Hepatic encephalopathy in cirrhotic

Infection, gastrointestinal bleeding or injudicious use of sedatives and diuretics can precipitate hepatic encephalopathy in cirrhotic patients. The pathophysiology is complex but ammonia appears to hold a central role. Derived mainly from the action of colonic urease-containing bacteria, ammonia is... 

Cadranel, J.-F., Lebiez, E., di Martino, V., Bernard, B., H Koury, S., Tourbah, A., Pidoux, B., Valla, D., Opolon, P. Focal neurological signs in hepatic encephalopathy in cirrhotic patients an underestimated entity Amer. X. Gastroenterol. 2001 96 515-518... 

Marchesini, G., Zoli, M., Dondi, C., Cecchini, L., Angiolini, A., Bian-chi, F.B., Pisi, E. Prevalence of subclinical hepatic encephalopathy in cirrhotics and relationship to plasma amino acid imbalance. Dig. Dis. Sci. 1980 25 763-768... 

Sood, G.K., Sarin, S.K., Mahaptra, J., Broor, S.L. Comparative efficacy of psychometric tests in detection of subclinical hepatic encephalopathy in nonalcoholic cirrhotics search for a rational approach. Amer. J. Gastroenterol. 1989 84 156-159... 

Scotinoitis, LA., Lucey, M.R., Metz, D.C. Helicobacter pylori infection is not associated with sut linical hepatic encephalopathy in stable cirrhotic patients. Dig. Dis. Sci. 2001 46 2744-2751... 

Lavoie J, Pomier Layrargues G, Butterworth RF Increased densities of peripheral-type benzodiazepine receptors in brain autopsy samples from cirrhotic patients with hepatic encephalopathy. Hepatology 1990 11 874-882. 

It is important to note that, even more than in heart failure, overly aggressive use of diuretics in this setting can be disastrous. Vigorous diuretic therapy can cause marked depletion of intravascular volume, hypokalemia, and metabolic alkalosis. Hepatorenal syndrome and hepatic encephalopathy are the unfortunate consequences of excessive diuretic use in the cirrhotic patient. 

Drugs that can disturb fluid-electrolyte balance must be used with caution in patients with certain types of liver impairment. Diuretics, for example, are often required to treat ascites but can cause hypo-natraemia, hypo- or hyperkalaemia. A disturbance in electrolyte balance can lead to encephalopathy in susceptible patients such as cirrhotics or those with acute liver failure. Dehydration induced by diuretics is a common precipitant of hepatic encephalopathy. The mechanism is not fully understood, but could possibly be due to the reduced metabolism of hepatic toxins because of hepatic hypoxia [5]. 

L-dopa, a precursor of the neurotransmitters norepinephrine and dopamine, was introduced into HE therapy by J.D. Parkes et al. in 1970. The results were good. As yet, there is still no accepted opinion on the use of this substance. Piracetam, as a nootropic substance, led to a clear improvement in typical electrical brain activities in animals displaying hepatic damage and symptoms of encephalopathy. Similarly, a double-blind randomized cross-over study with the nootropic agent centropheno-xine partly showed positive effects in psychometric testing. Bromocriptine, an agonist of the dopamine receptor, was also used in 1980 for chronic hepatic encephalopathy. (146,163) Application of L-carnitine (6 g/day orally, divided into two doses, for 4 weeks) leads to a marked reduction of hyperammonaemia and a clear improvement in clinical symptoms of HE in cirrhotic patients. (119) (s. p.49)... 

Giiven, K., Kelestimur, F., Yiicesoy, M. Thyroid function tests in nonalcoholic cirrhotic patients with hepatic encephalopathy. Eur. X Med. 1993 2 83-85... 

Higuchi, K., Shimizu, Y., Nambu, S., Miyabayashi, C., Takahara, T., Saito, S., Hioki, O., Kuwabara, Y., Watanabe, A. Effects of an infusion of branched-chain amino acids on neurophysiological and psychometric testings in cirrhotic patients with mild hepatic encephalopathy. 

