fibrosis; GLP-1 RA for comorbid obesity/diabetesA

Resmetirom FDA-approved 2024 (MAESTRO-NASH); GLP-1 RAs reduce liver fat.

Status: FDA-approved · Cautions: Specialist assessment; drug interactions with statins for resmetirom.

Functional: Structured 7–10% weight-loss programA

Weight loss ≥ 10% resolves steatohepatitis in most patients (Vilar-Gomez 2015).

Status: Lifestyle · Cautions: Rapid loss can precipitate gallstones.

Integrative: Aerobic plus resistance exerciseA

Reduces liver fat independent of weight loss.

Status: Lifestyle · Cautions: Cardiac clearance where indicated.

Orthomolecular: Vitamin E 800 IU/day in biopsy-proven non-diabetic steatohepatitisB

Improved histology in the PIVENS trial.

Status: Supplement · Cautions: Possible prostate-cancer and bleeding risk; avoid with anticoagulants.

Traditional: Mediterranean dietary pattern; coffee intakeB

Lower liver fat in trials; coffee associates with lower fibrosis.

Status: Lifestyle · Cautions: Adapt to sensitivity and sleep.

Energy / Physical: No energy modality has evidence for MASLDE

Listed for completeness only.

Status: Investigational · Cautions: Must not be presented as a treatment.

Monitoring

FIB-4 every 1–2 years (low risk < 1.3, high risk > 2.67)
Weight and waist trend
Liver enzymes every 6–12 months
TOBIN score change over time

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iDetection of an exposure does not establish that it caused a disease. This platform separates exposure, association, plausible mechanism, clinical evidence and demonstrated causation.