Portosystemic encephalopathy

Di Piazza S, Filippazzo GM, Valenza LM, Morello S, Pastore L, Conti A, Cottone S, Pagliaro L Rifaximin versus neomycin in the treatment of portosystemic encephalopathy. ItalJ Gastroenterol 1991 23 403-407. 

TABLE 21-6 Portosystemic Encephalopathy Precipitating Factors and Therapy... 

Kiigler, Ch. F.A., Lotterer, E., Fetter, J., Wensing, G., Ahmad Taghary, Hahn, E.G., Fleig, W.E. Visual event-related P 300 potentials in early portosystemic encephalopathy. Gastroenterology 1992 103 302-310... 

Such terms as hepatargy , leucoencephalopathy , shunt encephalomyelopathy and encephalomyelo-pathy were put forward to classify these central nervous disorders. The term portosystemic encephalopathy... 

The expression hepatic encephalopathy (HE) is a collective term covering five clinical forms of disease (H.O. Conn, 1989) (7.) Reyc s syndrome, (2.) enzyme deficiency of the urea cycle, (i.) pseudoportosystemic encephalopathy, (4.) fulminant liver failure, and (J.) portosystemic encephalopathy. It is not known whether the pathogenic mechanisms of these various clinical forms are identical, (s. tab. 15.3)... 

Portosystemic encephalopathy (PSE) develops in chronic liver diseases and/or in the wake of portosystemic circulation. Liver cirrhosis with its hepatofugal collateral circulatory pathway is thus the focus of interest in this clinical form of disease. The term PSE is identical to exogenous liver coma or liver cell failure coma . PSE can be further subdivided according to its symptomatology and depending on its form and degree of severity. There are three forms of portosystemic encephalopathy (1.) subclinical (or latent) PSE, (2.) acute or acute recurrent (episodic) PSE, and (i.) chronic recurrent or chronic persistent PSE. 

The acute or acute recurrent form can be equated with the manifestation of portosystemic encephalopathy in chronic liver disease. It is also known as acute episodic form . Discrete psychometric disorders usually precede the manifest picture as a latent stage. Manifestation includes stages I-IV and hence covers a wide spectrum of clinical, neurological and psychopathological symptoms. Once the liver function is stabilized and the trigger factors are eliminated, all the symptoms of this form are as a rule reversible. 

Sanyal, A.J., Freedman, A.M., Shiffman, M.L., Purdum, PR, Luketic, V.A., Cheatham, A.K. Portosystemic encephalopathy after transjugular intrahepatic portosystemic shunt results of a prospective controlled study. Hepatology 1994 20 46-55... 

Schomerus, H., Hamster, W., Blunck, H., Reinhard, U., Mayer, K., Dolle, W. Latent portosystemic encephalopathy. I. Nature of cerebral functional defects and their effect on fitness to drive. Dig. Dis. Sci. 1981 26 622-630... 

Plauth, M., Egberts, E.-H., Hamster, W., Torok, M., MuBer, P.H., Brand, O., Flirst, R, Dolle, W. Long-term treatment of latent portosystemic encephalopathy with branched-chain amino acids. A doubleblind placebo-controlled crossover study. X Hepatol. 1993 17 308-314... 

When oral intake is precluded, the recommended daily parenteral supplementation of manganese is 0.15-0.8 mg. Manganese is mainly excreted in the bile during cholestasis serum manganese levels may rise, and manganese toxicity can result. Hjq)ermanganesemia after parenteral nutrition when first reported was linked to portosystemic encephalopathy. Patients with liver disease were particularly at risk. 

In patients with diabetes plus liver cirrhosis, acarbose treatment appears to be favourable because it improves the detoxification of ammonia (Muting, 1984). Acarbose induces an increased growth of lactobacteria, lowers intestinal pH and hyperammonaemia, inducing a beneficial effect on portosystemic encephalopathy. It also reduces lipolysis and ketogenesis in cirrhotic patients (Zillikens et at., 1989), following a late evening meal with 100 mg acarbose. 

