Hepatic Disorders

Cognitive impairment is common in patients with advanced liver disease, regardless of the etiology. Hepatic encephalopathy is a syndrome characterized by a spectrum of neuropsychiatric manifestations as a complication of hepatic insufficiency or portosystemic shunting. The symptoms may range from subclinical forms, only detected in neuropsychological tests, to severe cases of hepatic coma. Overt manifestations begin with subtle psychomotor slowing, reversal of sleep-wake cycle, and some mental abnormalities (inattention, disorientation, lack of awareness), progressing to mood disorders (euphoria, depression, irritability, anxiety), personality changes, and inappropriate behavior. Agitation and aggression can evolve to impairment of consciousness, leading to progressive stupor and coma. Neurological examination may develop later asterixis, paratonia, pyramidal signs, and extensor posturing. The diagnosis is mostly clinical and based on the exclusion of other conditions that cause impaired cognition. High arterial ammonia levels may support the diagnosis, but should not be used alone to perform the diagnosis because they are not consistently increased. Brain imaging is useful in order to exclude structural lesions, and the EEG may find typical changes in different stages of the encephalopathy. Prompt management of hepatic encephalopathy is essential because symptoms are potentially, partial or fully, reversible with appropriate treatment. Basically, it includes nutritional support, treatment of precipitant factors (such as sedatives, gastrointestinal bleeding, constipation, infections, hypovolemia, hypokalemia, acidosis), reducing gut amnoniagenesis (with nonabsorbable disaccharides like lactulose, enemas, oral antibiotics like neomycin and rifaximin, and probiotics), and, finally, modification of portosystemic shunts. Moreover, further events should be actively prevented, and liver transplantation should be considered in all suitable candidates. Despite its potential reversibility, hepatic encephalopathy is an indicator of poor prognosis and correlates with mortality in patients with acute liver failure as well as end-stage liver disease.

Another rarer neuropsychiatric syndrome associated with chronic liver disease is the acquired hepatocerebral degeneration characterized by progressive neuropsychiatric and movement disorder. The clinical picture usually has a subacute onset with slow initial course and includes cognitive and psychiatric manifestations (attention deficit, visual-spatial dysfunction, apathy, excessive somnolence, lethargy) and even dementia, combined with parkinsonian and cerebellar signs (such as tremor, akinesia, chorea, dystonia, myoclonus, dysarthria, ataxia), but also pyramidal signs, and sometimes myelopathy, very similar to the hereditary hepatocerebral degeneration Wilson disease. Some patients may present with concomitant episodes of acute hepatic encephalopathy overlapping the clinical course of acquired hepatocerebral degeneration, sometimes challenging disease differentiation. Moreover, there is no agreement in the literature if recurrent episodes of hepatic encephalopathy are an essential factor in acquired hepatocerebral degeneration occurrence. The pathogenesis remains unclear, but is thought to be due to intracerebral accumulation of manganese, suggested by a paramagnetic material deposition observed as globus pallidus hyperintensities on brain MRI Tl-weighted sequences. Furthermore, some patients with advanced liver disease, but without a clinical picture of acquired hepatocerebral degeneration, may also show basal ganglia hyperintensities, mostly those who exhibit episodes of hepatic encephalopathy, aside from perhaps a less extensive involvement of basal ganglia and other brain structures. Whether acquired hepatocerebral degeneration is reversible remains controversial, but liver transplantation and chelators such as trientine may be helpful to ameliorate clinical symptoms. Indeed, liver transplantation is regarded as the main effective therapy; nonetheless, there are also cases of patients whose neurological manifestations do not improve or even recur after hepatic transplant [87, 88].

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