Acute Liver Failure

Pathophysiology of cerebral oedema in acute liver failure

Authors: Scott TR, Kronsten VT, Hughes RD, Shawcross DL.

Cerebral oedema is a devastating consequence of acute liver failure (ALF) and may be associated with the development of intracranial hypertension and death. In ALF, some patients may develop cerebral oedema and increased intracranial pressure but progression to life-threatening intracranial hypertension is less frequent than previously described, complicating less than one third of cases who have proceeded to coma since the advent of improved clinical care. The rapid onset of encephalopathy may be dramatic with the development of asterixis, delirium, seizures and coma. Cytotoxic and vasogenic oedema mechanisms have been implicated with a preponderance of experimental data favouring a cytotoxic mechanism. Astrocyte swelling is the most consistent neuropathological finding in humans with ALF and ammonia plays a definitive role in the development of cytotoxic brain oedema. The mechanism(s) by which ammonia induces astrocyte swelling remains unclear but glutamine accumulation within astrocytes has led to the osmolyte hypothesis. Current evidence also supports an alternate 'Trojan horse' hypothesis, with glutamine as a carrier of ammonia into mitochondria, where its accumulation results in oxidative stress, energy failure and ultimately astrocyte swelling. Although a complete breakdown of the blood-brain barrier is not evident in human ALF, increased permeation to water and other small molecules such as ammonia has been demonstrated resulting from subtle alterations in the protein composition of paracellular tight junctions. At present, there is no fully efficacious therapy for cerebral oedema other than liver transplantation and this reflects our incomplete knowledge of the precise mechanisms underlying this process which remain largely unknown.

Noninvasive estimation of raised intracranial pressure using ocular ultrasonography in liver transplant recipients with acute liver failure -A report of two cases-

Authors: Kim YK, Seo H, Yu J, Hwang GS.

Intracranial pressure (ICP) monitoring is an important issue for liver transplant recipients, since increased ICP is associated with advanced hepatic encephalopathy or graft reperfusion during liver transplantation. Invasive monitoring of ICP is known as a gold standard method, but it can provoke bleeding and infection; thus, its use is a controversial issue. Studies have shown that optic nerve sheath diameter > 5 mm by ocular ultrasonography is useful for evaluating ICP > 20 mmHg noninvasively in many clinical settings. In this case report, we present experiences of using ocular ultrasound as a diagnostic tool that could detect changes in ICP noninvasively during liver transplantation.

Assessment and management of cerebral edema and intracranial hypertension in acute liver failure

Authors: Mohsenin V.

Acute liver failure is uncommon but not a rare complication of liver injury. It can happen after ingestion of acetaminophen and exposure to toxins and hepatitis viruses. The defining clinical symptoms are coagulopathy and encephalopathy occurring within days or weeks of the primary insult in patients without preexisting liver injury. Acute liver failure is often complicated by multiorgan failure and sepsis. The most life-threatening complications are sepsis, multiorgan failure, and brain edema. The clinical signs of increased intracranial pressure (ICP) are nonspecific except for neurologic deficits in impending brain stem herniation. Computed tomography of the brain is not sensitive enough in gauging intracranial hypertension or ruling out brain edema. Intracranial pressure monitoring, transcranial Doppler, and jugular venous oximetry provide valuable information for monitoring ICP and guiding therapeutic measures in patients with encephalopathy grade III or IV. Osmotic therapy using hypertonic saline and mannitol, therapeutic hypothermia, and propofol sedation are shown to improve ICPs and stabilize the patient for liver transplantation. In this article, diagnosis and management of hepatic encephalopathy and cerebral edema in patients with acute liver failure are reviewed.

Brain edema in acute liver failure and chronic liver disease: similarities and differences

Authors: Bosoi CR, Rose CF.

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that typically develops as a result of acute liver failure or chronic liver disease. Brain edema is a common feature associated with HE. In acute liver failure, brain edema contributes to an increase in intracranial pressure, which can fatally lead to brain stem herniation. In chronic liver disease, intracranial hypertension is rarely observed, even though brain edema may be present. This discrepancy in the development of intracranial hypertension in acute liver failure versus chronic liver disease suggests that brain edema plays a different role in relation to the onset of HE. Furthermore, the pathophysiological mechanisms involved in the development of brain edema in acute liver failure and chronic liver disease are dissimilar. This review explores the types of brain edema, the cells, and pathogenic factors involved in its development, while emphasizing the differences in acute liver failure versus chronic liver disease. The implications of brain edema developing as a neuropathological consequence of HE, or as a cause of HE, are also discussed.

A reproducible, clinically relevant, intensively managed, pig model of acute liver failure for testing of therapies aimed to prolong survival

Authors: Lee KC, Jimenez CP, Alibhai H, Chang YM, Leckie PJ, Baker LA, Stanzani G, L Priestnall S, Mookerjee RP, Jalan R, Davies NA.

BACKGROUND: A clinically relevant, translational large animal model of acute liver failure (ALF) is required for testing of novel therapies to prolong survival in acute liver failure, to permit spontaneous liver recovery or to act as a bridge to transplantation.
AIMS: The aim was to establish a pig model of acetaminophen-induced ALF that mimics the human clinical syndrome, is managed as in a human intensive care unit and has a predictable survival time.

Pretransplant Neurological Presentation and Severe Posttransplant Brain Injury in Patients With Acute Liver Failure

Authors: Tan WF, Steadman RH, Farmer DG, Hong JC, Busuttil RW, Apinyachon W, Xia VW.

BACKGROUND: Alterations in the central nervous system in patients with acute liver failure (ALF) present unique challenges in the perioperative period. In this retrospective study, we examined pretransplant neurological presentation and the incidence, clinical presentation, and risk factors associated with severe posttransplant brain injury (BI) in ALF patients undergoing orthotopic liver transplantation (OLT).
METHODS: After institutional review board approval, ALF patients who underwent OLT between 2004 and 2010 at our center were reviewed. Pretransplant neurological presentation and severe posttransplant BI were examined. Risk factors for the latter were identified.
RESULTS: During the study period, 90 (67 adults and 23 children) ALF patients underwent primary OLT. Preoperatively, all patients developed encephalopathy, 6 had seizure activity, 32 had radiological evidence of cerebral edema, and 11 had severe cerebral edema. After OLT, 7 patients developed severe posttransplant BI. Of these 7 patients, 4 had brain death, and 3 had irreversible injury that precluded them from living independently. Severe pretransplant cerebral edema and a higher posttransplant international normalized ratio (odds ratios and 95% confidence intervals: 50.2, 5.8-433.5 and 3.1, 1.1-8.8 , respectively) were risk factors associated with severe posttransplant BI.
CONCLUSIONS: Pretransplant neurological complications were prevalent, and severe posttransplant BI occurred at a rate of 7.8% and was significantly associated with severe pretransplant cerebral edema and postoperative international normalized ratio. Our findings support the use of pretransplant computed tomography. If severe pretransplant cerebral edema is confirmed, efforts should be made to aggressively control intracranial pressure and select a proper donor to minimize the risk of severe posttransplant BI and futile transplantation.

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