Introduction: Hepatic encephalopathy (HE) can present with a broad range of neuropsychiatric abnormalities and varying severity, as a result of hepatic insufficiency from acute liver failure or cirrhosis, or from portosystemic shunting, even in the absence of intrinsic liver disease.
Pathogenesis: The pathogenesis of this condition is not well defined. Accumulation of ammonia from the gut and other sources due to impaired hepatic clearance or portosystemic shunting can lead to accumulation of glutamine in brain astrocytes, leading to swelling, which can be aggravated by hyponatremia. Other mediators, such as benzodiazepine-like agonists, inflammatory cytokines, manganese, and neurosteroids, may play a role.
Diagnosis and Classification: There is no consensus on the diagnostic criteria for HE. Diagnosis requires the exclusion of other causes of altered mental status (Figure 1). In 1998, a consensus group at the 11th World Congress of Gastroenterology in Vienna proposed a standardized nomenclature for hepatic encephalopathy (Figure 2). Overt HE consists of neurological and psychiatric abnormalities that can be detected by bedside clinical tests, whereas minimal HE can only be distinguished by specific psychometric tests, as these patients have normal mental and neurological status on clinical exam. Overt HE occurs in at least 30 to 45% of patients with cirrhosis and in 10 to 50% of patients with transjugular intrahepatic portosystemic shunts. Minimal HE is estimated to develop in more than 60% of patients with cirrhosis.
Clinical Presentation: Patients with HE may present with alterations in intellectual, cognitive, emotional, behavioral, psychomotor, and fine motor skills. These can lead to personality changes, decreased energy level, impaired sleep-wake cycle, impaired cognition, diminished consciousness, asterixis, or loss of motor control. Although patients with HE may develop focal neurologic findings, such as hemiplegia, an alternative cause for a new focal neurologic deficit (e.g. intracerebral hemorrhage) should be investigated further.
Clinical Scales for Grading HE: Clinical diagnosis of overt HE is based on the combination of (a) impaired mental status, which is commonly graded by the West Haven Criteria (Figure 3) and (b) impaired neuromotor function, such as hyperreflexia, hypertonicity, and asterixis. To test for asterixis, the patient should extend their arms, dorsiflex their wrist, and hold this position (Figure 4). A positive test for asterixis is characterized by an involuntary flapping tremor at the wrist due to abnormal functioning of the motor centers that control the tone of muscles involved with maintaining posture. This tremor can also be seen in the tongue and lower extremities. If the patient is too somnolent to raise his or her hands, then oscillating grip strength is another means to test for asterixis. Parkinsonian-like symptoms, such as rigidity and tremors, can also be present. In addition to the classic West Haven Criteria, the Glasgow coma score (Figure 5) can be used for patients with grade 3 and 4 HE. The Hepatic Encephalopathy Scoring Algorithm (HESA) and Clinical Hepatic Encephalopathy Staging Scale (CHESS) have been used to grade HE in clinical trials but use is not widespread in clinical practice. The Spectrum of Neurocognitive Impairment in Cirrhosis (SONIC) was recently proposed at a HE expert consensus meeting as a means to grading the severity assessment of HE on a more continuous spectrum for future clinical studies.