Hepatic Encephalopathy[edit | edit source]
Hepatic encephalopathy is a neuropsychiatric syndrome caused by liver disease. It occurs most often in patients with cirrhosis but also occurs in acute hepatic failure. Aetiology Hepatic encephalopathy is thought to be due to a biochemical disturbance of brain function because it is reversible and does not cause marked pathological changes in the brain. Liver failure and portosystemic shunting of blood are two important factors underlying hepatic encephalopathy and the balance between these varies in different patients. Some degree of liver failure is a constant factor as portosystemic shunting of blood hardly ever causes encephalopathy if liver function is normal. Little is known of the biochemical 'neurotoxins' causing the encephalopathy, but they are thought to be mainly nitrogenous substances produced in the gut, at least in part by bacterial action, which are normally metabolised by the healthy liver so that they do not enter the systemic circulation. Ammonia has long been considered an important factor but much interest has centred recently on gamma-aminobutyric acid. Additional putative culprit substances include other false neurotransmitters such as octopamine, amino acids, mercaptans and fatty acids. Some factors appear to precipitate hepatic encephalopathy by increasing the availability of these substances; in addition, the brain in cirrhosis may be sensitised to other factors such as drugs that are able to precipitate hepatic encephalopathy. Disruption of the function of the blood-brain barrier is a feature of acute hepatic failure and may lead to cerebral oedema.
These include changes of intellect, personality, emotions and consciousness, with or without neurological signs. When an episode develops acutely a precipitating factor may be found . The earliest features are very mild but, as the condition becomes more severe, apathy, inability to concentrate, confusion, disorientation, drowsiness, slurring of speech and eventually coma develop. Convulsions sometimes occur. Examination usually shows a flapping tremor (asterixis), inability to perform simple mental arithmetic tasks or draw objects such as a star (constructional apraxia), and, as the condition progresses, hyper-reflexia and bilateral extensor plantar responses. Hepatic encephalopathy rarely causes focal neurological signs, and if these are present, other causes must be sought. Fetor hepaticus, a sweet musty odour to the breath, is usually present but is more a sign of liver failure and portosystemic shunting than of hepatic encephalopathy. Rarely, chronic hepatic encephalopathy (hepatocerebral degeneration) gives rise to variable combinations of cerebellar dysfunction, Parkinsonian syndromes, spastic paraplegia and dementia. Investigations The diagnosis can usually be made clinically, but when doubt exists an electroencephalogram (EEG) shows diffuse slowing of the normal alpha waves with eventual development of delta waves. The arterial ammonia is usually increased in patients with hepatic encephalopathy. However, increased concentrations can occur in the absence of clinical encephalopathy so this investigation is of little or no diagnostic value.
EBM: TREATMENT OF HEPATIC ENCEPHALOPATHY 'Studies in small numbers of patients have shown lactulose to be of benefit in both acute and chronic hepatic encephalopathy but large RCTs are lacking.' 'Neomycin treatment is not significantly better than placebo in treating acute hepatic encephalopathy.' 'Current evidence does not support the use of branched-chain amino acid solutions in either acute or chronic hepatic encephalopathy.' * Simmons F, Goldstein H, Boyle JD. A controlled clinical trial of lactulose in hepatic encephalopathy. Gastroenterology 1970; 59:827-832. * Elkington SG, Floch MH, Conn HO. Lactulose in the treatment of chronic portal-systemic encephalopathy. A double-blind clinical trial. N Engl J Med 1969; 281:408-412. * Strauss E, Tramote R, Silva EP, et al. Double-blind randomized clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy. Hepatogastroenterology 1992; 39:542-545. * Morgan MY. Branched chain amino acids in the management of chronic liver disease. Facts and fantasies. J Hepatol 1990; 11:133-141.
Episodes of encephalopathy are common in cirrhosis and are usually readily reversible until the terminal stages occur. The principles of management are to treat or remove precipitating causes, to reduce protein intake, and to suppress production of neurotoxins by bacteria in the bowel. Dietary protein is reduced to less than 20 g/day, and glucose (300 g/day) is given orally or parenterally in severe cases. As encephalopathy improves, dietary protein is increased by 10-20 g/day every 48 hours to an intake of 40-60 g/day, which is usually the limit in cirrhotic patients. Lactulose (15-30 ml 8-hourly) is a disaccharide which is taken orally and reaches the colon intact to be metabolised by colonic bacteria. The dose is increased gradually until the bowels are moving twice daily. It produces an osmotic laxative effect, reduces the pH of the colonic content, thereby limiting colonic ammonia absorption, and promotes the incorporation of nitrogen into bacteria (see EBM panel). Lactitol is a rather more palatable alternative to lactulose, with a less explosive action on bowel function. Neomycin (1-4 g 4-6-hourly) is an antibiotic which acts by reducing the bacterial content of the bowel. It can be used in addition or as an alternative to lactulose if diarrhoea becomes troublesome. Neomycin is poorly absorbed from the bowel but sufficient gains access to the body to contraindicate its use when uraemia is present. It is less desirable than lactulose for long-term use; ototoxicity is the main deleterious effect. Chronic or refractory hepatic encephalopathy is one of the main indications for liver transplantation.