L. Capocaccia

Branched-chain amino acids vs lactulose in the treatment of hepatic coma

A controlled study was carried out in two groups of 20 patients with cirrhosis of the liver and deep coma in order to compare the efficacy of intravenous branched-chain amino acid solutions in 20% glucose (group A) vs lactulose plus glucose in isocaloric amount (group B). There were 3 drop-outs from each group. Plasma amino acids and ammonia were assayed at fixed intervals throughout the 10-day observation period. Routine tests were assayed daily. Complete mental recovery was obtained in 70% of patients in group A and in 47% in group B. The difference was not significant, likely due to the lack of placebo group. With the exception of free tryptophan/all competing amino acids ratio, the modifications in plasma amino acid levels showed no correlation with the clinical course under either treatment. Ammonia, like free tryptophan, decreased significantly upon mental recovery, paralleling the clinical course throughout the study. In conclusion, branched-chain amino acids are at least as effective as lactulose in deep hepatic coma. It is suggested that branched-chain amino acids may reverse coma either by competing with brain entry of the aromatic amino acid or by metabolically decreasing free tryptophan and ammonia.

Isosorbide-5-mononitrate versus propranolol in the prevention of first bleeding in cirrhosis

BACKGROUND Hemodynamic studies have shown the efficacy of nitrates in reducing portal pressure in cirrhosis. We therefore studied the efficacy of isosorbide-5-mononitrate vs. propranolol in the prevention of first bleeding within a prospective controlled trial. METHODS One hundred eighteen cirrhotics with esophageal varices were blindly randomized to receive 20 mg of isosorbide-5-mononitrate three times a day (n = 57) or propranolol (n = 61) up to the maximum tolerated dose. Both groups also received ranitidine (150 mg/day). RESULTS The median follow-up was 29 months. Twenty-six patients dropped out (13 in the isosorbide group) because of poor compliance or complications unrelated to treatment. Eighteen patients died (9 in the isosorbide-treated group), 6 due to bleeding. The 1- and 2-year actuarial percentages of patients free of bleeding was 90.8% and 82.2% in the isosorbide-5-mononitrate--and 93.9% and 85.8% in the propranolol-treated groups, respectively (P = NS). These values are higher than those expected from the North Italian Endoscopic Club predicting scores. There were few major side effects in either group. The 2-year survival rate did not differ between the two groups (82.2% vs. 85.4%). CONCLUSIONS Isosorbide-5-mononitrate administered orally is a safe and effective alternative to propranolol in the prophylaxis of bleeding in cirrhosis.

Optimal nutritional indexes in chronic liver disease.

A population of 70 patients with liver cirrhosis, most of whom were nonalcoholic, was studied. Distribution of ideal body weight and body mass index was below the median of controls, but very few patients were below the cut-off points for normalcy. Distribution of triceps skinfold and arm muscle circumference was also below the median and, in most patients, was also below the cut-off points. Serum visceral protein concentrations and anthropometric parameters each were reciprocally correlated with one another, but no correlation was observed between visceral proteins and anthropometric parameters. Serum visceral proteins appeared to correlate better with the degree of liver damage than with the degree of malnutrition. Therefore, anthropometric parameters seem preferable to serum visceral proteins for the assessment of nutritional status in patients with liver cirrhosis.

Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. Incidence and risk factors

Forty-seven consecutive patients were prospectively evaluated to study the incidence of hepatic encephalopathy as well as modifications in the PSE index after TIPS. Various clinical, laboratory, and angiographic parameters were also recorded to identify risk factors for the development of post-TIPS hepatic encephalopathy (HE). Mean follow-up was 17±7 months. During follow-up, six patients died and one underwent transplantation. All other patients were followed for at least a year. Fifteen patients (32%) experienced 20 acute episodes of precipitated HE (hospitalization was necessary in 10 instances), and five patients (11%) presented a continuous alteration in mental status with frequent spontaneous exacerbation during follow-up. Both precipitated and spontaneous HE occurred more frequently during the first three months of follow-up. Moreover the PSE index was significantly worse than basal values one month after TIPS, thereafter returning to near basal values. HE was successfully treated in all patients but one who required a reduction in the stent/shunt diameter. Increasing age (>65 years) and low portacaval gradient (<10 mm Hg) were predictors of HE after TIPS. A gradual dilation of the stent/shunt should be performed to obtain a portacaval gradient >10 mm Hg to avoid an unacceptable rate of HE after TIPS.

Plasma amino acids imbalance in patients with liver disease.

The venous plasma amino acid patterns have been determined in 12 normal individuals and in 71 shunted and nonshunted cirrhotics in various grades of hepatic encephalopathy. The free amino acids have been determined by an amino autoanalyzer; the total and free tryptophan have been measured by a spoctrophotofluorimetric method. In 14 instances arterial plasma amino acid patterns have been measured simultaneously. High levels of aromatic and sulfurated amino acids and low levels of branched-chain amino acids have been constantly found in all cirrhotics. Methionine, phenylalanine, valine, leucine, tyrosine, and free tryptophan showed a statistical difference between controls and all other groups. These altered patterns did not correlate either with the grade or the evolution of the coma or with the presence of the surgical anastomosis. No statistical differences were lated with the grade and evolution of the hepatic encephalopathy was free tryptophan. The molar ratios between the amino acids sharing the same transport system across the blood-brain-barrier have been considered. A very good correlation with the grade of the mental disorder was found with the ratios free tryptophan/phenylalanine-tyrosine-methionine-valine-leucine-isoleucine and free tryptophan/branched-chain amino acids.

