Chronic hepatic coma

In endogenous hepatic coma (= due to loss of liver parenchyma), which in most cases develops from an existing chronic liver disease ( acute on chronic ), the prognosis is better than for acute liver failure, but nevertheless remains extremely poor. According to the information available in the relevant literature, 10-20% of patients die in stage I and 40-50% in stage II in stages III and IV, lethality is 80-90%, the same rate as in acute liver failure, (see chapter 20)... 

Cabre, E., Periago, J.L., Gonzalez, J., Gonzalez-Huix, F., Abad-Lacruz, A., Gil, A., Sancbez-Medina, F., Esteve- Comas, M., Fernandez-Ban-ares, F., Planas, R., Gassull, M.A. Plasma polyunsaturated fatty acids in liver cirrhosis with or without chronic hepatic encephalopathy a preliminary study. X. Parenter. Enter. Nutr. 1992 16 359-363... 

In the course of acute or chronic liver disease, the biochemical functions of the liver may be compromised indefinitely the outcome is decompensated liver insufficiency. (s. pp 277, 381) (s. tab. 20.4) The stage of decompensation is synonymous with the onset of life-threatening complications. These mainly take the form of hepatic encephalopathy with transition to hepatic coma (see chapter 15), oedema and ascites with imbalance of the electrolytes and the acid-base equilibrium (see chapter 16) through to the hepatorenal syndrome (see chapter... 

Chapter 6 reviewed tryptophan and toxic liver disease. This section deals with the effects or influences of tryptophan on chronic liver disease in association with hepatic coma. Chronic liver disease in humans is often associ-... 

Paromomycin, an aminoglycoside with antibacterial and amebicidal properties, is indicated in the treatment of acute and chronic intestinal amebiasis, of tapeworm (fish, beef, pork, and dog) infections in patients who cannot take praziquantel or niclosamide, and as an adjunctive regimen in the management of hepatic coma. 

Fig. 9.1 Alzheimer Type II astrocytosis in HE (chronic liver failure) (a) light micrograph of cerebral cortex from a cirrhotic patient who died in hepatic coma. Note prominence of pale, enlarged astroglial nuclei frequently occurring in pairs (anvw) suggestive of hyperplasia. A normal astrocyte nucleus is shown for comparison purposes (arrowhead). Bar = 20 pM. (b) Similar section showing intranuclear glycogen inclusions (arrow). Inset irregular lobular astrocyte in pallidum. Reproduced from Norenbeig (1987), with permission from Humana Press...

Table 9.2 Brain manganese concentrations in dissected pallidal tissue from drrhotic patients who died in hepatic coma and from rats with experimental acute or chronic hver failure...

There is evidence to suggest that changes in expression of the PTBR are an integral part of the Alzheimer type II changes that are characteristic of astrocytes in chronic liver failure (Fig. 9.1). Expression of the PTBR IBP is significantly correlated with the presence of Alzheimer type II changes in autopsied brain tissue from cirrhotic patients who died in hepatic coma (Belanger et al., 2004). 

Other neuroactive and neurotoxic metabohtes of tryptophan are also reportedly increased in the brain with chronic hver failure. One such example is quinolinic acid (QUIN) synthesized from tryptophan via the kynurenine pathway. QUIN synthesis is particularly sensitive to increased availability of tryptophan. QUIN has been identified in both rodent and human brain extracts and cerebral cortical QUIN concentrations are elevated in rats following portacaval anastomosis (Moroni et al., 1986a). Eurthermore, QUIN concentrations are increased up to sevenfold in CSF and autopsied frontal cortex of cirrhotic patients who died in hepatic coma (Moroni et al., 1986b). 

The relationship between drug concentration and response also can be altered in patients with advanced liver disease. Of greatest concern is the fact that customary doses of sedatives may precipitate the disorientation and coma that are characteristic of portal-systemic or hepatic encephalopathy. Experimental hepatic encephalopathy is associated with increased y-aminobutyric acid-mediated inhibitory neurotransmission, and there has been some success in using the benzodiazepine antagonist flumazenil to reverse this syndrome (50). This provides a theoretical basis for the finding that brain hypersensitivity, as well as impaired drug elimination, is responsible for the exaggerated sedative response to diazepam that is exhibited by some patients with chronic liver disease (51). Bakti et al. (52) conducted a particularly well-controlled... 

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