hepatic encephalopathy
Hepatic encephalopathy (HE), also known as portosystemic encephalopathy (PSE), refers to a spectrum of neuropsychiatric abnormalities occurring in patients with liver dysfunction and portal hypertension. It results from exposure of the brain to excessive amounts of ammonia.
Terminology
Hepatic encephalopathy (HE) specifically refers to an encephalopathy occurring in patients with acute liver failure, a portosystemic shunt, or chronic liver disease. HE is generally regarded as a reversible condition, although the long-term sequelae are being further studied .
Hepatic encephalopathy may be subclassified according to severity and pattern (acute episode, recurrent, or persistent) .
Chronic neurological damage ascribed to repeated episodes of hepatic encephalopathy is usually termed acquired hepatocerebral degeneration, which is discussed separately.
For the purposes of this article, we use the terms separately and discussion here is limited to acute hepatic encephalopathy.
Epidemiology
The vast majority of patients have portosystemic shunts in the setting of cirrhosis, either from the development of spontaneous shunting or as a result of transjugular intrahepatic portosystemic shunting (TIPS) . The clinical spectrum can rarely manifest in individuals who have portosystemic bypass without any associated intrinsic hepatocellular disease. The broader term "portosystemic encephalopathy" can be used for this reason.
Clinical presentation
The clinical manifestations of hepatic encephalopathy range widely from chronic episodic subclinical neurological dysfunction to acute fulminant neurological impairment, coma and death .
The latest consensus guidelines published in 2014 from American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) states that hepatic encephalopathy can be classified according to:
In its lowest expression, hepatic encephalopathy can only cause memory leaks and visuospatial ability alterations. However, as it progresses, behavioral alterations and agitation appear, leading to obnubilation and coma in last stages. A classically described manifestation of hepatic encephalopathy is asterixis or flapping tremor, which appears in intermediate phases. Its presence indicates an overt hepatic encephalopathy.
In the majority of patients, a superimposed precipitating cause rather than worsening of hepatocellular function can be identified (particularly in acute situations). Such precipitants include:
- infection (most common): 50%
- excessive nitrogen-containing intestinal load
- gastrointestinal bleed (e.g. from varices)
- dietary intake of large quantities of protein (e.g. meat)
- reduced nitrogen excretion
- constipation
- renal failure
- metabolic or drug interactions
- hyponatremia or hypokalemia (e.g. from diuretics)
- sedatives
Grading
The most commonly used and accepted clinical grading system for hepatic encephalopathy is the West Haven criteria based on level of consciousness as well as cognitive and behavioral assessment:
- grade 0: no alteration in consciousness, intellectual function, personality or behavior
- grade 1: trivial lack of awareness, euphoria or anxiety, shortened attention span, impairment of addition or subtraction
- grade 2: lethargy or apathy, mild personality change, disorientation to time or place, inappropriate behavior
- grade 3: somnolence to semi-stupor but responsive to verbal stimuli, confusion, gross disorientation
- grade 4: coma, no response to verbal or noxious stimuli
Pathology
In hepatic encephalopathy, due to portosystemic shunting, ammonia from the digestive system or from elsewhere, which is usually metabolized by the liver reaches the systemic circulation. Although the exact mechanism of neurotoxicity has not been elucidated, ammonia is taken up by the brain and has been shown to be toxic to both astrocytes and neurons .
Radiographic features
MRI
MR imaging features of acute hyperammonemia include:
- T2/FLAIR
- mild
- symmetric high signal within the insula (most common), thalamus, and posterior limbs of the internal capsule, and cingulate gyrus
- often reversible with therapy
- severe
- diffuse cortical edema and hyperintensity
- perirolandic and occipital regions are typically spared
- mild
- DWI
- similar distribution to T2/FLAIR
- reverse with appropriate therapy
- SWI
- nearly one-half have microhemorrhages of white matter or cortex
- number and presence of microhemorrhages do not affect the outcome
- nearly one-half have microhemorrhages of white matter or cortex
- MR spectroscopy
- may show an elevated glutamine/glutamate peak coupled with decreased myoinositol and choline signals on proton MR spectroscopy
As the vast majority of cases of acute hepatic encephalopathy will be encountered in patients with established and chronic liver disease, chronic findings of acquired hepatocerebral degeneration are also usually present.
Treatment and prognosis
Acute hepatic encephalopathy can be rapidly fatal, while chronic hepatic encephalopathy tends to be a more indolent process. Identifying and treating precipitating cause is important, and leads to resolution in up to 80% of patients .
Treatment usually entails the careful cessation of any offending agents (e.g. toxins, chemotherapeutic agents, antiepileptic agents), treating contributing conditions (e.g. sepsis, GI bleeding), nutritional support (including the use of lactulose), and in some cases hemofiltration to remove excess ammonia.
Notably, the extent of severity on FLAIR and DWI correlates with the plasma ammonia level . More severe cases of diffuse cortical involvement (particularly on DWI) can be reversible but are more likely to be fatal, indicating the need for prompt therapy to treat the hyperammonemia in acute hepatic encephalopathy .
Differential diagnosis
The differential diagnosis includes other causes of hyperammonemic encephalopathy
- valproate-induced hyperammonemia
- adult-onset citrullinemia
- late-onset ornithine transcarbamylase deficiency
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Assoziationen und Differentialdiagnosen zu Hepatische Enzephalopathie: