Hepatic encephalopathy: Suspect it early in patients with cirrhosis
ABSTRACTAs viral hepatitis and nonalcoholic fatty liver disease continue to increase in prevalence, we will see more cases of hepatic encephalopathy. Primary care physicians are often the first to suspect it, as they are familiar with the patient’s usual mental and physical status. This serious complication typically occurs in patients with severe comorbidities and requires multidisciplinary evaluation and care.
KEY POINTS
- Hepatic encephalopathy should be considered in any patient with cirrhosis who presents with neuropsychiatric manifestations in the absence of another brain disorder, such as stroke or brain tumor.
- “Minimal” hepatic encephalopathy may not be obvious on clinical examination but can be detected with neurophysiologic and neuropsychiatric testing.
- Every cirrhotic patient is at risk; potential precipitating factors should be addressed during regular clinic visits.
- Management requires prompt identification of precipitating factors and initiation of empiric medical therapy. Current treatments include drugs to prevent ammonia generation in the colon.
- Long-acting benzodiazepines should not be used to treat sleep disorders in patients with cirrhosis, as they may precipitate encephalopathy.
Special tests may be needed to detect subclinical hepatic encephalopathy
In subclinical hepatic encephalopathy, the apparent lack of manifestations poses a great diagnostic challenge, but a thorough history may uncover poor social interaction, personality changes, poor performance at work, and recent traffic violations or motor vehicle accidents. Primary care physicians are usually the first to suspect the condition because they are familiar with the patient’s baseline mental and physical conditions.
For example, the primary care physician may notice decreased attention and worsening memory during a follow-up visit, or the physician may ask whether the patient has difficulty with work performance and handwork (psychomotor and fine motor skills), and whether there have been traffic violations or car accidents (visuospatial skills). Such clues, although not restrictive, may help identify patients with minimal hepatic encephalopathy and prompt referral for neuropsychiatric testing.
Neurologic deficits described in the subclinical form are in the domains of attention and concentration, working memory, visuospatial ability, and fine motor skills; communication skills remain intact.35 These deficits are not reliably detected on standard clinical evaluation but can be detected by neuropsychiatric and neurophysiologic testing.
While several tests for minimal hepatic encephalopathy have been developed, they need to be validated in large trials in the United States.
Neurophysiologic tests include electroencephalography and auditory or visual event-related P300 (evoked potential) testing.
Neuropsychiatric tests traditionally involved several batteries administered and interpreted by specialized personnel. They were time-consuming and were not practical in a typical office setting. They were later refined into the Psychometric Hepatic Encephalopathy Score test (ie, the PSE syndrome test).36 This combines a digit symbol test, a serial dotting test, a line-tracing test, and a number-connection or figure-connection test. An abnormal result in at least three of the four subtests constitutes an overall abnormal PSE syndrome test.
The PSE syndrome test has been validated for standard use in Germany, Spain, Italy, the United Kingdom, and India.35 In 1999, the Working Group on Hepatic Encephalopathy designated it as the official test for minimal hepatic encephalopathy.1 But the test has not been validated for use in the United States. Other tests have been developed, but their use is also limited by a lack of validation and by copyright laws. These factors constitute major obstacles to the diagnosis of subclinical hepatic encephalopathy in the United States. Nonetheless, physicians who suspect minimal hepatic encephalopathy may start lactulose therapy37 and schedule frequent follow-up visits to address and manage potential precipitating factors for overt hepatic encephalopathy.
Staging the severity of the encephalopathy
It is essential to exclude stroke, cerebral bleeding, and brain tumor before making a diagnosis of a first episode of hepatic encephalopathy. Thereafter, such exclusion must be guided by whether the patient has risk factors for these conditions or persistent symptoms of encephalopathy that do not respond to medical therapy.
Laboratory tests can identify metabolic derangements
Although laboratory tests are not diagnostic for hepatic encephalopathy, they can identify metabolic derangements that could contribute to it.
Imaging can help exclude other diagnoses
Neurophysiologic imaging studies such as magnetic resonance spectroscopy, magnetic transfer imaging, and water-mapping techniques have helped elucidate pathologic mechanisms of hepatic encephalopathy and are available in research centers, but they are not currently considered for diagnosis.
SEVERAL LINES OF TREATMENT
Treatment of hepatic encephalopathy involves a preemptive approach to address potential precipitating factors, medical therapy to reduce the production and absorption of ammonia from the gut, and surgical or interventional therapies. A multidisciplinary approach for testing the severity of neurologic impairment and response to therapy is needed to help determine if and when liver transplantation is required.
Prevent potential precipitating factors
An important concept in managing hepatic encephalopathy is to recognize that every cirrhotic patient is at risk and to make an effort to address potential precipitating factors during regular clinic visits. This includes reviewing medication dosing and adverse effects, emphasizing abstinence from alcohol and other toxic substances, and preventing bleeding from esophageal varices with endoscopic band ligation.