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. Conns 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 Conns index were observed. In conclusion, this study failed to confirm that short-term oral zinc supplementation improves chronic hepatic encephalopathy.

Effect of lactitol and lactulose administration on the fecal flora in cirrhotic patients.

We compared the effect of lactulose or lactitol on the fecal flora of 21 cirrhotic patients without hepatic encephalopathy. All were treated with an individualized disaccharide dose to achieve and maintain two semiliquid bowel movements per day. Stool pH and fecal flora were determined before and 10 days after stabilizing the cathartic effect. Increased counts of lactobacilli were obtained with both treatments. This increase, which was related to the decreased stool pH, was more constant with lactulose. In addition, lactitol decreased certain proteolytic bacteria such as enterococci and enterobacteria. Both total aerobic and anaerobic bacterial counts showed little quantitative variations with either treatment.

Glucose intolerance in liver cirrhosis

Abstract Glucose intolerance and hyperinsulinemia frequently occur in patients with chronic liver failure. To investigate the importance of glucose counterregulating factors, an oral glucose tolerance test was performed on 18 patients with compensated liver cirrhosis, matched for liver function tests and degree of portal hypertension, and 10 healthy controls. Blood glucose, immunoreactive insulin, C-peptide, immunoreactive glucagon, glucagon like immunoreactivity, growth hormone, cortisol and free fatty acids were determined in both groups at 30 min intervals for 240 min. Despite the similarity in the severity of liver damage five cirrhotic patients showed normal glucose tolerance, eight impaired glucose tolerance and five overt diabetes. Immunoreactive insulin was significantly higher in cirrhotic patients than in controls both before and during the oral glucose tolerance test. As basal C-peptide values were significantly higher and C-peptide/immunoreactive insulin ratio was significantly lower in cirrhotic patients than in the control subjects, both hyperproduction and hypodegradation seem to be responsible for the high insulin levels. Immunoreactive glucagon and cortisol showed no statistical differences between cirrhotic patients and control subjects whereas high basal growth hormone and free fatty acids values were observed in the cirrhotic group. Basal values and maximum increase or decrease of all the factors examined were tested by a correlation analysis with the blood glucose at 120 min and evaluated by a stepwise linear regression analysis. Only basal blood glucose, basal free fatty acids and immunoreactive insulin increment correlated significantly with blood glucose at 120 min. By the stepwise procedure these factors were found to account for 86% of the variance of the glucose level at 120 min. In chronic liver disease we failed to establish a pathogenetic role of hormones involved in the glucose counterregulating system. Free fatty acids may play an important role in glucose intolerance in chronic liver failure.

Plasma and Cerebrospinal Fluid Amino Acid Patterns in Hepatic Encephalopathy

Plasma and cerebrospinal fluid amino acid levels were measured in 12 cirrhotic patients in grade 0 hepatic encephalopathy and 17 in grade 3–4 hepatic encephalopathy. In 5 of these patients amino acid determinations were performed during the evolution of the encephalopathy. No correlation was found between the degree of hepatic encephalopathy and the plasma amino acid imbalance. In the CSF of cirrhotic patients without encephalopathy, a significant increase was found in nearly all amino acids, including those known to not easily cross the blood-brain barrier; this suggests the presence of a nonspecific modification of the blood-brain barrier permeability. In patients with severe hepatic encephalopathy, the further increase only in cerebrospinal fluid aromatic amino acids and methionine levels suggests the presence of a selective stimulation of the neutral amino acid transport system across the blood-brain barrier. Finally, the good correlation between glutamine and the sum of neutral amino acids found in the cerebrospinal fluid only in the presence of encephalopathy supports the hypothesis that brain glutamine may stimulate neutral amino acid transport across the blood-brain barrier.

Total and individual free fatty acid concentrations in liver cirrhosis

The finding of high plasma free fatty acid (FFA) levels in cirrhotic patients has been attributed either to decreased hepatic clearance or to enhanced fat mobilization. To better clarify these hypotheses, total and individual FFA and glycerol levels were determined in 21 cirrhotic patients with different degrees of hepatocellular damage (evaluated by liver function tests), portal hypertension (evaluated by endoscopy and clinical signs), and nutritional status (evaluated by anthropometric and biohumoral parameters) and in 10 age- and sex-matched healthy subjects. Glucose tolerance and insulin and glucagon levels were determined in all individuals. Well-nourished and malnourished patients were identified within the cirrhotic group. Plasma FFA and glycerol concentrations were well correlated (r = 0.47, P less than 0.05), levels being significantly higher in cirrhotic individuals than in controls (746.6 +/- 46.29 SE v 359.22 +/- 40.82 mumol/L, P less than 0.001 for plasma FFA; 150.1 +/- 3.12 v 82.5 +/- 9.2 mumol/L, P less than 0.01 for glycerol). Plasma FFA and glycerol showed no correlation with the liver function test results or portal hypertension parameters. Interestingly, plasma levels of FFA and glycerol were influenced by the nutritional status, significantly higher FFA levels being observed in the well-nourished than in the malnourished patients (842.5 +/- 47.5 v 563.4 +/- 78 mumol/L, P less than 0.005). Furthermore, a positive correlation was found between plasma glycerol level and percentage of triceps skinfold (r = 0.45, P less than 0.05). No correlation was found between plasma levels of FFA or glycerol and glucose tolerance, insulin and glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)