Correlation Between Ammonia Levels and the Severity of Hepatic Encephalopathy

Ong, JP; Aggarwal, Ashish; Krieger, Derk; Easley, K; Karafa, MT; Lente, F Van; Arroliga, A. C.; Kd, Mullen

doi:10.1177/0115426504019004413a

Cited by 97 publications

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“…16 The arterial ammonia level measured within 24 h of patient presentation has also been demonstrated to correlate with patient outcome in ALF, unlike the case in cirrhosis. 4,17 A study conducted by us documented that non-survivors had significantly higher median ammonia levels than survivors (174.7 v 105.0 mmol/L; P, 0.001) in patients with ALF. 4 An arterial ammonia level of >124 mmol/L was found to predict mortality with 78.6% sensitivity and 76.3% specificity, and had 77.5% diagnostic accuracy.…”

Section: Role Of Ammoniamentioning

confidence: 98%

Management in Acute Liver Failure

Shalimar

Acharya

2015

Journal of Clinical and Experimental Hepatology

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Acute liver failure (ALF) is a rare, potentially fatal complication of severe hepatic illness resulting from various causes. In a clinical setting, severe hepatic injury is usually recognised by the appearance of jaundice, encephalopathy and coagulopathy. The central and most important clinical event in ALF is occurrence of hepatic encephalopathy (HE) and cerebral edema which is responsible for most of the fatalities in this serious clinical syndrome. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a central role in the pathogenesis. The role of newer ammonia lowering agents is still evolving. Liver transplant is the only effective therapy that has been identified to be of promise in those with poor prognostic factors, whereas in the others, aggressive intensive medical management has been documented to salvage a substantial proportion of patients. A small fraction of patients undergo liver transplant and the remaining are usually treated with medical therapy. Therefore, identification of the complications and causes of death in such patients, and use of appropriate prognostic models to identify those who need liver transplant and those who can be managed with medical treatment is a vital component of therapeutic strategy. In this review, we discuss the various pathogenetic mechanisms and treatment options available. ( J CLIN EXP HEPATOL 2015;5:S104-S115)A cute liver failure (ALF) can be a fatal complication of acute hepatic injury and occurs unpredictably. It is a rare clinical entity marked by the sudden loss of hepatic function and a severe life-threatening course in a person with no prior history of liver disease. ALF represents a syndrome rather than a specific disease, having multiple causes that vary in course and outcome. ALF is difficult to identify in its early stages, resulting in frequent delays in initiation of treatment. The causes of ALF include viral hepatitis, drug induced and toxin-induced liver damage, metabolic errors, ischemia, and miscellaneous rare causes.ALF is defined by three criteria: (1) rapid development of hepatocellular dysfunction (jaundice, coagulopathy), (2) encephalopathy, and (3) absence of a prior history of liver disease. 1 However, the interval between onset of acute hepatic injury (jaundice) and onset of liver failure (encephalopathy with or without coagulopathy) in such patients (icterus-encephalopathy interval; IEI) has been described to be between 4 weeks (Indian definition) 2-4 to 24 weeks (AASLD-ALF study group). 5 Further, due to the diverse natural course, ALF has been sub-classified as hyperacute (IEI # 7 day), acute (IEI # 4 weeks) and sub-acute ALF (IEI $ 5 week to #12 weeks) by British authors. 6 Despite these differences in definitions, the central and most important clinical event in ALF is occurrence of hepatic encephalopathy (HE) and cerebral edema which is responsible for most of the fatalities in this serious clinical syndrome. The pathogenesis of encephalopathy and cerebral edema in ALF is unique an...

