Short-term oral zinc supplementation does not improve chronic hepatic encephalopathy. Results of a double-blind crossover trial.

The effect of short-term oral zinc supplementation (zinc sulfate 600 mg/day) on hepatic encephalopathy, was assessed in a double-blind, crossover trial. Fifteen cirrhotic patients with stable, chronic hepatic encephalopathy were randomized to receive either oral zinc or a placebo for 10 days. Following a two-week washout period, these were crossed over to the alternate treatment. Conn's index, which comprises the evaluation of the mental state, asterixis, number connection test, EEG record, and plasma ammonia, was used to score the degree of hepatic encephalopathy, both at the beginning and end of each treatment period. Serum zinc was significantly raised after oral zinc administration and reached the levels observed in cirrhotics without hepatic encephalopathy. Despite this, however, no modification in the parameters included in Conn's index were observed. In conclusion, this study failed to confirm that short-term oral zinc supplementation improves chronic hepatic encephalopathy.

Impaired hepatic handling and processing of lysophosphatidylcholine in rats with liver cirrhosis.

Lysophosphatidylcholine is a major metabolic product in the plasma and cellular turnover of phospholipids, with well-known membrane-toxic and proinflammatory properties. Because the liver plays a key role in plasma lysophosphatidylcholine removal and biotransformation and because virtually nothing is known of these processes in a diseased organ, the hepatobiliary metabolism of lysophosphatidylcholine was investigated in rats with carbon tetrachloride-induced liver cirrhosis. Twelve adult male Wistar rats with histologically confirmed cirrhosis and 8 control animals were fitted with jugular and biliary catheters and allowed to recover. The animals were kept under constant IV infusion of taurocholate (1 mumol/min). Two microcuries of sn-1[14C]palmitoyl-lysophosphatidylcholine was administered as a single bolus. The fate of the injected radioactivity, including removal from plasma, uptake, and subcellular location in the liver and molecular and aggregative forms, was studied by combined chromatographic and radiochemical methods. Major findings were (a) that lysophosphatidylcholine has a prolonged permanence in plasma of cirrhotic rats, due both to decreased hepatic clearance and to depressed conversion into phosphatidylcholine; (b) that the rate of lysophosphatidylcholine acylation is much slower in the cirrhotic than in the normal liver, both at the microsomal and at the cytosolic level; (c) that cytosolic lysophosphatidylcholine in the cirrhotic liver, but not in the normal liver, is predominantly non-protein bound; (d) that the strict molecular selectivity of lysophosphatidylcholine acylation observed in controls is partially lost in cirrhosis; and (e) that a consistent fraction of lysophosphatidylcholine is converted into triacylglycerols in cirrhotics but not in controls. These findings show a profound derangment of lysophosphatidylcholine handling and processing in the cirrhotic liver, which is of potential pathogenetic significance.

Lactitol in the treatment of chronic hepatic encephalopathy--a randomized cross-over comparison with lactulose.

The effect of lactitol, a new non-absorbable disaccharide, in the treatment of chronic hepatic encephalopathy was assessed in 14 cirrhotic patients with non-selective portosystemic anastomosis in a randomized, cross-over study. At the time of inclusion, all patients showed alterations in mental state, and/or psychometric performance, and in the electroencephalogram. Moreover, 10 out of 14 patients suffered from recurrent episodes of hepatic encephalopathy in the 12 months prior to the study. Patients were randomly treated for two consecutive periods of six months with either lactitol or lactulose. The PSE index was calculated to quantify the neuro-psychiatric impairment. Twelve patients completed the study. The patients required a daily dose of 38.2 g +/- 19 of lactulose or 36.3 g +/- 5 of lactitol to produce two semi-soft stools per day. No deterioration in the mental state or in the other neuro-psychiatric parameters were observed, neither during lactitol nor during lactulose therapy. During the study, mild episodes of recurrent encephalopathy occurred in 60% of the patients taking lactulose, and in 25% of the patients taking lactitol, the difference not being significant (X = 1.54, p = 0.21). Flatulence, the major side-effect noted during the study, was present in 7 of the 12 patients during lactulose treatment, and in 2 patients during lactitol treatment; one patient on lactitol complained of nausea. The side effects which occurred during lactitol of the dosage, while those occurring during lactitol appeared when the dosage was higher than 40 g. Lactitol may be considered at least as effective as lactulose in the treatment of chronic hepatic encephalopathy.

