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Lactitol versus lactulose in the treatment of acute portal systemic encephalopathy (PSE). A controlled trial.

Preliminary data suggest that lactitol (beta-galactoside-sorbitol), a new synthetic non-absorbable disaccharide, has beneficial effects on chronic portal systemic encephalopathy. To compare the efficacy of lactitol vs. lactulose in the treatment of acute portal systemic encephalopathy (PSE), 40 cirrhotic patients with an acute episode of PSE were randomly allocated to one of two groups: group A (20 patients) received lactulose (30 ml/6 h) and group B (20 patients) lactitol (12 g/6 h). These doses were adjusted daily to obtain two bowel movements per day. The duration of treatment was 5 days. Age, sex, hepatic and renal function, precipitating factors and level of PSE measured by clinical examination, EEG and number connection test were similar in the two groups. A complete clinical resolution of PSE occurred in 11 patients in each group. In 5 patients of the lactulose group and in 6 of the lactitol group there was a moderate improvement of PSE during the study. Finally, 4 patients in the lactulose group and 3 in the lactitol group did not respond to treatment. No side effects attributable to therapy were observed in either group. These results indicate that lactitol is as effective as lactulose in the management of patients with cirrhosis and acute PSE.

Acute Disease↗

Role of spontaneous portal-systemic shunting in hyperinsulinism of cirrhosis.

The possible contribution of hepatocellular damage and portal-systemic shunting to hyperinsulinism in cirrhosis was studied in 23 cirrhotics, 8 of whom had a surgical portacaval shunt, and 16 controls by measuring insulin and the connecting peptide (C-peptide) concentrations in simultaneous samples of peripheral arterial and hepatic venous blood. The fractional hepatic insulin extraction (0.48 +/- 0.06, mean +/- SE) was normal in cirrhosis. The hepatic insulin elimination rate was directly related to arterial insulin levels (r = 0.91, P less than 0.001) even at very high circulating levels. Extrahepatic insulin metabolism was measured across the kidney and lower limb. There were no significant differences between cirrhotics and control subjects in relation to renal (0.25 +/- 0.05 vs. 0.23 +/- 0.04) and lower limb insulin extraction (0.14 +/- 0.07 vs. 0.19 +/- 0.04). While in the control group hepatic venous insulin (0.143 +/- 0.018 pmol/ml) markedly exceeded the peripheral insulin concentration (0.083 +/- 0.009 pmol/ml, P less than 0.01), the contrary was found in cirrhotics with end-to-side portacaval shunt in whom all the pancreatic venous effluent is shunted to the systemic circulation (hepatic venous insulin, 0.130 +/- 0.028 pmol/ml; peripheral, 0.234 +/- 0.037 pmol/ml; P less than 0.01). Portal-hypertensive cirrhotics without a surgical portacaval shunt also had hepatic venous insulin levels (0.132 +/- 0.029 pmol/ml) below peripheral arterial insulin concentrations (0.205 +/- 0.041 pmol/ml, P less than 0.01). The study suggests that hyperinsulinism in cirrhosis is not the result of an intrinsic defect of hepatic insulin metabolism but of the spontaneous shunting of portal blood to the systemic circulation.

C-Peptide↗

Portal-systemic encephalopathy and hypothalamic hypothyroidism: effect of thyroid hormone on ammonia metabolism.

We describe a 53-year-old woman with portal-systemic encephalopathy and altered thyroid function. Endocrinological studies revealed low levels of free thyroid hormone with an inappropriately low level of thyroid-stimulating hormone that responded to bolus injection of thyrotropin-releasing hormone with a normal but somewhat delayed pattern. On the diagnosis of hypothalamic hypothyroidism, she was treated with levothyroxine sodium. Thyroid hormone replacement improved not only the symptoms of hypothyroidism but the hyperammonemia and consciousness disturbance, which suggested a hitherto undescribed possibility that hypothyroidism may be an exacerbation factor of hyperammonemia and portal-systemic encephalopathy.

Ammonia↗

[Electroencephalography and cerebrospinal fluid glutamine in portal-systemic encephalopathies].

A group of patients with portal-systemic encephalopathy were studied. The conscious disturbances, eletroencephalographic findings and the spinal fluid glutamine levels were analyzed. Based on the results the authors concluded that the eletrencephalogram can be utilized for determination of the degree of hepatic coma and also for its prognostic valuation. In addition they found that monitorization of spinal fluid glutamine levels is the most important test for characterization of the degree of hepatic encephalopathy.