McClain, C.J., Potter, T.J., Kromhout, J.R, Zieve, L. The effect of lactulose on psychomotor performance tests in alcoholic cirrhotics without overt hepatic encephalopathy. J. Clin. Gastroenterol. 1984 6 325-329... 

Watanabe, A., Sakai, T., Sato, S., Imai, F., Ohio, M., Arakawa, Y., Tod G., KobayasU, K., Muto, Y., Tsujii, T., Kawasaki, H., Okita, K., Tanikawa, K., Fujiyama, S., Shimada, S. Clinical efficacy of lactulose in cirrhotic patients with and without subclinical hepatic encephalopathy. Hepatology 1997 26 1410-1414... 

In liver cirrhosis, hepatorenal syndrome is nearly always (> 80%) accompanied by ascites. HRS is most common in alcoholic cirrhosis. In some 75% of cases, hepatic encephalopathy is witnessed at the same time, and jaundice is evident in about 40% of cases. HRS occurred in 18% of all cirrhotic patients with ascites within one year and in 32% within 5 years. (21)... 

Shibasaki K, Tsuboi Y, Hasegawa K, Toshima M, Soga K. Effects of long-term administration of lactitol or lactulose in cirrhotic patients with chronic hepatic encephalopathy. Ther Res 2001 22 899-907. 

Because the hver metabohzes the aromatic amino acids (i.e., phenylalanine, tyrosine, and tryptophan), methionine, and glutamine, the plasma concentrations of these amino acids are elevated in cirrhotic patients. Plasma concentrations of the branched-chain amino acids (BCAAs) (i.e., valine, leucine, and isoleucine) often are depressed because these amino acids are metabohzed by skeletal muscle. This altered plasma aminogram contributes to the development of hepatic encephalopathy. 

Mousseau DD, Pomier Layrargues G, Butterworth RF. Region-selective decreases in densities of pH]-tryptamine binding sites in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. J. Neurochem., 61, 621-625, 1994 Mousseau DD, Baker GB, Butterworth RF. Increased density of catalytic sites and expression of brain monoamine oxidase A in humans with hepatic encephalopathy. J. Neurochem., 68, 1200-1208,1997... 

Also in contrast to cirrhotics and patients with porto-systemic bypass without hepato-cellular disease, altered mental status in patients with acute liver failure may be due to the presence of seizure activity or hypoglycemia. A status of complex partial seizures may be misinterpreted as bizarre behaviour in the course of acute hepatic encephalopathy. Seizures may even continue under neuroleptanalgesia, and then cannot be detected by clinical observation. 

Rare complications of liver cirrhosis are chronic persistent hepatic encephalopathy and hepatic myelopathy. Both occur in less than 1% of the patients, and both are accompanied by extensive porto-systemic shunts. Chronic persistent hepatic encephalopathy is also known as acquired hepato-lenticular degeneration (Victor, Adams and Cole, 1965). In contrast to the nsnal cirrhotic patient with HE, these patients show obvions neuronal alterations a patchy, spongy degeneration most consistently observed in the deep layers of the cerebral cortex and subcortical white matter, particularly in the parieto-occipital cortex, basal ganglia and cerebellum. 

As hyperammonemia is considered to be the main cause of hepatic encephalopathy, specific therapy for HE is aimed at the reduction of anunonia production and resorption. Protein restriction has been recommended for a long time to reduce ammonia production. But patients with cirrhosis are hypercatabolic. They may require up to 1.5 g/kg protein per day. Therefore protein restriction has been limited to patients with severe hepatic encephalopathy, and a reduction to less than 1 g protein per kg body weight has been discouraged in the past. A recent clinical study even showed no benefits of protein restriction (Cordoba et al., 2004). 30 cirrhotics who were admitted to the hospital with hepatic encephalopathy were randomized to a low-protein diet or normal protein diet. After two weeks of treatment, the groups did not significantly differ with regard to the course of hepatic encephalopathy. 

Schomerus, H., Hamster, W. 2001. Quality of life in cirrhotics with minimal hepatic encephalopathy. Metab Brain 16 (1/2) 37-42... 

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