Hepatic Encephalopathy

Chronic liver disease and cirrhosis affect hundreds of millions of patients all over the world. The majority of patients with cirrhosis will eventually develop complications related to portal hypertension. One of these recurrent and difficult to treat complications is hepatic encephalopathy. Studies have indicated that overt hepatic encephalopathy affects 30 to 45% of patients with cirrhosis and a higher percentage may be affected by minimal degree of encephalopathy. All of these factors add to the impact of hepatic encephalopathy on the healthcare system and presents a major challenge to the gastroenterologist, hospitalist and primary care physician.     

Hepatic Encephalopathy

1. Acute Encephalopathy in Cirrhosis A. GENERAL MEASURES. Tracheal intubation in patients with deep encephalopathy should be considered. A nasogastric tube is placed for patients in deep encephalopathy. Avoid sedatives whenever possible. Correction of the precipitating factor is the most important measure. B. SPECIFIC MEASURES i. Nutrition. In case of deep encephalopathy, oral intake is withheld for 24-48 h and i.v. glucose is provided until improvement. Enteral nutrition can be started if the patient appears unable to eat after this period. Protein intake begins at a dose of 0.5 g/kg/day, with progressive increase to 1-1.5 g/kg/day. ii. Lactulose is administered via enema or nasogastric tube in deep encephalopathy. The oral route is optimized by dosing every hour until stool evacuation appears. Lactulose can be replaced by oral neomycin. iii. Flumazenil may be used in selected cases of suspected benzodiazepine use. 2. Chronic Encephalopathy in Cirrhosis i. Avoidance and prevention of precipitating factors, including the institution of prophylactic measures. ii. Nutrition. Improve protein intake by feeding dairy products and vegetable-based diets. Oral branched-chain amino acids can be considered for individuals intolerant of all protein. iii. Lactulose. Dosing aims at two to three soft bowel movements per day. Antibiotics are reserved for patients who respond poorly to disaccharides or who do not exhibit diarrhea or acidification of the stool. Chronic antibiotic use (neomycin, metronidazole) requires careful renal, neurological, and/or otological monitoring. iv. Refer for liver transplantation in appropriate candidates. For problematic encephalopathy (nonresponsive to therapy), consider imaging of splanchnic vessels to identify large spontaneous portal-systemic shunts potentially amenable to radiological occlusion. In addition, consider the combination of lactulose and neomycin, addition of oral zinc, and invasive approaches, such as occlusion of TIPS or surgical shunts, if present. Minimal or Subclinical Encephalopathy Treatment can be instituted in selected cases. The most characteristic neuropsychological deficits in patients with cirrhosis are in motor and attentional skills (60). Although these may impact the ability to perform daily activities, many subjects can compensate for these defects. Recent studies suggest a small but significant impact of these abnormalities on patients' quality of life (61), including difficulties with sleep (62). In patients with significant deficits or complaints, a therapeutic program based on dietary manipulations and/or nonabsorbable disaccharides may be tried. Benzodiazepines should not be used for patients with sleep difficulties.     

Movement Dysfunction and Hepatic Encephalopathy

Hepatic encephalopathy is characterized by a variety of neurological symptoms. The occurrence of movement disorders is exceptional and is usually part of a clinical syndrome called acquired hepatocerebral degeneration, which is a subtype of chronic recurrent hepatic encephalopathy. The clinical picture is usually progressive and pathologic findings include regional astroglial and neuronal abnormalities found predominantly in cortex and basal ganglia. As for hepatic encephalopathy in general, the pathophysiology of this disorder is unknown but hyperammonemia and/or brain manganese overload may play a role. Medical treatment is often disappointing but in selected cases liver transplantation may be curative.     

乳果糖对临床及亚临床肝性脑病预防作用的实验研究

探讨乳果糖对临床肝性脑病（HE）及亚临床肝性脑病（SHE）的预防作用。方法：实验组和对照组新西兰家兔各8只,于实验前行体感诱发电位（SEP）,脑干听觉诱发电位（BAEP）和动脉血氨水平检查,于0及24时经耳静脉注射肝毒性药物,并从实验开始起分别喂饲乳果糖和葡萄糖（８h1次）作为HE／SHE的预防性用药,待出现肝功能衰竭后复查SEP、BAEP和动脉血氨水平,结果：出现肝功能衰竭后,实验组家兔SEPN波潜伏期和BAEPIII波,IV波潜伏期及I－IIII、I－IV峰间期较对照组缩短,动脉血氨明显下降,结论：乳果糖在急性肝功能衰竭的发生,发展过程中可以起到预防及减轻HE／SHE的作用。     

Blood Ammonia Levels and Hepatic Encephalopathy

The importance of measurements of the blood ammonia concentration in the evaluation of patients with known or suspected hepatic encephalopathy (HE) is still disputed in spite of a general acknowledgment that ammonia is important in the pathogenesis of the disorder. Several recent studies have suggested that it is not necessary to utilize arterial blood when measuring ammonia in the blood. Venous blood or a computation of the partial pressure of ammonia gas in blood samples may suffice. The value of blood ammonia measurements is limited by the fact that this is not the variable that is the most important. Ideally, one would like to know how much ammonia enters the brain, not how much is in the blood. The blood-brain barrier (BBB) is the critical and poorly understood element in this relationship. Although both ammonia in the gas and ionic forms cross the BBB, the ease with which this movement occurs is significantly higher in patients with HE. In the absence of simple methods to measure the brain ammonia metabolic rate and to assess the BBB to ammonia in conjunction with measuring the blood ammonia concentration, the variables that would be the most desirable to measure, the use of arterial and/or venous blood measurements needs to be coupled with a complete understanding of the physiology of cerebral ammonia metabolism.