الفهرس 
Acute liver failureOnly 14 pages are availabe for public view
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Abstract
ALF is a potentially life threatening condition that can developed from various etiologies, mainly viral hepatitis either hepatotropic or non hepatotropic viruses, drug causes (mainly acetaminophen hepatitis) ,vascular causes ,metabolic causes, autoimmune ,or malignancy causes.
Morbidity and mortality remain high as there is rapid deterioration of hepatic function in a previously healthy individual, patients clinically presented with janndice, encephalopathy and on examination there are hypotention, tachycardia, ascities, heamatemesis, melena, signs of cerebral edema and increased ICP (papilledema, hypertention, and bradycardia), tender liver either small (as in hepatic necrosis)or enlarged (as in congestive heart failure,viral hepatits,or Budd- Chiari syndrome.
Many investigations should be done to confirm the diagnosis, to exclude the cause of ALF and to reveal any accompanied complications.
laboratory tests including CBC, PT, liver enzymes (SGPT,SGOT), S.bilirubin, S.ammonia, S.lactate, S.glucose, S.creatinine, S.free cupper, S.phosphate, blood culture, viral serology (HAV-IgM, HbsAg, HCV-Ab, HDV-IgM, CMV, HSV), acetaminophen level and autoimmune markers (ANA-Ab, ASM-Ab).Imaging syudies include abdominal U/S, CT, MRI, EEG, liver biopsy.
Management focused on identifying the cause(s) of the liver insult and supportive management in the intensive care unit including liver transplantation when clinically indicated and early recognition of the ALF-associated complications
The initiating insult which causes liver injury leads to activation of innate immune system namely KCs, MQ, and NK complement system activation. These in turn lead to increase level of proinflammatory cytokines including IL-1, IL-6, TNF-α and PAF, leading to SIRS. The counter haemostatic release of anti-inflammatory cytokines including IL-4, IL-10, TGFB, PGE2, monocyte deactivation and macrophage dysfunction will lead to CARS.
Loss of immune balance between systemic pro-inflammatory and compensatory anti-inflammatory profiles results in immune dysfunction leading to MODS and death.
Kc and MQ are responsible for antigen presentation, secrete cytokines and phagocytosis.
NK cells produce INF- γ on activation; they are regulated by kupffer cell - derived cytokines.
NKT cells release IL-4 and INF-γ, so it increases ALF damage.
Monocyte secretes large quantities of pro-inflammatory cytokines.
LSECs clear proinflammatory substance, secrete IL-10, IL-8,and PAF.
Neutrophils early response to liver injury , cellular stress, or systemic inflammation.
Eosinophils increase in fulminant hepatic failure.
Inflammatory cytokine in ALF:
Hepato-protective:
IL-6 inhibits NKT-cell and induces anti-apoptosis through activation of STAT3 signaling pathway.
IL-10 (at the onset of hepatic injury) upregulation of pro-inflammatory cytokine and the effectors like TNF-α, IL-1 and superoxide dismutase.
PGE1
Hazardous cytokine:
IL-10 (late in the regenerative stage) inhibits release of pro-inflammatory cytokine and inhibits macrophage cytotoxic activity.
TNF-α cause hepatocyte apoptosis through interaction with TNF- receptor 1.
INF-γ stimulates cytotoxic T-lymphocyte and up regulates Fas on hepatocyte causing liver cell apoptosis.
MIF stimulates inflammatory response through stimulation of cytokine production and stimulates cellular recruitment.
IL-18(a member of IL-1 super family) increase TNF- α, IL-10 and IL-8, it also facilitates INF-γ secretion.
TGFB inhibits macrophage cytotoxic activity and inhibits cytokine production.
PGE2