Basal energy production rate and substrate use in stable cirrhotic patients.

The basal energy production rate was measured using indirect calorimetry in 25 stable cirrhotic patients and 10 controls of comparable age. The endogenous substrate oxidation was also calculated by measuring urinary nitrogen excretion. The energy production rate was similar in cirrhotic patients and controls. The origins of liver disease and the degree of liver damage did not seem to influence the energy production rate. On the other hand, in cirrhotic patients, as in controls, a significant correlation was present between the energy production rate and parameters of body size, such as body weight and fat-free mass. As a consequence, cirrhotic patients with poor nutritional status, with a reduced fat-free mass, showed a lower energy production rate. The measured energy production rate was compared with the resting energy expenditure estimated by formulas commonly used in healthy individuals. The good agreement found between the measured energy production rate and calculated energy expenditure suggests that these formulas may be applied to stable cirrhotic patients in clinical practice. In cirrhotic patients, the oxidation of endogenous fat is the main contributor to basal energy production rate. The fat oxidation rate does not appear to be influenced by the hormonal pattern found in the cirrhotic patients. However, a significant correlation was present between fat oxidation and plasma free fatty acid levels. This confirms that the prevalent fat use in cirrhotic patients is supported by the greater availability of fat-derived substrates.

Lactitol in prevention of recurrent episodes of hepatic encephalopathy in cirrhotic patients with portal-systemic shunt.

Recurrent episodes of hepatic encephalopathy (HE) frequently occur in surgically shunted cirrhotic patients. The prevention of these episodes is based mainly on the long-term use of lactulose. Recently, lactitol, a nonabsorbable disaccharide similar to lactulose, has been proposed as an alternative in the management of HE. It has the advantage of being better tolerated and producing a more predictable catharsis. The effects of the two agents were compared in a controlled randomized study lasting six months involving 31 cirrhotic patients with portal-systemic shunt, of whom 40% experienced HE. The PSE index (mental state, EEG, asterixis, Raitan test, and ammonia) was assessed in each patient on entry to the study and every three months during treatment. Episodes of HE, side effects, and the patients' comments on efficacy, tolerability, and palatability were recorded. The dose required to induce two bowel movements per day was 48 +/- 25 ml of lactulose syrup and 36 +/- 7 g of lactitol. During the study, the number of patients who had an episode of HE and the PSE index was similar in both groups. The patients judged lactitol better from the point of view of palatability. Meteorism and flatulence, experienced by patients treated with lactulose, was not reported by the lactitol group. We concluded that lactitol is as effective as lactulose in the long-term prevention of episodes of HE in cirrhotics with portal-systemic shunt and may be better tolerated.

Carbon tetrachloride-induced experimental cirrhosis in the rat: a reappraisal of the model.

The goal of this study was to evaluate the presence of extrahepatic damage and the uniformity and reversibility of the histological findings in CCl4-induced liver cirrhosis in the rat. To verify these findings rats were sacrificed 2 and 10 weeks after a treatment consisting of ten intragastric doses of CCl4, administered weekly. All treated rats developed an irreversible micronodular cirrhosis with no damage to the brain, kidney and pancreas. Moreover, rats sacrificed 2 weeks after the last CCl4 dose showed a number of functional alterations usually observed in man. In particular, low branched chain/aromatic amino acids (BCAA/AAA) plasma ratio, high ammonia, low zinc and high insulin with normal blood glucose were obtained.