Adult↗

Symptomatic portal system thrombosis in soldiers due to extended stay at extreme altitude.

BACKGROUND: With induction of Indian Army to heights over 5000 m above mean sealevel (MSL), several new complications of long-term stay at extreme altitude have come to light. The authors' experience with soldiers who developed symptomatic portal system thrombosis (SPST) is described here. METHODS: Clinical data were prospectively collected between April 1998 and April 2003, on all patients hospitalized for SPST from high-altitude areas (HAA, >3000 m above MSL) and those from non-high-altitude areas (NHAA). Site of thrombosis was confirmed by imaging and included splenic, portal, superior mesenteric, or inferior mesenteric vein thrombosis. Patients were investigated to rule out known predisposing factors and prothrombotic conditions. RESULTS: A total of 37 cases of SPST were seen during the study period, of which 26 were from HAA. Mean age of cases from HAA was 27 +/- 4.6 years and all were male. Mean stay at high altitude was 11.7 +/- 6.2 months. First symptom was pain in abdomen in almost all the cases, later followed by gastrointestinal bleeding and fever in 14 each, and vomiting in 19. Clinical examination showed ascites (81%), splenomegaly (76.9%), and hepatomegaly (69.2%). Diagnosis was made by imaging scans (23 cases) and on surgery in three cases. A known prothrombotic state was detected in five cases from HAA and in eight cases from NHAA (P < or = 0.01). Ultrasound Doppler scan picked up collaterals as early as 12-45 days after onset of symptoms. CONCLUSIONS: Extended stay at HAA may be a risk factor for development of symptomatic portal system thrombosis.

Adult↗

Amino acid sensors sensitive to alanine and leucine exist in the hepato-portal system in the rat.

We reported the existence of vagal arginine sensors in the liver which modulate arginine-induced pancreatic hormone secretion. The present study was carried out to examine the possible existence of other amino acid sensors such as L-alanine and L-leucine in the hepato-portal system in rats using an electrophysiological approach. Afferent discharges were recorded from fine filaments dissected from the peripheral cut end of the hepatic branch of the vagus nerve. Administration of 0.1, 1, and 10 mM L-alanine and L-leucine solution (0.1 ml) into the portal vein caused an increase in the discharge rate of hepatic vagal afferents in a dose-dependent manner. The results suggest the existence of vagal amino acid sensors which are sensitive to alanine and leucine in the hepato-portal system.

Alanine↗

Anatomical study of the renal portal system in the duck (Anas platyrhincos).

Sixteen healthy mature ducks of both sexes were used in the present study. The injection of a polymerizing material was made via the posterior vena cava and, after a complete corrosion, casts were obtained for the examination of the entire venal network of the kidneys. Similar injections were made in a limited number of fowls, in order to facilitate the comparison between our findings in the duck and those in the fowl. The renal portal system as well as the renal veins of the duck were identified and illustrated in detail. The anatomical relation of the renal portal system to the renal veins and to the coccygomesenteric vein was examined and evaluated. From the comparison of the findings in the duck and fowl, the main differences in the duck were found to be the following: the cranial portal vein was rudimentary, the distance between the two caudal portal veins as well as that between the two renal veins was short, the posterior part of the caudal renal portal vein and the renal vein were located superficially and ventrally to the caudal lobe of the kidney, and the distance between the caudal renal portal vein and the homolateral vein was also short.

Animals↗

Portal-systemic encephalopathy and gastrointestinal bleeding after cardioselective beta-blocker (metoprolol) administration to patients with portal hypertension.

The use of the non-selective beta-blocker propranolol has been widely recommended to prevent gastrointestinal bleeding in patients with portal hypertension. We conducted a prospective, randomized controlled trial of metoprolol, a selective beta-blocker for prevention of gastrointestinal bleeding from portal hypertension in 29 non-selected patients with liver disease and previous gastrointestinal bleeding. Fifteen patients received placebo treatment for 40 +/- 18 months and 14 patients received metoprolol for 31 +/- 17 months. A sustained reduction in resting pulse was observed in those patients treated with metoprolol. There was no significant difference in acute re-bleeding episodes between the two groups. Of the 14 patients treated with metoprolol, three (21%) re-bled, all three requiring blood transfusion. Four (26.5%) of the 15 patients treated with the placebo re-bled, two cases with acute bleeding and the remaining two cases presented a positive stool guaiac test. All cases who bled during the metoprolol therapy required exclusion from the trial, and surgical procedures or sclerotherapy as well. After both metoprolol or placebo treatments, similar deterioration of standard liver function tests was observed. Further, at the end of the trial, 11 patients on metoprolol (78%) and four of the patients treated with the placebo (27%) required treatment for clinical portal-systemic encephalopathy (p < 0.01). The risk of poor sympathomimetic response after cardioselective beta 1-blocker during acute bleeding episodes and the appearance of hepatic encephalopathy deserve further investigation. The selective beta-blocker metoprolol seems to be an inadequate choice to prevent gastrointestinal re-bleeding in patients with portal hypertension.