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Section: Role Of Ammoniamentioning

confidence: 98%

Management in Acute Liver Failure

Shalimar

Acharya

2015

Journal of Clinical and Experimental Hepatology

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“…This suggests a direct link between hyperammonemia, brain ammonia and ICP (possibly brain edema). In CLD, HE patients often present elevated arterial ammonia concentrations; however, in contrast with ALF, the correlation between ammonia and severity of HE remains controversial , Kundra et al, 2005, Nicolao et al, 2003, Ong et al, 2003and Weissenborn et al, 2007. This infers other factors may be implicated in the pathogenesis of HE.…”

Section: Ammoniamentioning

confidence: 99%

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

Bosoi

Rose

2013

Neurochemistry International

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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. HighlightsBrain edema is a common feature in ALF and CLD. HE is inconsistently associated with the presence of brain edema. Fibrous and protoplasmic astrocytes are differentially implicated in the pathogenesis of HE. The pathogenesis of HE is multifactorial causing an array of neurological symptoms.

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“…18,19 This finding has been replicated with one such study showing that 69% of individuals with no overt signs of HE had elevated blood ammonia levels, whilst a number of patients with more significant grade 3 or 4 HE had either normal or only slightly elevated levels of ammonia in their blood. 20 This is in contrast to ALF whereby the relationship between blood ammonia levels and the clinical severity of HE is more clear-cut. Bernal and colleagues demonstrated ammonia to be an independent risk factor for the development of both HE and ICH, with the latter occurring in 55% of patients with blood ammonia concentrations >200 mmol/L.…”

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confidence: 99%

Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

Aldridge

Tranah

Shawcross

2015

Journal of Clinical and Experimental Hepatology

222

180

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The syndrome we refer to as Hepatic Encephalopathy (HE) was first characterized by a team of Nobel Prize winning physiologists led by Pavlov and Nencki at the Imperial Institute of Experimental Medicine in Russia in the 1890's. This focused upon the key observation that performing a portocaval shunt, which bypassed nitrogen-rich blood away from the liver, induced elevated blood and brain ammonia concentrations in association with profound neurobehavioral changes. There exists however a spectrum of metabolic encephalopathies attributable to a variety (or even absence) of liver hepatocellular dysfunctions and it is this spectrum rather than a single disease entity that has come to be defined as HE. Differences in the underlying pathophysiology, treatment responses and outcomes can therefore be highly variable between acute and chronic HE. The term also fails to articulate quite how systemic the syndrome of HE can be and how it can be influenced by the gastrointestinal, renal, nervous, or immune systems without any change in background liver function. The pathogenesis of HE therefore encapsulates a complex network of interdependent organ systems which as yet remain poorly characterized. There is nonetheless a growing recognition that there is a complex but influential synergistic relationship between ammonia, inflammation (sterile and non-sterile) and oxidative stress in the pathogenesis HE which develops in an environment of functional immunoparesis in patients with liver dysfunction. Therapeutic strategies are thus moving further away from the traditional specialty of hepatology and more towards novel immune and inflammatory targets which will be discussed in this review. ( J CLIN EXP HEPATOL 2015;5:S7-S20) H epatic encephalopathy (HE) is the term used to encapsulate the broad spectrum of neuropsychiatric disturbances associated with both acute and chronic liver failure (ALF and CLF, respectively), as well as porto-systemic bypass in the absence of hepatocellular disease. The clinical manifestations of HE can be extremely heterogeneous in nature, with symptoms presenting anywhere on a continuum spanning from seemingly normal cognitive performance, right the way through to states of confusion, stupor and coma. In between these extremes, patients with HE may exhibit signs such as inattentiveness, blunted affect, impairment of memory or reversal of the sleep-wake cycle, as well as physical manifestations such as tremor, myoclonus, asterixis and deep tendon hyperreflexia.ALF is defined by the onset of coagulopathy alongside any degree of encephalopathy in patients with no evidence of pre-existing liver disease. 1 The presence of HE in those with ALF is prognostic, with up to a quarter of cases developing raised intracranial pressure. 2 Patients presenting with ALF are at risk of developing its cardinal, lifethreatening feature, cerebral edema. Left untreated, cerebral edema can rapidly progress to cause herniation of the uncus through the falx cerebri, leading to compression of the brainstem and, ultimately, death. H...

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Correlation Between Ammonia Levels and the Severity of Hepatic Encephalopathy

Cited by 97 publications

References 0 publications

Management in Acute Liver Failure

Management in Acute Liver Failure

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

Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

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