Liver disorders encephalopathy

Reye syndrome is a rare disorder in children, characterized by a combination of severe liver disorder and encephalopathy (central nervous system (CNS) disturbances) that can follow an acute viral illness and which has a relatively high mortality. It has been found to be... 

With respect to the correlation between liver disorders and the functions of the brain, discussion currently focuses on five hypotheses concerning the development of hepatic encephalopathy (7.) intoxication hypothesis, (2.) neurotransmitter hypothesis, (2.) deficiency hypothesis, (4.) synergistic neurotoxicity, and (J.) hypothesis of primary gliopathy. 

Very few adverse effects, generally of minor importance, have been reported (4). In immunosuppressed patients abnormal liver function, encephalopathy, and myelosuppression have been observed however, it is unclear at present whether these adverse effects are related to the drug itself or to the underlying disorder (5-7). 

The metabolic encephalopathies comprise a series of neurological disorders not caused by primary structural abnormalities rather, they result from systemic illness, such as diabetes, liver disease and renal failure. Metabolic encephalopathies usually develop acutely or subacutely and are reversible if the systemic disorder is treated. If left... 

Citrulline is exchanged for ornithine across the inner mitochondrial membrane by ORNT-1. Ornithine is produced in the cytosol as the final step in the urea cycle and must be returned to the mitochondrial matrix for transcarbamoyla-tion by OTC. A second ornithine-citrulline antiporter (ORNT-2) is also expressed in the liver mitochondria and may attenuate the severity of disease in patients with HHH (Hyperammonemia, Hyperornithinemia, Homocitrullinuria) disease due to ORNT-1 deficiency. This disorder typically manifests later in life with intermittent hyperammonemic encephalopathy and protein aversion. Intramitochondrial ornithine deficiency causes both hyperammonemia and hyperornithinemia due to a lack of substrate for OTC. Homocitrullinuria occurs due to the use of lysine by OTC as an alternate substrate. The diagnosis is confirmed by mutation analysis. 

Of as yet unknown consequence to the brain and nervous system, there are many studies indicating that valproic acid promotes a variety of potentially dangerous viruses (e.g., Fan et al., 2005). Both valproic acid and carbamazepine cause a small increase in the rate of major congenital malformations in infants (Wide et al., 2004). Acute and potentially fatal pancreatitis has been reported with valproic acid (e.g., Grauso-Eby et al., 2003). Liver failure is a known problem as well. Valproic acid is known to cause hyperammonemia with encephalopathy (e.g., McCall et al., 2004). Severe and even lethal skin disorders can occur with all of the antiseizure medications now used as mood stabilizers. The various adverse effects of valproic acid and other mood stabilizers are not nearly as benign as physicians believe in their eagerness to switch patients from lithium. 

A 17-year-old man developed toxic subacute hepatitis with grade II encephalopathy and coagulation disorders a few days after consuming ecstasy. Liver transplantation was performed and he recovered fully. 

GI pain and bleeding pulmonary edema anemia, destruction of red blood cells liver necrosis, kidney failure encephalopathy and other central and peripheral nervous system disorders. Chronic toxicity can lead to systemic hypotension skin disorders such as eczema, hyperkeratosis, melanosis, ulceration, skin cancers blood problems such as anemia, acute leukemia kidney failure delirium, encephalopathy, seizures, neuropathy. 

In the case of cerebral dysfunction, it is possible for these disorders to be reflected individually in differing states of intensity and in a variety of combinations. This results in a very varied pathophysiological and clinical picture of encephalopathy. Such a collective term for restrictions in the function of the brain does not, however, yield any statement as to their origins or pathogenesis. Encephalopathy can be triggered by some 50-60 disorders and aetiological factors - including liver diseases. (see chapter 15)... 

Hepatic encephalopathy (HE) is defined as a functional, potentially reversible disorder of the brain in the wake of severe (either acute or chronic) liver disease. The term comprises all neurological and mental symptoms. 

The acute or acute recurrent form can be equated with the manifestation of portosystemic encephalopathy in chronic liver disease. It is also known as acute episodic form . Discrete psychometric disorders usually precede the manifest picture as a latent stage. Manifestation includes stages I-IV and hence covers a wide spectrum of clinical, neurological and psychopathological symptoms. Once the liver function is stabilized and the trigger factors are eliminated, all the symptoms of this form are as a rule reversible. 