Adrenergic beta-Antagonists↗

Symptomatic hepatic disease in cystic fibrosis: incidence, course, and outcome of portal systemic hunting.

Fifteen (2.2%) of 693 patients with cystic fibrosis seen over an 18-year period developed clinical hepatic disease. In 13 patients all symptoms were secondary to portal hypertension. Ten had hypersplenism and 6 had variceal bleeding, including 3 who developed both conditions. All 5 patients who survived the initial episode of gastrointestinal bleeding underwent portal systemic shunting. A shunting procedure also was performed on 1 patients with hypersplenism but no variceal bleeding. No subsequent deterioration of intellectual function occurred in either the shunted or unshunted patients. Only 1 of the shunted patients showed progression of hepatic disease after surgery. These results suggest that portal systemic shunting is useful in the treatment of bleeding esophageal varices in cystic fibrosis. A sweat test to rule out cystic fibrosis should be included in the evaluation of any teenage or young adult patient with unexplained portal hypertension.

Adolescent↗

[Schistosoma mansoni: quantitative aspects of the development of irradiated cercariae in the skin, lungs and portal system, in mice].

The migration of Schistosoma mansoni (LE and SJ strains) has been studied in eight groups of outbred Swiss albino mice (Mus musculus), which were previously infected with ca 450 cercariae, transcutaneously. The infection of mice was performed with non irradiated cercariae (control groups), or with gamma-irradiated cercariae, at the schedule of 3, 20 and 40 Krad. Regarding the skin, a progressive decrease was detected for the recovery rates, related to the time of infection. As far as the lungs and portal system are concerned, a significant inverse correlation was observed between the total recovery rate and the irradiation dosages. The dose of 20 Krad practically hinders the migration of the parasites (in both strains) from the lungs to the portal system, whereas the dose of 40 Krad prevents the migration of most of the parasites from the skin to the lungs.

Animals↗

Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial.

A randomized double blind clinical comparison of neomycin and lactulose was performed in 33 cirrhotic patients with chronic portal-systemic encephalopathy (PSE) at seven cooperating hospitals. In order to maintain double blindness, sorbitol syrup was used as a control solution along with neomycin and was compared with lactulose syrup and placebo tablets in a double drug protocol. Twenty-nine patients were studied in a crossover investigation in which each received both therapeutic regimens preceded and followed by control periods. Four additional patients received one or the other agent, but did not receive both. Serial, semiquantitative assessments were made in all patients of mental status, asterixis, and the trailmaking test (TMT) and electroencephalograms (EEG) and arterial ammonia levels. Both neomycin-sorbitol and lactulose were effective in the majority of patients (83 and 90%, respectively). Each of these parameters (mental state, asterixis, TMT, EEG, and NH3) was improved significantly by neomycin-sorbitol and lactulose. The post-treatment levels for each of these measures were similar in the neomycin and lactulose-treated groups. Mean stool pH was reduced by neomycinsorbitol to 6.1 and by lactulose to 5.5. This difference was highly significant statistically. Bowel activity was similar in the two groups. Both drugs were free of toxicity. These investigations demonstrate that both lactulose and neomycin-sorbitol are effective in the treatment of chronic portal-systemic encephalopathy.

Aged↗

Relationship of plasma amino acids to nitrogen balance and portal-systemic encephalopathy in alcoholic liver disease.

Plasma amino acids were compared in three groups of patients with alcoholic liver disease including stable cirrhosis, acute alcoholic hepatitis without portal-systemic encephalopathy, and cirrhosis with encephalopathy. In addition, plasma amino acids were correlated with nitrogen balance in patients with acute alcoholic hepatitis and with clinical improvement in patients with encephalopathy. Significant differences in plasma amino acids within these groups were present. Plasma amino acids did not change with improvement in portal-systemic encephalopathy, and abnormalities of plasma amino acids did not prevent maintenance or attainment of positive nitrogen balance in patients with acute alcoholic hepatitis.

Acute Disease↗