Portal hypertension most commonly occurs as a consequence of chronic liver disease. Portal hypertension Is caused by Increased blood flow within the portal venous system and increased resistance to portal flow within the liver. Splanchnic blood flow is increased in patients with cirrhosis due to low arteriolar resistance that is mediated by increased circulating vasodilators and decreased vascular sensitivity to vasoconstrictors. Intrahepatic vascular resistance is increased in cirrhosis due to fixed fibrosis within the spaces of Disse and hepatic veins as well as reversible vasoconstriction of hepatic sinusoids and venules. Among the consequences of portal hypertension are ascites, hepatic encephalopathy, and the development of portosystemic collaterals—especially gastric or esophageal varices. Varices can rupture, leading to massive upper gastrointestinal bleeding. 

There are several theories behind the cause of hepatic encephalopathy. One of these is that the accumulation of toxins in the brain, particularly ammonia, is the cause. Ammonia is produced in the intestine and is usually metabolised in the liver to urea via the urea cycle. As a result of portosystemic shunting and reduced metabolism in the liver, ammonia serum levels rise as the transformation to urea is reduced. However, the validity of this theory is questionable as not all patients with signs of hepatic encephalopathy have raised serum ammonia levels. Another theory is that patients with hepatic encephalopathy have increased permeability of the blood-brain barrier, and hence the increased toxin levels permeate the brain more than usual, leading to altered neuropsychiatric function. There are also theories relating to increased levels of neurotransmitters, short-chain fatty acids, manganese and increased GABA-ergic transmission. 

There can be a pronounced increase in methionine and its derivatives in acute liver failure or in serious cases of cirrhosis. From these substances, mercaptans are formed in the colon (e. g. methandiol, ethandiol, dimethyldisul-phide). The cause of the sweetish aromatic smell of the expiratory air ( fresh-raw liver ) known as hepatic foetor (F. Umber, 1926 L. Schiff, 1946) is deemed to be volatile dimethylsulphide. (38) Its concentration does not correlate with the degree of encephalopathy or hepatic insufficiency, but with the intensity of the portosystemic shunts. Trimethylamine is also suspected of being a causative factor. (22) (s.pp 267, 379)... 

The occurrence of hepatic encephalopathy (HE) is only possible under the following conditions (1.) a serious (acute or chronic) liver disease, in which the detoxification function is significantly restricted, has to be present, and/or (2.) a functional or anatomic portosystemic collateral circulation must exist — this can be placed surgically or in the form of a TIPS (72, 90) -through which the nondetoxified portal blood bypasses the liver, so that toxic substances can reach the brain. 

While hepatic encephalopathy is nearly always found in acute liver failure, it can only be expected in some 25-40% of patients with a portosystemic shunt. When these two preconditions coincide, as in the case of liver cirrhosis, manifest hepatic encephalopathy is witnessed in 30-50% of patients and a subclinical course of disease in 50-70%. In other words, the frequency, the degree of severity and the course taken by HE depend on the underlying conditions. 

Sarin, S.K., Nundy, S. Subclinical encephalopathy after portosystemic shunts in patients with non-cirrhotic portal fibrosis. Liver 1985 5 142-146... 

As implied by the synonym, chronic hepatic encephalopathy occurs in the setting of portosystemic shunting, usually as a result of cirrhosis. 

The major aims of interventional procedures for portal hypertension are prophylactic and emergent treatment of variceal bleeding, control of hepatic encephalopathy, and treatment of refractory ascites. Hypersplenism associated with hematological disorder is an additional clinical problem in patients with portal hypertension. At present, the main primary embolotherapies available for portal hypertension are balloon-occluded retrograde transvenous obliteration (BRTO) and partial splenic embolization (PSE). In Japan, BRTO has recently been applied for gastric varices instead of either endoscopic treatment or transhepatic intrahepatic portosystemic shunt (TIPS) procedure, and numerous studies have reported that this method has an excellent success rate. Its efficacy for control of hepatic encephalopathy has also been demonstrated. 

A57-year-old man taking VPA 1000 mg/day developed hyperammonemic encephalopathy and subsequent coma. He had portal hypertension secondary to history of alcohol abuse and was found to have a portosystemic shxmt, which had previously gone xiimoticed. While asymptomatic hyperammonemia is a relatively common side effect of VPA, encephalopathy and coma are less common. The portosystemic shunt may have prevented metabolism of ammonia in this case [185 ]. Regardless, VPA should be used with caution in a patient with a history of alcohol abuse given the increased risk for liver disease. 

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