Disorders of cerebral functions on the one hand and of the water and electrolyte balance on the other hand are the earliest and most reliable hints of the onset of decompensation in severe liver disease, especially cirrhosis. In clinical terms, they can be easily diagnosed as latent hepatic encephalopathy (by carrying out psychometric tests) and/or latent oedema (by recording the increase in body weight). For this reason, these examination methods are also of fundamental importance in the follow-up of chronic liver disease, (s. fig. 15.3)... 

A 7-year-old boy with Duchenne muscular dystrophy and attention deficit hyperactivity disorder (ADHD) developed acute hepatic failure, with features of autoimmune hepatitis (2). The only medications he had taken were pemoline (56 mg/day) and cjrproheptadine (2 mg/day). Pemoline was withdrawn after 8 months as the presumed cause of his raised transaminases. Two weeks later he developed an altered mental state, jaundice, and encephalopathy. The histological features of the liver and his autoimmune antibody panel were consistent with autoimmune hepatitis. He was treated with corticosteroids and azathioprine and recovered. 

Weight gain, gastrointestinal symptoms, hair loss, and tremor are relatively common adverse effects. Sedation, fatigue, dizziness, headache, ataxia, insomnia, and behavioral problems are less frequent than with other anticonvulsants. Hyperammonemia is relatively common, but it is often asymptomatic. Fatal liver failure has an incidence of up to 1 600 in young infants, but is extremely rare in adults. Uncommon effects include parkinsonism, encephalopathy, pseudoatrophy of the brain, pancreatitis, and disorders of hemostasis (especially thrombocytopenia). 

The fasting venous plasma ammonia concentration is useful in the differential diagnosis of encephalopathy when it is unclear if encephalopathy is of an hepatic origin. It is especially helpful in diagnosing Reye s syndrome and the inherited disorders of urea metabolism. However, it is not a useful test to use in patients with laiown liver disease. 

Hepatic encephalopathy is a metabolic disorder characterized by a wide spectrum of neuropsychiatric dysfunction. It may occur as an acute syndrome in patients with acute hepatic failure from viral or drug-induced hepatitis or as a chronic syndrome associated with liver failure and cirrhosis. 

High doses of salicylates can cause hepatic injury. The onset of injury characteristically occurs after several months of treatment. The majority of cases occur in patients with connective tissue disorders. There usually are no symptoms, simply an increase in serum levels of hepatic transaminases, but some patients note right upper quadrant abdominal discomfort and tenderness. Overt jaundice is uncommon. The injury usually is reversible upon discontinuation of salicylates. The use of salicylates is contraindicated in patients with chronic liver disease. Salicylates are associated with the severe hepatic injury and encephalopathy observed in Reye s syndrome. 

Adams RD, Foley JM. The neurological disorder associated with liver disease. In Metabolic and Toxic Diseases of the Nervous System. (H.H. Merritt, and C.C. Hare, eds.)Vol. 32. WiUiams and Wilkins, Baltimore, USA, pp. 198-237, 1953 Ahboucha S, Butterworth RF. The neurosteroid system Implication in the pathophysiology of hepatic encephalopathy. Neurochem. Int., 52, 575-587, 2008 Ahboucha S, Pomier-Layrargues G, Mamer O, Butterworth RF. Increased brain concentrations of a neuroinhibitory steroid in human hepatic encephalopathy. Arm. Neurol, 58, 169-170, 2005 Ahboucha S, Coyne L, Hirakawa R, Butterworth RF, Halliwell RF. An interaction between benzodiazepines and neuroactive steroids at GABA receptors in cultured hippocampal neurons. Neurochem. Int., 48, 703-707, 2006... 

A 55-year-old woman who had received a liver transplant developed Hashimoto s encephalopathy after interferon therapy for hepatitis C virus accompanied by a lymphoproliferative disorder related to Epstein-Barr virus infection. Tacrolimus was withdrawn. She developed sudden loss of consciousness, convulsions, and cervical stiffness, which responded to prednisone. 

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