Viral Hepatitis

Drug-Induced Liver Injury

Primary Hepatocyte Injury

Massive Hepatocellular Necrosis

Release of DAMPs (DNA, histones, HMGB-1) and/dr Viral

Activation of Innate Immunity (Macrophages, neutrophils, dendritic & NK cells)

Production of ROS + Pro-inflammatory Cytokines (TNF-α, IL-1β, IL-6, IL-17 and others)

Systemic Inflammatory Response

Neutrophil infiltration into liver More ROS + Proteases Worsening hepatocyte damage

Progression to Multi-Organ Failure

Lrpet+ ammonemia + Ammonia enters brain Astrocytes form glutamine Osmotic swelling Cerebral Edema + Hepoöodema

APAP Overdose

Hypercatabolism (Catecholamines, cortisol, TNF-α, IL-1, IL-6 → Proteolysis)

Muscle Wasting → ↑ Ammonia Production

Liver Cannot Convert Ammonia to Urea → Astrocytes form glutamine → Osmotic swelling → Cerebral Edema +

Late Compensatory Anti-Inflammatory Response Syndrome (CARS); ↑ IL-4, IL-10, TGF-β → Immune Suppression → High Infection Risk

Further Organ Failure & Mortality