of nursing care, such as an intensive care unit, is required, and intubation of the airway is often necessary to prevent life-threatening complications (e.g., aspiration or respiratory failure). placement of a nasogastric tube permits the safe administration of nutrients and medication. the treatment of hepatic encephalopathy depends on the suspected underlying cause (types a, b, or c) and the presence or absence of underlying causes. if encephalopathy develops in acute liver failure (type a), even in a mild form (grade 1–2), it indicates that a liver transplant may be required, and transfer to a specialist centre is advised. hepatic encephalopathy type b may arise in those who have undergone a tips procedure; in most cases this resolves spontaneously or with the medical treatments discussed below, but in a small proportion of about 5%, occlusion of the shunt is required to address the symptoms. in hepatic encephalopathy type c, the identification and treatment of alternative or underlying causes is central to the initial management. given the frequency of infection as the underlying cause, antibiotics are often administered empirically (without knowledge of the exact source and nature of the infection). once an episode of encephalopathy has been effectively treated, a decision may need to be made on whether to prepare for a liver transplant. diet in the past, it was thought that consumption of protein even at normal levels increased the risk of hepatic encephalopathy. this has been shown to be incorrect. furthermore, many people with chronic liver disease are malnourished and require adequate protein to maintain a stable body weight. a diet with adequate protein and energy is therefore recommended. dietary supplementation with branched-chain amino acids has shown improvement of encephalopathy and other complications of cirrhosis. some studies have shown benefit of administration of probiotics ("healthy bacteria"). lactulose/lactitol lactulose and lactitol are disaccharides that are not absorbed from the digestive tract. they are thought to decrease the generation of ammonia by bacteria, render the ammonia inabsorbable by converting it to ammonium (nh4+) ions, and increase transit of bowel content through the gut. doses of 15-30 ml are typically administered three times a day; the result is aimed to be 3–5 soft stools a day, or (in some settings) a stool ph of <6.0. lactulose may also be given by enema, especially if encephalopathy is severe. more commonly, phosphate enemas are used. this may relieve constipation, one of the causes of encephalopathy, and increase bowel transit. lactulose and lactitol are beneficial for treating hepatic encephalopathy, and are the recommended first-line treatment. lactulose does not appear to be more effective than lactitol for treating people with hepatic encephalopathy. side effects of lactulose and lactitol include the possibility of diarrhea, abdominal bloating, gassiness, and nausea. in acute liver failure, it is unclear whether lactulose is beneficial. the possible side effect of bloating may interfere with a liver transplant procedure if required. antibiotics the antibiotic rifaximin may be recommended in addition to lactulose for those with recurrent disease. it is a nonabsorbable antibiotic from the rifamycin class. this is thought to work in a similar way to other antibiotics but without the complications attached to neomycin or metronidazole. due to the long history and lower cost of lactulose use, rifaximin is generally only used as a second-line treatment if lactulose is poorly tolerated or not effective. when rifaximin is added to lactulose, the combination of the two may be more effective than each component separately. rifaximin is more expensive than lactulose, but the cost may be offset by fewer hospital admissions for encephalopathy. the antibiotics neomycin and metronidazole are other antibiotics used to treat hepatic encephalopathy. the rationale of their use was the fact that ammonia and other waste products are generated and converted by intestinal bacteria, and killing these bacteria would reduce the generation of these waste products. neomycin was chosen because of its low intestinal absorption, as neomycin and similar aminoglycoside antibiotics may cause hearing loss and kidney failure if used by injection. later studies showed that neomycin was indeed absorbed when taken by mouth, with resultant complications. metronidazole, similarly, is less commonly used because prolonged use can cause nerve damage, in addition to gastrointestinal side effects. l-ornithine and l-aspartate the combination of l-ornithine and l-aspartate (lola) lowers the level of ammonia in a person's blood. very weak evidence from clinical trials indicates that lola treatment may benefit people with hepatic encephalopathy. lola lowers ammonia levels by increasing the generation of urea through the urea cycle, a metabolic pathway that removes ammonia by turning it into the neutral substance urea. lola may be combined with lactulose and/or rifaximin if these alone are ineffective at controlling symptoms. epidemiology and prognosis in those with cirrhosis, the risk of developing hepatic encephalopathy is 20% per year, and at any time about 30–45% of people with cirrhosis exhibit evidence of overt encephalopathy. the prevalence of minimal hepatic encephalopathy detectable on formal neuropsychological testing is 60–80%; this increases the likelihood of developing overt encephalopathy in the future. once hepatic encephalopathy has developed, the prognosis is determined largely by other markers of liver failure, such as the levels of albumin (a protein produced by the liver), the prothrombin time (a test of coagulation, which relies on proteins produced in the liver), the presence of ascites and the level of bilirubin (a breakdown product of hemoglobin which is conjugated and excreted by the liver). together with the severity of encephalopathy, these markers have been incorporated into the child–pugh score; this score determines the one- and two-year survival and may assist in a decision to offer liver transplantation. in acute liver failure, the development of severe encephalopathy strongly predicts short-term mortality and is almost as important as the nature of the underlying cause of the liver failure in determining the prognosis. historically, widely used criteria for offering liver transplantation, such as king's college criteria, are of limited use and recent guidelines discourage excessive reliance on these criteria. the occurrence of hepatic encephalopathy in people with wilson's disease (hereditary copper accumulation) and mushroom poisoning indicates an urgent need for a liver transplant. history the occurrence of disturbed behaviour in people with jaundice may have been described in antiquity by hippocrates of cos (c. 460–370 bce). celsus and galen (first and third century respectively) both recognised the condition. many modern descriptions of the link between liver disease and neuropsychiatric symptoms were made in the eighteenth and nineteenth century; for instance, giovanni battista morgagni (1682–1771) reported in 1761 that it was a progressive condition. in the 1950s, several reports enumerated the numerous abnormalities reported previously, and confirmed the previously enunciated theory that metabolic impairment and portosystemic shunting are the underlying mechanisms behind hepatic encephalopathy, and that the nitrogen-rich compounds originate from the intestine. professor dame sheila sherlock (1918–2001) performed many of these studies at the royal postgraduate medical school in london and subsequently at the royal free hospital. the same group investigated protein restriction and neomycin. the west haven classification was formulated by professor harold conn (1925–2011) and colleagues at yale university while investigating the therapeutic efficacy of lactulose.